OBR Blog Entries

Ins and Outs of Compensation in the Multi-Disciplinary Setting

2010-02-08T09:17:00.000-08:00

Ins and Outs of Compensation in the
Multi-Disciplinary Setting

By John Watson

By having all relevant caregivers in one room prospectively reviewing cases, multidisciplinary cancer clinics make it possible to impact patient care from the very beginning. Getting all those separate caregivers into the room in first place, however, remains a significant challenge. At the 2009 Cancer Center Business Summit in Dallas, Texas, attendees were given an overview of the different ways of incentivizing physicians to dedicate the time and energy required in the multidisciplinary setting.

Physician Compensation Models
According to Mano Mahadeva, CPA, executive director of North Texas Operations at US Oncology, there is no perfect model for physician compensation. However, all good models share certain characteristics, such as promoting teamwork amongst colleagues, being easily understandable and flexible enough to accommodate new specialties.

There are three basic compensation models: an equal split model, a full production model, and a hybrid of these two. Equal split models have the advantage of being easy to understand, and since everyone receives the same payment, do not require complex formulas. However, this payment method can be seen as a disincentive to productive physicians.

“If I see 20% less patients than my colleague, well that could be an issue in the practice,” said Mahadeva.

Conversely, full production models reward physicians for increased efforts, but rely on complex, potentially time-consuming formulas to do so. Additionally, this model can create an overly competitive environment.

Hybrid models are the most popular, according to Mahadeva, because the full production element recognizes added value, while the equal split aspect compensates for other issues. Splits for this model are usually in the range of 60/40 to 70/30.

Choosing Models
Bruce Cutter, MD, a medical oncologist and hematologist at Cancer Care Northwest (CCNW), shared his group’s experience choosing between these different models. CCNW was a group of six medical oncologists with a compensation model based on gross productivity, until the late 1990s when they decided to add additional specialties.

“We couldn’t do things based on gross revenue any longer, because the contractual allowances for each specialty are all different,” said Cutter. “Medical oncologists might get 50 cents for every billed dollar, while radiation oncologists get 28 cents, and surgeons get 25 cents.”

CCNW eventually settled on a fairly simple model using a 60% productivity/40% equal share split of practice income. This system is applied to the specialties within the practice based on total specialty professional net revenue, taking into account varying contractual allowances. Income is then split within each specialty based on the chosen systems of the doctors in these subgroups. For example, the medical oncologists decided to split their pool of money based on productivity, while the radiation oncologists are sharing their money equally.

Models for Hospital-Employed Groups
Doctors looking into hospital-based medical groups will typically encounter a handful of specific features to any potential employment offer, according to Jessica Turgon, MBA, senior manager at ECG Management Consultants, Inc. There continues to be a component of a base salary within a compensation plan, whether it is 50% or 80%, but it is now offered with an incentive payment based on a production component using relative value units related to a physician's work (WRVUs). However, as hospitals “also want to hold physicians responsible for some of the expense categories that they wouldn’t get under a WRVU model,” said Turgon, they’re also implementing an expense or budget component (i.e., clinical expenses). Many hospitals also use quality measures to incentivize physicians—where performance as a group or system may also be measured and rewarded.

Lastly, Mark Krasna, MD, medical director of the Cancer Institute at St. Joseph Medical Center in Towson, Maryland, took attendees through the four employment models for hospital-based cancer centers.

The full-time employment model, in which doctors are employed by the cancer center, is the simplest model from a legal standpoint; however, it is difficult to convince some physicians to come on as full-time employees.
In the private practice model, the practice is integrated into the cancer center, so that all patients are seen in the multidisciplinary space. This is also considered a simple model for hospitals, and doctors are willing to participate because it allows for increased patient volume and improved practice through prospective case review.
Joint venture models, in which the cancer center owns the facility jointly with a private practice, are more common with radiation oncology and surgical centers, and less feasible for medical oncology.
The part-time employed/contracted full-time equivalent model, in which doctors are paid at fair market value according to the Medical Group Management Association, is the most legally complex of the four and requires doctors to find a way to be efficient operating only in set block of time.

According to Krasna, no matter what system an oncologist chooses to join, simply being part of a multi-disciplinary care system can yield significant rewards, not only in revenue but in improving patients’ quality of care.

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Cancer Highlights of 2009

2010-01-19T10:42:00.000-08:00

Cancer Highlights of 2009

1) Biggest Biotech Deal To-Date
After an eight-month battle, Roche finally gained control of its longtime U.S.-biotech partner Genentech in a $46.8 billion takeover deal to reinforce its leading position in cancer medicines. Genentech's board and shareholders ultimately accepted the Swiss drug maker’s offer of $95 a share for the 44 percent of the company it didn't already own; the buyout was completed in March and Roche will rebrand its U.S. medicines as Genentech, including non-biotech drugs. In addition, Roche will drop its long-standing membership in the PhRMA (Pharmaceutical Research and Manufacturers of America) trade group in favor of the Biotechnology Industry Organization (BIO).

2) USPSTF Breast Cancer Screening Recommendations Stir Controversy
Controversial new breast cancer screening guidelines issued in November by the U.S. Preventive Services Task Force (USPSTF) dropped widely-held guidance that women get routine annual mammograms starting at age 40. Instead, the guidelines now advise women ages 50 to 74 could be screened every other year, while those in their 40s should make an individual decision after talking with their doctors. The new guidelines shook up the clinical norm on breast cancer screening and ignited a public debate that dominated the news as 2009 came to a close. On the heels of the task force’s announcement, the American College of Obstetricians and Gynecologists (ACOG) announced revised recommendations for Pap tests, saying young women should begin getting the cervical-cancer screening test at a later age and at less frequent intervals than previously recommended.

3) Pricey Cancer Drugs—Here to Stay?
With Allos Therapeutics’ newly approved lymphoma drug Folotyn™ reported to cost $30,000 per month, and GlaxoSmithKline’s new drug Arzerra™, approved for chronic lymphocytic leukemia, reported to cost up to $98,000 for a six-month treatment course, cancer drug costs once again made major headlines. Drug makers have primarily defended the cost of these expensive drugs for rare cancers, and other high-priced cancer treatments, by saying that they fulfill an unmet need for patients who have either few or no treatment options. But critics say that the therapies don’t provide enough benefits to patients to merit the high prices. In the U.K. in November, the National Institute for Health and Clinical Excellence (NICE) issued draft guidance against recommending Nexavar® for advanced liver cancer for reimbursement on the National Health Service (NHS) saying the price being asked by the drug’s manufacturer Bayer was simply too high compared to “better value cancer treatments.” Although NICE indicated it had changed its approach to appraising high cost treatments—with more treatments which could extend life for terminally ill patients being recommended—the advisory body seemed to have held its ground on allowing coverage for a number of the more expensive cancer therapies during 2009. Late in the year, for example, it turned down the use of Avastin® for the treatment of metastatic colorectal cancer, saying that the drug “did not represent a cost-effective use of NHS resources.”

4) Health Care Reform’s Impact on Oncology
The future of the U.S. cancer care delivery system and access to high quality cancer care for patients was increasingly jeopardized in 2009 due to proposed cuts for CY2010 from the Centers for Medicare and Medicaid Services (CMS). But influential cancer groups including ASCO, COA, US Oncology, ASTRO and others voiced their concern with legislators and pulled off several key victories which should impact oncologists and cancer patients more positively than anticipated earlier in the year when a final health care bill is agreed upon by both the House and Senate in early 2010.

Health care reform legislation is estimated to spend between $850 billion and $1 trillion in the industry funded by new taxes, and cuts to insurers, PhRMA, hospitals and other providers, with lessened cuts to core businesses of medical oncology, radiation oncology, office-administered drugs and PET/PET-CT imaging.

The President signed the law that will create a short term patch to Medicare’s Sustainable Growth Rate (SGR) formula, averting the 21 percent cut to Medicare physician payments from taking place for two months. The patch runs through February 28, 2010. It is anticipated that future legislation will permanently eliminate or delay the built up Medicare physician payments cuts currently required by the Sustainable Growth Rate (SGR) formula.

The legislation expands the privately-insured patient population in need of cancer care, eliminating pre-existing condition exclusions and rescissions.

The removal of prompt pay discounts of up to 2 percent from the Average Sales Price (ASP) calculation, not included in either the House or Senate health care bills, is unlikely to be included in final legislation. But oncologists' felt they had made progress with legislators on the issue.

In the final rule issued in October, CMS eliminated consultation codes entirely, in both the inpatient and outpatient/office setting. According to ASCO, eliminating consultation codes will disadvantage physicians, like most oncologists—a recent analysis suggests that medical oncologists will experience a decrease of 28 percent in Medicare reimbursement as a result. ASCO supported an amendment to the Senate bill which would delay the elimination of consultation codes for one year. The amendment could come up again when the House and Senate bills are reconciled.

It's likely that a provision requiring insurance companies to cover routine care costs associated with a clinical trial will be a part of the final legislation crafted.

Although the House passed a bill including a new Medicare benefit that will pay physicians to have advance care planning/end-of-life counseling discussions with patients, the Senate's version of the bill did not. It's uncertain if the provision will be included in the final bill.

Within health care reform legislation, oncology practices are likely to benefit from the creation of pilot Accountable Care Organization (ACO) programs for Medicare and Medicaid providers. A provision was included in the House bill that will allow oncologists to form ACOs and share in savings that accrue to Medicare through the use of evidence-based pathways, disease management and advance care planning. US Oncology, for one, is working to ensure that the provision remains in the final health care legislation enacted in 2010.

5) Personalized Medicine Makes Strides
In big clinical findings at ASCO, a Phase 3 study of Herceptin® significantly prolonged the lives of patients with HER2-positive advanced stomach cancer when combined with standard chemotherapy. In advanced melanoma patients with a mutated BRAF gene, patients showed significant tumor shrinkage when given an experimental drug being co-developed by Roche and Plexxikon known as PLX4032. Data from a small, early-stage study indicated that the drug prevents progression of the disease for six months. In other news, Genomic Health’s Oncotype DX® colon-cancer test, based on an analysis of seven different genes found in colon-cancer tumors, indicates whether patients are at low, intermediate or high risk of having the disease return after it is surgically removed. And in March of 2009, cancer doctors at Massachusetts General Hospital announced that genetic testing would become a commonplace aspect of treatment for nearly all new cancer patients within a year. Doctors plan to screen for 110 abnormalities, carried on 13 major cancer genes, that predict whether drugs on the market or in development might thwart a patient’s tumor.

6) 2009 Clinical Trial Successes & Failures

Successes:

A pivotal Phase 2 study of T-DM1 showed that the experimental drug shrank tumors in 33 percent of critically ill breast cancer patients whose disease no longer responded to treatment with either Herceptin or GlaxoSmithKline's Tykerb® and patients went an average of 7.3 months before their tumors began to grow again.
In advanced head and neck cancer, Erbitux® increased survival by 20 percent when added to initial chemotherapy, compared with chemotherapy alone. Researchers also saw a 46 percent increase in progression-free survival.
Data from a Phase 3 study of Provenge™ demonstrated that the prostate cancer vaccine extended the average survival of patients by four months compared with a placebo, nearly twice as long as the best available chemotherapy, and increased three year survival by 38 percent. The FDA is scheduled to make an approval decision on the drug on May 1, 2010.
OncoGenex Pharmaceuticals’ new cancer drug, OGX-011, extended the survival of patients with advanced prostate cancer by almost seven months when combined with Taxotere®, based on results from a Phase 2 study.
Eli Lilly’s Alimta® increased overall survival after standard chemotherapy by 50 percent for advanced lung cancer patients in a large, international trial, establishing the drug as a new standard of care in maintenance therapy for advanced nonsquamous non-small cell lung cancer.
Onyx's carfilzomib significantly reduced multiple myeloma in 45 percent of patients who didn’t respond to as many as three previous therapies in a Phase 2b study.
Sanofi-aventis/BiPar’s investigational PARP1 inhibitor, BSI-201, improved median overall survival from 7.7 months to 12.2 months in patients with metastatic triple-negative breast cancer (mTNBC) when added to gemcitabine and carboplatin (GC), based on updated overall survival data presented at SABCS.

Failures:

Avastin failed the large, closely watched C-08 trial as an adjuvant treatment in early-stage colon cancer. But the year was hardly a total clinical washout for Avastin–it won FDA approval as a single agent for previously treated glioblastoma, the first new drug for the disease in a decade, and was also approved for metastatic renal cell carcinoma in combination with interferon.
Poniard’s chemotherapy drug picoplatin failed to significantly prolong survival in patients with advanced small cell lung cancer based on pivotal Phase 3 study results disclosed in November, dashing hopes for the company’s initial FDA approval filing. Picoplatin then showed some moderate success in a colon cancer trial.
Synta announced disappointing preliminary results from the Phase 3 Symmetry trial of elesclomol in metastatic melanoma when the study's primary endpoint of progression free survival (PFS) failed to show statistical significance except in a small subgroup of patients. Trials of elesclomol were halted earlier when a higher death rate among patients taking the experimental drug was observed.
Preliminary data from Genta’s Phase 3 trial of Genasense® in advanced melanoma failed to show a statistically significant benefit for its co-primary endpoint of progression-free survival. Data for the other co-primary endpoint of the trial, overall survival, was still too early to evaluate in 2009.
Pfizer halted a late-stage trial of figitumumab in non-small cell lung cancer, after an analysis showed that it would be unlikely to meet the main goal of improving overall survival when added to two older therapies—paclitaxel and carboplatin—compared with the standard therapy of paclitaxel plus carboplatin alone. Pfizer stopped enrolling patients in the study several months earlier due to a greater number of negative events in the trial’s figitumumab arm, including death.

Some of the more high-profile drugs that were turned down for FDA approval and/or which received a no-go from the Oncologic Drugs Advisory Committee (ODAC) included:

An FDA advisory panel rejected Roche/OSI Pharmaceuticals’ Tarceva® as a first-line maintenance treatment in non-small cell lung cancer, saying the treatment benefit was modest compared with other available therapies (Tarceva’s approval fate should be decided by April 18, 2010, its PDUFA date);
Vion’s Onrigin™ as a single agent for patients 60 years of age or older with poor-risk acute myelogenous leukemia (AML);
GTx’s Acapodene® for the reduction of fractures in men with prostate cancer on androgen deprivation therapy (ADT); and Genzyme’s Clolar® for use in adult patients with acute myeloid leukemia (AML).

Click on the image below to view the table of 2009 FDA APPROVALS OF ANTI-CANCER AGENTS:

Year End Financial Summary

Click on the image below to view the table of 2009 MARKET PERFORMANCE:

Click on the image below to view the table of 2009 TUMOR TICKER TOP 5 WINNERS & LOSERS:

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No Magic Bullets for Drug Price Reform: Notes from ASH and SABCS

2010-01-06T10:56:00.000-08:00

No Magic Bullets for Drug Price Reform:
Notes from ASH and SABCS

By Neil Canavan

ASH: The High Cost of an Unmet Need
Andrew Pollack, a journalist from the New York Times, set the 2009 ASH in motion with his front-page, opening-day article, “A Fortune to Fight Cancer”, which highlighted the record-setting price of Folotyn. Approved in September ‘09, Folotyn, manufactured by Allos, Westminster, CO, is indicated for the treatment of peripheral T-cell lymphoma. According to clinical trials, the drug is adept at shrinking tumors, and thereby extending progression-free (but not overall) survival—so, to be clear, the patient may well be more comfortable, but will not live longer. And the price? It’s roughly $30k a month.

The article appeared just as several Allos/Folotyn posters were being presented at ASH, and poster presenters hastily deferred all questions from the press to the nearby-stationed, Monique Greer, Vice President of Allos’ Corporate Communications. “Well, it did generate a lot of awareness for a small company,” Greer observed, in the sense that there’s no such thing as bad publicity. “But once we got past the headline it enabled us to get into the discussion about how rare this disease state really is, and the fact that it has a very poor prognosis.”

Greer also suggested an angle to the economics concern: the drug requires little of supportive care; it’s administered on an outpatient basis; and only requires a few minutes in an I.V. push. She further pointed out that doctors were more interested in the drug’s mechanism of action and response rates, rather than its price. What Greer says she hears from patient advocates is that they understand what’s at stake in drug development.

Judy Jones, President of the Cutaneous Lymphoma Foundation, is by no means a cheerleader for drug prices based on whatever the market will bear, but in a telephone interview she was sympathetic to certain arguments. “We’re dealing with a new treatment for a disease that has no FDA approved treatment. Until this drug came along these patients didn’t have anything. Do I wish that these [new] drugs were cheaper? Absolutely. But I don’t know how to determine how much is too much, and I don’t want to threaten new drug development.”

A day after Pollack’s article appeared in the Times, a seemingly prescient talk at ASH, titled, “The Cost of Health Care: Balancing a Patient's Right to Care with the High Cost of Some Drugs and Procedures” suggested that the issue of drug pricing might be addressed. But that was not the case. What the speaker, economist Paul Ginsburg, President of the Center for Studying Health System Change, Washington, D.C., did discuss were those cost-drivers common to the healthcare system as a whole where, in general, many highly effective drugs are now, or soon will be, off-patent.

This is not the case, of course, for cancer treatments. “I quickly realized during the course of the meeting that in oncology, one of the biggest issues is drug pricing,” he said, and he’s wary of the competing interests in trying to bring down costs. “All spending is someone else’s income,” Ginsburg said, adding that oncologists have long standing conflicts of interest because they sell drugs directly to the patient, and are, in fact, competing with pharmacies when it comes to oral vs. I.V. medications. “In the industry these are called self-referral incentives,” he said, “like if a physician orders a CT scan, and s/he just happens to also own a CT scanner.”

SABCS: The Race Heats Up
Healthcare reforms are coming, to be sure; but just how elegant or crude the reforms will be may depend largely on the body of the reformers. “The oncology community would do itself a favor by taking this issue seriously instead of constantly excepting the idea that anything that works at any price has to be good,” said Hal Burstein, MD, PhD, Dana-Farber Cancer Institute, Boston, MA. His comments came after the SABCS presentation of promising data for a combination treatment of Herceptin (trastuzumab) and Tykerb (lapatinib) in the setting of metastatic breast cancer (Abst. #61)—a regimen that will run a minimum of $15,000 a month, for a payoff of just over four months of increased survival.

Burstein is also concerned with the very language used in the reporting. He responded to the headline-reporting of data for the so-called PARP inhibitor, BSI-201. “The Times said, ‘drug improves survival’, which is true, it improves by two months, meaning, May vs March.” But some patients misunderstood the language, thinking they now had a shot at an actual cure, which could easily drive demand for something that is only minimally effective.

Also reported at SABCS were results from Avastin’s AVADO and RIBBON trials, where success was measured, as with Folotyn, as gains in progression-free survival. Matthew Ellis, MB, PhD, Director of the Breast Health Program, Washington University and Barnes-Jewish Hospital at St. Louis, MO, said “we need to be careful about approving drugs that don’t improve survival, yet cost $50k to $60k a year.”

Gabriel Hortobagyi, MD, Director of the Breast Cancer Research Program at the M.D. Anderson Cancer Center, Houston, TX, concurs: “Multiply [that] by the number of breast cancer patients out there, and pretty soon we’re talking about real money.” And money begets money. Profits are put back into research that hopefully will lead to more drugs, and more profit. But therein lies part of the problem. “In oncology,” said Hortobagyi, “we do a huge amount of research on drugs, and very little research in biomarkers,” the biological signals that could tell you if the drug is working, or, before the drug is even given, if it even has a chance of working. He also said that “to do healthcare reform right, competitive efficiency [of treatments] has to be provided with a reasonable funding mechanism.”

As the clinicians wait for these assays to determine who might actually benefit from a given drug, the philosophical task of defining benefit must be addressed. “That is the debate to be had by everyone,” asserts Mothaffar Rimawi, MD, Baylor College of Medicine, Houston, TX. The community of physicians needs to comment on it, and the community of patients and patient advocates also need to comment on it. “What is the dollar value we put on a month gained, or the quality of a life briefly improved? This is a very sensitive discussion. Is your position that of having a loved one who is a patient, or are you a policy maker who has a limited number of dollars to stretch?”

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Pipeline Online™ Updates 12/09

2009-12-09T09:52:00.000-08:00

Pipeline Online™ Updates 12/09

ASH and SABCS are good examples. We get barraged with information about oncology products and clinical progress, making maintaining our Pipeline Online database challenging. However, we’re in a unique position because we monitor all this news as we prepare and deliver OBR daily each day to stay ahead of all the information. And because we already have an extensive database, probably the most extensive there is, at this point it just takes good discipline to maintain and update our database as the news comes out.

Because many of our readers ask how we maintain the Pipeline Online database, we thought we’d share a recent example with you. If you follow the link below you’ll see a recent spreadsheet that we uploaded to maintain the database.

blog.oncbiz.com_PipelineOnline1209.pdf

ASH '09 Sneak Preview

2009-11-30T10:33:00.000-08:00

ASH '09 Sneak Preview

Immediately below is an American Society of Hematology Sneak Preview highlighting some of the more compelling data announcements at this year’s ASH meeting. The information below is brought to you by the publisher of The Medical Technology Stock Letter (MTSL), John McCamant, (www.bioinvest.com). The information published here is not a recommendation, and is provided for informational purposes only.

Although abstracts for the American Society of Hematology (ASH), taking place in New Orleans, December 5-8 have been released, they fail to offer any major insight into the widely anticipated Celgene (CELG) MM-015 study on Revlimid. Both Incyte’s (INCY) and Onyx’ (ONXX) abstracts were of particular significance; and we expect INCY's JAK-2 inhibitor, INCB018424; and ONXX’ carfilzomib (Proteolix) to both deliver game changing data. In fact, INCY’s 18424 has already been significantly validated by the huge partnership inked with Novartis last week. The key for these names will be presenting fresh Phase 2 data that will instill confidence in both company’s on-going Phase 3 programs. Other MTSL recommendations that will be at ASH include ImmunoGen (IMGN) and Allos (ALTH).

Allos has announced that four abstracts from studies of Folotyn were accepted for presentation. Presentations will summarize new analyses of data and updated efficacy results from the company’s pivotal PROPEL study, which served as the basis for the FDA’s accelerated approval of Folotyn on September 24, 2009, for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). In addition, there will be a poster summarizing results of a Phase 1 study of Folotyn in combination with gemcitabine in patients with relapsed or refractory lymphoproliferative malignancies, and an oral presentation highlighting results of a multicenter, dose-finding study of Folotyn in patients with cutaneous T-cell lymphoma (CTCL). The posters are important as they are part of the process of educating oncologists about the benefits of Folotyn. But probably most important from a stock point of view is that potential partners/acquirers will be in attendance. The drug remains unpartnered and has to be on the radar screens of many companies that are looking for new drugs. Given the recent INCY/Novartis deal we feel that some of the spurned bidders for INCY’s drug candidate are now exploring a deal with ALTH.

Celgene. Recently, it was reported that CELG has been having ongoing conversations with the FDA and EMEA regarding the MM-015 trial. It appears that the company might be able to present unblinded data at ASH from all 3 arms from MM-015 study based on 50% events. Positive data would be important as the top-line results announced last July demonstrated a statistically significant improvement in progression-free survival over treatment with chemotherapy alone. The primary concern from Wall Street is that the benefit of Revlimid maintenance won't outweigh Revlimid induction, as more Revlimid is used in maintenance therapy.

ImmunoGen has momentum going into ASH as they recently reported encouraging clinical data from its IMGN901 drug development candidate for the treatment of Merkel cell carcinoma (MCC). These findings were reported at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. A total of six patients with MCC have received IMGN901 to date. All of these patients had received prior chemotherapy regimens for their cancer and entered the clinical trial, Study 002, with metastatic disease. Two of these six patients had a marked, objective response to treatment with IMGN901, while a third patient had clinically relevant stable disease for this patient population

IMGN901 has been designed to kill cancer cells that express CD56, a protein. It consists of a CD56-binding antibody with the company’s potent cancer-cell killing agent, DM1, attached to it using an engineered linker. IMGN901 is a potential treatment for MCC, small-cell lung cancer (SCLC), multiple Myeloma (MM), ovarian cancers and other CD56+ tumors.

IMGN will have additional data at this week’s ASH as IMGN901 is also being evaluated for the treatment of CD56+ MM. Study 003 evaluates the compound when used as a single agent to treat MM patients that have progressed on prior therapies despite being heavily treated (mean prior therapies=6). The maximum tolerated dose was recently established in this trial as well, and patient enrollment is underway in the expansion phase. Some of this data will be presented at next month’s ASH meeting. Study 005 will evaluate IMGN901 for MM when used in combination with Revlimid and dexamethasone. This trial is expected to start later this year.

Also at ASH, we will see the first dataset for SAR3419, a CD19-binding antibody with the DM4 payload attached. The drug candidate showed impressive efficacy (3CR/2PR) in a Phase 1 trial in Rituxan-refractory NHL (mean prior therapies = 4). SAR3419 is licensed to Sanofi and represents another drug development candidate that has the potential to add to the company’s overall value, as the IMGN investment story is clearly more than just T-DM1.

InCyte The Phase 1/2 data for INCB18424 in polycythemia vera (PV) and essential thrombocytosis (ET) will show treatment affects after three months of dosing for all patients. The abstract shows 34 patients treated for three months, with 20 having been treated for six months. 94% of these patients had a PR or CR. Exaggerated JAK2 signaling is believed to play a dominant role in PV and ET by driving unchecked differentiation and proliferation of red blood cell and platelet precursors. Thus, the endpoints will focus on the reduction in cell count of red blood cell and platelets, splenomegoly, and disease symptoms such as pruritis. We expect positive results based on management sentiment and the higher frequency of JAK-2 mutation in PV and ET than in myelofibrosis (MF), an area in which 424 has already shown proof of concept. Additionally, INCY will provide an update of the ongoing Phase 2 study in MF. The average exposure to drug is at 1.5 years in this trial, with at least 80 patients having been treated for that long. The other oral presentation will focus on early Phase 2 testing being done at the M.D. Andersen cancer center of 424 in refractory AML patients.

We expect 424 to be one of the big winners at this year’s ASH as the combination of data is very impressive. We also think that many analysts have been underestimating the market potential for 424 by focusing on the MF market which is 14,000 patients in the U.S. While 14,000 patients is a decent sized market opportunity, the markets for PV (95,000) and ET (80,000) in the U.S. have the potential to get Wall Street analysts to significantly increase their estimates for 424’s potential. In addition, INCY estimates these same markets in Europe are 1.5 times larger than in the U.S. Thus, the combination of the three diseases in the U.S. and Europe adds up to a substantial cancer opportunity. The higher frequency of JAK-2 mutation in PV and ET patients than in MF also adds to our confidence that the data will be positive. We expect INCY to have a strong presence at ASH and the stock price to move higher.

Onyx has announced nearly 20 presentations at ASH evaluating carfilzomib and ONX 0803 (SB 1518) in hematological cancers. Among the data presentations are four oral and seven poster presentations highlighting data from the carfilzomib development program in patients with relapsed and refractory multiple myeloma (MM). Carfilzomib data highlights include:

Updated Results of Bortezomib-Naive Patients in PX-171-004, an Ongoing, Open-Label, Phase II Trial of Single-Agent Carfilzomib (CFZ) in Patients with Relapsed or Refractory Myeloma (MM)
PX-171-004, an Ongoing Open-Label, Phase II Study of Single-Agent Carfilzomib (CFZ) in Patients with Relapsed or Refractory Myeloma (MM); Updated Results from the Bortezomib-Treated Cohort
Phase Ib Multicenter Dose Escalation Study of Carfilzomib Plus Lenalidomide and Low Dose Dexamethasone (CRd) in Relapsed and Refractory Multiple Myeloma (MM)
Carfilzomib (CFZ), a Novel Proteasome Inhibitor for Relapsed or Refractory Multiple Myeloma is Associated with Minimal Peripheral Neuropathic Effects

ONX 0803 (SB1518) data highlights include:

Phase I Study of the Novel Oral JAK-2 Inhibitor SB1518 in Patients with Relapsed Lymphoma: Evidence of Clinical and Biological Activity

The company has done a very good job of creating a pipeline behind Nexavar and this year’s ASH is their chance to show it off. We seen some of the carfilzomib data before the acquisition and have been impressed. The ability to work in refractory MM is very important as it is the best shot at gaining approval given the multiple choices front-line MM patients already have. The refractory market is larger than one might expect as unfortunately all MM patients will eventually relapse as they become refractory to drug therapy.

GenVec receives Orphan Drug status for TNFerade

2009-11-04T11:05:00.000-08:00

In a new feature for OBR readers, we will occasionally get updates relevant to recent oncology headlines or upcoming oncology events from John McCamant, publisher of The Medical Technology Stock Letter (www.bioinvest.com). The information published here is not a recommendation, and is provided for informational purposes only.

GenVec’s stock is up as much as 25% this morning on news that the FDA has given “Orphan drug” designation to TNFerade for the treatment of locally advanced pancreatic cancer. The most important aspect of Orphan drug status is that it provides seven years of market exclusivity after a drug is approved. The news serves as a reminder that TNFerade is a Phase 3 cancer drug development candidate that will address a protected market. Orphan drug status also makes it easier for a potential partner to pull the trigger as they can view TNFerade as a having at least one protected market opportunity. The drug candidate is also being tested in several other hard to treat cancers; head and neck, rectal, and esophageal. When one combines these markets together, it makes it easier to see how a potential partner would be able to leverage the technology to create multiple revenue streams. We met with management last week at the BIO Investor conference and the company is clearly growing more optimistic with the TNFerade PACT trial finally maturing. A planned interim analysis is expected to occur this quarter when the 184 events (deaths) have occurred in the trial. The data then would be announced roughly 10-12 weeks later, after the data has been cleaned, which we would expect to occur sometime during the first quarter of 2010. While we do not expect the trial to be stopped prematurely, once the interim has been passed smoothly, a partnership may materialize before PACT concludes. Our optimism for a partnership is based on two points. The first is the next interim look should provide additional info on TNFerade’s safety and efficacy making it a more desirable partnership candidate. Second, is the fact that there remains a dearth of late-stage cancer drug development candidates that are unpartnered. Thus, our confidence is growing that the combination of these factors may lead to a partnership for TNFerade before PACT concludes. The stock has periodically traded as high as $1.00 and as of 2PM EST was trading at $0.89.

Pipeline Online™ Updates

2009-06-29T21:04:00.000-07:00

What company is advancing in cancer immunotherapy? Who just announced a new Phase 3 study in patients with advanced inoperable breast cancer? What drug missed its goal in a mid-stage study of acute myelogenous leukemia (AML)? These are just some of the questions that can be answered by going to Pipeline Online at www.oncbiz.com.

Over a dozen new oncology-focused companies and roughly 40 new pipeline products have been added to Pipeline Online since our May launch. This is in addition to the hundreds of updates we’ve been keeping track of to what we believe is the most comprehensive oncology pipeline database widely available on the Web.

With that said, a few of the noteworthy additions and updates that we’ve made to the database include:

Biovest International—a company that is contributing to the advancement of cancer immunotherapies/vaccines. Featured at an ASCO Plenary Session, Biovest presented data on their immunotherapeutic vaccine -- BiovaxID™ -- in Phase 3 development for follicular non-Hodgkin’s lymphoma.

After high-profile setbacks to immunotherapeutic companies such as Favrille, Cell Genesys and Genitope, Biovest International is renewing interest in the field that many feel is making a “comeback” since the positive data delivered by Dendreon/Provenge^® earlier this year.

Following the lead on immunotherapeutics, other biotech firms updated in Pipeline Online include Merck/Oncothyreon’s Stimuvax^®, and Apthera’s NeuVax™. Merck and Oncothyreon announced a new Phase 3 study of Stimuvax in patients with advanced, inoperable breast cancer while Apthera recently received SPA approval for its planned Phase 3 study of NeuVax in advanced breast cancer.

That brings the total in the Pipeline Online database to 8 immunotherapies in Phase 3 development ranging in tumor type from lymphoma and melanoma to prostate, head and neck, liver, and lung.

In addition to the immunotherapy class in our database, we have over 350 drug classes to search, more than 160 companies listed, 40 tumor types recognized, and over 500 products.

Other news to be gleaned from the database includes Cephalon announcing lestaurtinib missed its goal in a mid-stage study of AML. The company stated the drug did not improve survival compared with standard chemotherapy.

Also updated is Immunogen’s pipeline after the announcement that they would discontinue a Phase 2 study of IMGN242 in gastric cancer due to slow progress.

On the other hand, Oncogenex recently announced that they are set to proceed with its Phase 3 study of its lead product candidate, OGX-011, in patients with hormone refractory prostate cancer.

Clavis Pharma, another new addition to Pipeline Online, announced a registration trial is being planned based on positive results from a Phase 2 study of elacytarabine in patients with late-stage AML.

One of the key elements to the continued success and usefulness of Pipeline Online is the dedication we have to maintaining the accuracy and depth of information. We do this through our constant monitoring and endless pursuit of all oncology news, events, and information that we use to produce OBR daily, Oncology Business Review, and our newest product, OBR green.

To get more details on all these resources, please visit our Web site at www.oncbiz.com.

ASCO Sans Chotchkies

2009-06-09T10:39:00.000-07:00

By Neil Canavan

This year’s annual meeting of the American Society of Clinical Oncology (ASCO) is the first to be held since the new PhRMA guidelines regarding pharmaceutical industry giveaways went into effect—which is to say, it was the first ASCO without toys. Gone were the wind-up mouse models, squeezable brain-shaped stress balls, twisty-puzzle molecules, travel kits, tote bags and penlights; and gone too, in fact, were even the handy (branded) pens. In brief, it was the first ASCO sans chotchkies.

The ban of all such items, frivolous and otherwise, dates to January 1st of this year, beyond which time pharma companies were to voluntarily withdraw any offers of anything which might be construed as exerting influence, or currying favor with healthcare providers. This prohibition includes amusements both macro (trips, events, dinners) and micro (notepads, calendars, cups) and even veers into educational activities such as CME.

While the potential impact on educational programs has not been fully realized, the effect of banning toys and entertainment was immediate: there were times when the ASCO exhibit hall looked like a ghost town. “It’s a very different world out there,” intoned one grim-faced drug rep, as he gazed beyond the confines of his sparsely populated booth.

Indeed, as I toured the exhibit hall, the jovial, near carnival barker-like drug rep of old was not to be found and in his stead was the serious, the sedate, and the concerned: “I kid you not, I’ve got ten cases of mousepads in my basement. What am I suppose to do with this stuff?” Perhaps the glut of giveaways has spilled over onto eBay where a search for pharmaceutical pens yielded more than a hundred auctions. If this is PhRMA guidelines related, I do not know.

Only the inexperienced were at ease. An ASCO first-timer stood serenely by his supply of renal function posters (certain educational materials are allowed) and marveled at how polite oncologists were as compared to other specialists he had experienced. “It’s so nice,” he remarked, “There’s no grabbing,” To which a veteran rep standing nearby responded, “That’s because there’s nothing to grab.”

It will take time to adjust, but on the whole, pharma companies and their reps are resolved to the new paradigm, and, for lack of choice, are determined to find their way. Celgene, instead of offering a monogrammed laser pointer as a prize for winning a quiz now donates to charity in your name; Pfizer is now exclusively reliant on the popularity of their perennial offering a CD ROM of ASCO abstracts; and Genentech, the reigning king of gadget-land introduced their cosmic-looking “orb”, a beachball-sized touch-screen device that highlights their technology.

While pharma is readjusting, physicians are, for the most part, relieved. “Several years ago [one company] gave out these horrible bags that people were dragging behind them that we couldn’t stand – they got in everybody’s way,” said Jordan Berlin, Vanderbilt University. Practicality also appealed to Stefan Korec, Alamagordo, New Mexico, “On the one hand it’s great – the toy collectors aren’t there so we have more time to spend in the booth and talk to the reps. On the other hand some of those toys were useful, even instructive. But I agree with the no toys policy… now if that could only lead to a reduction in drug prices!” Korec’s was a common observation; gone were the snaking lines of highly paid professionals waiting for a chance to win a $10 memory stick. Reps were accessible; substantive conversations could be had.

So, there was that. But was it less fun? “My life is pretty fun,” said Halle Moore, Cleveland Clinic, “I don’t need pharmaceutical companies to make my life fun.” And the fun not had in the exhibit hall extended to the lack of receptions, or novel field trips. This was no loss to Adam Brufsky, University of Pittsburgh. “Frankly, I don’t need another trip to SeaWorld,” he said, and in his opinion the restrictive PhRMA guidelines were missing the forest for the trees. “There are a lot of different motivators for people in academic medicine, and money [in cash or prizes] is down the list.” He considers prestige to be the true coin of the realm. “Most of the malfeasance that has occurred in our business has to do more with people fudging data for grants, for promotion.”

Banning pens won’t have an impact on that. “Toys are fun,” Brufsky said, (as he thoughtfully sipped his Genentech-provided smoothie) “but it’s kind of insulting to believe that an oncologist could be swayed one way or the other just because you get a free jump drive that says Novartis on it. Hopefully we’re smarter than that.”

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Finding and Achieving Value in Cancer Care

2009-03-18T10:26:00.000-07:00

The NCCN annual meeting grew in attendance again this year. In these days of slashed budgets it is rare to see growth in travel, and perhaps that speaks to the relevance of the NCCN meeting, both clinically and economically, to today’s oncology environment. Increasingly, NCCN guidelines are playing an important role in the “value” discussion. With the watershed events in ’08, i.e., United Healthcare accepting NCCN guidelines as the basis for coverage decisions and CMS officially recognizing the NCCN guidelines as a mandated reference for coverage decisions, the NCCN is clearly being brought into the managed care/evidence-based medicine spotlight.

At the recently held NCCN meeting, one of the more exciting sessions was the roundtable discussion titled, “Finding and Achieving Value in Cancer Care”. Moderated by Clifford Goodman, PhD, of The Lewin Group, the panel included Dr. Joseph Bailes (ASCO), Dr. Stephen Edge (Roswell Park), Dr. A. Mark Fendrick (Univ of Michigan Comprehensive Cancer Institute), Dr. Scott Gottlieb (American Enterprise Institute), Dr. Robert Mass (Genentech), Dr. Lee Newcomer (United Healthcare), and Lynn Zonakis (Delta Airlines).

Setting the Stage for the Discussion
Lynn Zonakis of Delta Airlines represents approximately 200,000 insurable lives at Delta Airlines. In her analysis 449 of those people drive 77% of the cost of the health plan at Delta. Of the 449 people about 25% of them are cancer patients. This is probably typical of most large companies where a small number of beneficiaries drive health care costs, thus driving the importance of value in health care including cancer care.

Dr. Bailes and Dr. Edge agreed that the rise in the number and cost of single source drugs has brought the value discussion to the forefront in the last 4-5 years. At the same time there has been an awakening in terms of quality in the last 10-15 years. Value is that balance between cost and quality.

How is Value Measured in Terms of Cancer Care?
Dr. Newcomer emphasized that value has two components: 1) an improvement in outcome, and 2) reasonable cost. But what is an affordable/reasonable cost? Cancer care providers, amongst everything else they do, are not in the best position to determine a reasonable cost, so now we’re looking for something that providers can’t demonstrate. That simple fact, the fact that there isn’t sufficient data, is at the root of the problem when trying to identify value in terms of cancer care. The current stimulus package being introduced by President Obama does not contain recognition of cost. This makes it difficult to assess quality since decisions around cost and value should be made as close to the patient and the oncologist (or any physician) as possible. The government can’t do it effectively.

Dr. Fendrick thinks we should bring health back into the health care debate. Right now the debate seems to be centering on money, not quality. Value Based Insurance Design (VBID) accounts for heterogeneity of patients. “A patient in a high-risk group for colon cancer could actually be paid to get screened, while someone in a low-risk group has to pay for their colonoscopy,” he said.

As insurance companies forecast their costs, they are raising their premiums to cover the increased costs. This is forcing some people to leave the insurance company. “The insurance companies have to decide how much they can afford to spend on a given case or they will have to drop coverage of some people. If the trends continue, we’ll see a collapse of the health care system much like we saw mortgages cause a collapse of the economic system,” forecasted Dr. Newcomer.

Dr. Fendrick pointed out that consumers don’t buy products without information on both cost and quality, and yet, “this is not true for the purchase of health care.” He further said that doctor visits are down in the US reflecting sensitivity to cost – in this environment people will stop doing the things that are of high value and the things that are of low value.

Representing a manufacturer of high cost cancer drugs, Dr. Mass reflected that the value discussion does not make him nervous. “We provide products and data so that physicians can make informed decisions, and we set a price based on the value that Genentech perceives those products bring to market”, he said.

All the panelists agreed that the driver for quality in cancer care is improved survival, however, access to the drugs and screening that extend survival cost more money. “Cost is something we should be asking for, but value is something that should be assumed,” said Dr. Edge. “Cost isn’t measurable until we have a system that provides good, consistent, measurable, quality,” he further added.

Other Interesting Contributions Included:

We have a tort system that prevents us from setting up rigid access guidelines. This is nice to talk about but hard to operationalize. (Dr. Bailes)
Clinical outcomes are objective, and value is subjective. (Dr. Fendrick)
In cancer care we need evidence. For example, the use of Herceptin in adjuvant breast cancer should require a co-pay of $0 from the patient. But in the metastatic patient, where there isn’t as much efficacy evidence, the patients should pay a portion for their Herceptin therapy, and so on. But this creates a logistical problem for the insurer. Imagine trying to apply different co-pays to all the different patients in a plan. (Dr. Newcomer)
It is unlikely that we will have a system that puts a value on one year of life the way it is done in the UK, and instead comparative effectiveness will likely extract price concessions. (Dr. Gottlieb)
We have a limited pot of money making small employers want to drop insurance for their employees, and many more want to. (Zonakis)

Perspective
It isn’t often you can witness a group representing a broad group of stakeholders in the room together. The only group missing from the discussion was CMS, although I’m not sure they can say anything at this time anyway. The theme of value, cost vs. quality, is reaching into all aspects of cancer care. From insurance carriers to patients to politicians to providers, all stakeholders are impacted by this discussion as we try and configure a health care system that allows access to quality cancer care at a reasonable cost.

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What's on Radar These Days?

2009-03-05T09:46:00.000-08:00

It’s notable that in President Obama’s recent, first speech before Congress, the only disease mentioned in addressing the country’s urgent need for health care reform was cancer. Obama pledged “to seek a cure for cancer in our time,” a tall order that has so far eluded researchers.

Each cancer drug approval and every trial represents yet another step towards achieving that elusive goal. Yet we were reminded again of the risks associated with cancer drug development last week with the negative outcome of the Phase 3 study evaluating elesclomol [Synta, GSK] in melanoma. With that in mind, we wanted to pique your interest in looking at OBR’s RADAR, just updated, to see what’s on the horizon in 1H09 for oncology drugs in the way of pending FDA decisions and anticipated key clinical trial data:

Pivotal Phase 3 results due:

Mid-April 2009: Avastin® [Genentech/Roche] adjuvant colon cancer data from the NSABP C-08 trial
April 2009: Provenge® [Dendreon] advanced prostate cancer data from the IMPACT trial
June 2009: picoplatin [Poniard] small cell lung cancer data from the SPEAR trial

Upcoming PDUFA action dates:

March 9, 2009: Afinitor® [Novartis] for advanced kidney cancer
May 24, 2009: Clolar® [Genzyme] for adult acute myeloid leukemia (AML)
July 2, 2009: Zevalin® [Spectrum Pharmaceuticals] as first-line consolidation therapy in B-cell follicular non-Hodgkin's lymphoma (NHL)

OBR Radar was developed to keep our reading audience ahead of market moving events in oncology. For more information and the latest updates, go to http://www.oncbiz.com/radar.php or just click on the RADAR icon in any edition of OBR daily.

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Payor Perspectives on Oncology Reimbursement Reform

2008-11-24T09:40:00.000-08:00

Recently I attended the 2nd annual Cancer Center Business Summit held in Chicago, October 20 and 21. One of the sessions titled “Payor Perspectives on Oncology Reimbursement Reform” was of particular interest amongst 2 days of sessions and workshops. Below you’ll see a summary of this session.

The session was moderated by Peter Eisenberg, MD, of California Cancer Care, the panel included Michael Koloziej, MD, Medical Director, Medical Oncology Services, US Oncology, Allen Lichter, MD, CEO, ASCO, Lee Newcomer, MD, Senior Vice President, Oncology, United Healthcare, and William Rogers, MD, Medical Officer, Office of the Administrator, Director Physicians Regulatory Issues Team, Centers for Medicare and Medicaid Services.

They all did a great job of providing differing perspectives in the payer/provider realm and a lively discussion ensued. Following are some of the ideas that were expressed by the opinion leaders about this topic.

US Oncology’s Innovent Oncology
Opening the discussion, Dr Koloziej explained how US Oncology’s new model—Innovent Oncology—is proposed to provide resources that can enable more collaboration and communication between providers and payers which can lead to agreed upon treatment algorithms that maintain quality while controlling the cost of care. Dr. Koloziej called Innovent a “matchmaker” and said that the idea behind Innovent is to provide oncologists with pathways, disease management, and advanced care planning support tools and services.

Dr. Lichter: Shifting the Cost of Therapy
Dr. Lichter spoke about an interesting new insurance model that the University of Michigan is experimenting with. The hypothesis behind the experiment is that if you shift the cost of therapy to patients—meaning you force them to take on greater financial burden associated with their therapy in the form of co-pays—you will decrease compliance. In the experiment, they are cutting co-pays to $0 so that the drugs are free to patients, and then compliance is being monitored. The study is underway and results are pending.

Viewpoint from CMS
CMS is the nation’s largest insurer and, Dr. Rogers reminded the audience, it is the only insurance company that is managed by Congress. This puts CMS in a very unique situation and in some cases limits what CMS is allowed to do. For example, some believe that co-pays for cancer therapies could be adjusted according to outcome i.e., the cost of cancer care could be shifted to patients by creating a tiered co-pay structure for cancer care. In this scenario, a patient may pay a 2% co-pay for Avastin-based therapy in an approved indication with a predictable outcome, but using Avastin-based therapy with an unpredictable outcome in an unapproved cancer indication, that same patient would have to pay a 40% co-pay. However, what many don’t realize is that this scenario is not possible at CMS unless it is mandated by Congress. By statute, CMS has to require a 20% co-pay from everyone, regardless of their condition.

Dr. Rogers also reviewed some of the other thoughts currently going on at CMS:

PQRI was intended to test the ability to collect quality data through the claim form. At this point it is clear that oncology offices have not been compensated at a fair rate for their time in compiling that data and there is basic recognition within CMS that PQRI has room for improvement.
Conceptually through MIPPA (Medicare Improvements for Patients and Providers Act) CMS should be able to collect data and create a report card which compares the way one MD treats a condition, such as congestive heart failure, with the way peers are treating that same condition.
Recovery Audit Contractors (RACs) are here and Congress is under the impression that RACs are a low cost way to recover a lot of money from fraud and abuse. But you don't have to worry too much about them visiting your office in the near future, because their incentive is to go after the big bucks, which is in the Part A hospital setting. That is where their efforts are likely to be focused.
Regarding comparative effectiveness, Dr. Rogers pointed out that Medicare doesn’t have the authority or expertise to implement anything based on differential payments for comparative effectiveness. But, at any time, Congress can pass a law giving them authority. Right now the only tool they have is National Coverage Decisions, which is a blunt tool for implementing the results of data-driven studies. As Dr. Rogers sees it, if given the authority by Congress, CMS could implement such a program, which could improve outcomes and help oncologists. Dr. Rogers mentioned that NICE, the National Institute of Chemical Excellence, the UK authoritative healthcare body, has a cap of £36,000/patient/year for any given condition, and that is it. This will not work in the US, so he is not sure in what direction the model is going.

United Healthcare’s Lee Newcomer, MD
Dr. Newcomer, probably in an intentional effort to elicit an audience response, brought up a new initiative that United Healthcare is piloting called “episode-based payments”. To buy into episode-based payments, one has to believe that the buy and bill system, as it stands today, is fundamentally flawed in that it does not align incentives properly.

United is piloting episode-based payments in 3 or 4 practices in the country where patients are divided into similar groups (such as ER+ metastatic breast cancer, or HER2+ metastatic breast cancer). Those practices are then given a payment up front on day 1 of treatment for those patient types. United is calculating the profit normally acquired by the practice for a 6-month course of therapy in that patient type, and then sends the practice a check up front. Drugs are otherwise paid on a cost pass-through basis with no mark-up. If the patient and doctor decide not to continue the course of therapy throughout the 6-month time period, the check stays with the practice.

Dr. Newcomer described the episode-based payment model as a revenue neutral approach to the practice, but aligns the incentive into the right place. One of the interesting aspects of episode-based payment is that it takes away the incentive for one more course of therapy and therefore improves end of life therapy. There is a lot of data showing that patients are receiving treatments within the final weeks of life, and this could fix that problem.

Dr. Newcomer noted that this model is a pilot, an intermediate step, and that there are big logistical challenges. As he said, if United takes steps toward aligning the incentives better, and others learn from it, then they have made a beneficial difference in the way healthcare is delivered in the US. If the pilot doesn’t work, then other carriers will, at the least, know what not to do.

The Cancer Center Business Development Group (CCBDG) is a business forum that explores cancer care relationships through mergers, and consolidations or affiliations. Their goal is to bring together cancer care providers—who are concerned with the current economics in the oncology practice model—with key thought leaders from the financial and business world.

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Proceedings of the 3rd Annual Onmark Payor/Provider Forum

2008-10-20T09:00:00.000-07:00

As the economic realities of today’s cancer care environment are forcing stakeholders to balance cost with quality care, meetings such as Onmark’s 3rd Annual National Payor/Provider Forum not only stirred emotions, but provoked such questions as: What will the cancer treatment model look like one year from now? Or even three years from now? How large of a role will private insurers and Medicare play in treatment making decisions? Will Medicare and private insurers seek out information from providers before making sweeping decisions?

At Onmark’s recently held meeting, the goal was to provide a national forum where oncology stakeholders could come together and discuss best practices, debate viable solutions, and potentially glimpse into the future model of oncology care in hopes of helping to shape that model and advance patient care.

Enter McKesson Specialty
McKesson acquired Onmark and OTN in October ’07. This gave them a full spectrum oncology business and provided them the opportunity to connect oncology stakeholders with meetings such as this one. The President of McKesson Specialty, Patrick Blake, opened the meeting by stating that all oncology stakeholders are seeking the highest quality of care with the most economically efficient model. But to accomplish such a model will require cooperation, consensus building, and increased levels of transparency between all stakeholders. As Mr. Blake pointed out, no single group working alone is going to crack the code to improve the cost, quality, and outcomes in cancer care.

Several Trends in the Healthcare Delivery Model to Watch Out For
Peter Bach, MD, Associate Attending Physician at Memorial Sloan Kettering, who was the moderator of the meeting, brought forth some provocative thoughts to consider. He claimed that we are at a very exciting and worrisome time in our healthcare system. He feels that our current system is poorly designed for efficient use of resources to deliver high quality care for the optimization of patient outcomes; and asked: How do we best ensure that whatever system we evolve toward is fiscally stable or sustainable while at the same time focused on patient care?

According to Dr. Bach, oncology in particular is in the spotlight, as it should be, regarding the high cost of cancer drugs and interventions. Anecdotal projections based on Medicare reimbursement rates show that there is an approximately 8% compounded growth rate in the price of oncology drugs (adjusted for inflation) which creates intense cost pressure and very poor prospects of maintaining the fiscal picture in oncology without some sort of change.

He continued to say that as we look forward into our healthcare struggle where the trends include inconsistent quality of care, rising incidence of cancer, a shortfall of workforce, a constrained payment environment, and rising cost of drugs, there are several things to worry about or look forward to (depending on whether you’re an optimist or pessimist):

Rising drug costs will increasingly be subjected to some sort of price manipulation, either market oriented or payer oriented. For example, the buy and bill method may become the target of price manipulation by payers.
The CAP program, although not successful, could become a model for the future. The problems with the program are starting to be identified and payers understand that having an intermediary and competitive bidding could create significant cost savings.
Coverage restrictions for the private sector and the government are going to become more prevalent. Statutory limits in place right now are being re-evaluated. The ESA changes at Medicare and some of the private payers are a harbinger of things to come. These restrictions will also be very tough battles for all stakeholders.
Episode-based payment, case-rate payment, prospective payment, whatever you want to call it, is being actively investigated and we should be ready for it. There is every expectation that cancer care doctors will get paid for a bundle of services and the discretion around those services will be on the doctor and the patient. Hopefully, the reimbursement level will be adequate to support evidence-based medicine and high quality care for all patients. If we think about oncology practice finances, the use of prospective payments will fundamentally shift the alignment of incentives and take the ability to garner profits based on the spread between purchase price and reimbursement amount of oncology drugs off the table as an issue.
There are a lot of people interested to see an approval pathway for generic biologics, and we can expect to see activity directed toward finding a way to do this.
Safety concerns will become greater for oncology, particularly in the adjuvant setting. New post market surveillance legislation is likely to bring to the forefront a greater incidence of safety concerns with oncology therapeutics.

Doing Well By Doing Good: Maintaining Quality While Controlling Costs
As most know, Dr. Lee Newcomer is the Senior Vice President for Oncology at United Healthcare. He presented a provocative question: Why does it matter that we maintain quality but manage costs? The answer he provided is: because for many Americans healthcare premiums outstrip mortgage payments. In the future, maybe in the next 5 years, the healthcare bubble is likely to burst much like the one we’re seeing on Wall Street today. The data doesn’t support the concept that if you want to increase quality all you have to do is throw more money at it.

So what do we have to do? The first thing is probably get consistent in our healthcare delivery because it will ultimately lead to improvements. He gave several examples of large variations in cancer care treatment decisions at UHC. The underlying theory is that if UHC is consistent in its treatment of patients:

error rates will fall
the group can improve systematically
they can develop evidence-based best practice guidelines
apply the guidelines into clinical practice
then measure, learn from, and eliminate variation

Improvement requires measurement, and measurement can’t happen without consistency. Dr. Newcomer shared a great quote attributed to Brent C. James, MD, Intermountain Healthcare when he said, “It is more important that you do it the same than that you do it right”.

Initially, the idea is that groups with a consistent approach to healthcare delivery will get the database of information back which could be used as a basis for discussion. The data will not be used to generate a bonus or a penalty, but down the road this data could somehow be tied to financial performance.

At UHC, the next steps to move toward consistent care, and therefore maintain quality while controlling costs, are likely to include KRAS testing for metastatic colon cancer, starting dose rules for erythropoietin, and potentially, someday, implement episode payments.

Concluding
Dr. Bach, being at Memorial Sloan Kettering and having spent a considerable amount of time at CMS, and Dr. Newcomer, being an oncologist and medical director at one of the largest private insurers of cancer patients, seem to be at the forefront of the current thinking regarding a new cancer treatment model. Stay tuned as we follow their viewpoints and watch for changes in the evolving cancer care delivery model. Thank you to Onmark and McKesson Specialty for organizing and hosting this valuable meeting. The next Onmark Payor Provider Forum is scheduled for October ’09.

For more on this topic, we recently published an extensive article regarding these types of questions in the September issue of OBR titled “Tearing Down Walls”: Download a full-length PDF of this article

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Tracking And Interpreting OBR Data in August 08

2008-09-04T15:51:00.000-07:00

August is a sleepy time of the year when everybody is focused on the sand between their toes and important decisions like SPF 30 or SPF 50, right? Wrong. It turns out August ’08 was yet another active month for oncology news and events. In case you missed any of these, I decided I’d recap some of the more meaningful activities we saw here at OBR and share them with you. I’ve broken them into three categories:

OBR Daily
The following table lists, in order, the top 5 widest read news articles on OBR daily for the month of August.

It appears that the debate over CME is top of mind for our oncology readership, and of course new product approvals are always of interest. All these new stories are available on the OBR daily news archives on our website if you want to look back.

Tumor Ticker
What makes for another very interesting story appears in Tumor Ticker. In case you haven’t noticed, we calculate the top 5 winners/losers based on % gain/loss on tumor ticker streaming stock quotes every day. What happened in August? The table below shows the top 5 winners/losers for the entire month.

I know what you’re wondering, where are the Genentech and ImClone deals and ensuing share price appreciations? Those announcements were in July. But isn’t it interesting that the third most read story in OBR daily is about a promising new lymphoma drug that just happens to be owned and developed by Micromet, the number 1 most appreciated stock in Tumor Ticker for the month. Makes you wonder, doesn’t it? On the bottom of the ladder we saw Avalon announce that they need to secure financing, and of course Cell Genesys announced that there were a higher number of deaths in the experimental GVAX arm as compared with the control arm, sending that stock plummeting.
You can view the entire Tumor Ticker here

OBR Radar
OBR Radar is our forward looking product anticipating important upcoming oncology events. So while we can look back at August and perhaps draw some conclusions, you may also want to see that there are a few important events coming up. Things to keep an eye on:

You can see more upcoming events listed in the OBR Radar

In Summary
We’ll keep doing these summaries, monthly or even weekly. Which would you like? Our goal is to provide our readers with an opportunity to catch up, remind you what the most recent big stories were, and keep you from being surprised by an upcoming announcement. Let me know if you like it.

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Four Years After Thinking About Compendia, NCCN Drugs & Biologics Compendium Recognized By CMS

2008-06-09T11:10:00.000-07:00

Before his time leading the National Comprehensive Cancer Network (NCCN), Bill McGivney spent six years with Aetna as head of national coverage policy and its national P&T committee. “I understood the payer perspective,” McGivney said, reflecting today on one of the intangibles that helped NCCN earn a major policy and organizational success last week.

On June 5, CMS recognized the NCCN Drugs & Biologics Compendium™ as a mandated reference for the establishment of coverage policy and coverage decisions regarding the use of drugs and biologics in cancer care.

CMS decisions are expected shortly on whether the agency will also add three other compendia: Thomson’s DrugDex and DrugPoints, and Clinical Pharmacology’s Gold Standard.

For oncologists, the decision potentially means an ease on practice administrative demands and a boost to clinical decision making at the point of care. As of June 5, physicians can begin to reference the NCCN approved compendium for Medicare Part B reimbursement.

Medicare local contractors, who process and pay Medicare claims and approve coverage for drugs under Part B, use compendia as one of several tools to determine whether an anti-cancer drug should be covered under Medicare Part B.

Until this decision, oncology and hematology practices complained that NCCN was not among the approved compendia, and yet for many it was the most current. In research published in OBR earlier this year (http://www.oncbiz.com/documents/OBR_0108_Compendia.pdf), 81% of oncology practices surveyed said that CMS and commercial payers ought to adopt NCCN as a gold standard.

“This has been a long road when we started four years ago thinking about compendia. We had a good collaboration with CMS all along,” said McGivney, PhD, NCCN’s chief executive officer. “We listened to them and knew there would be twists and turns, but we focused on the goal and established improvements to our electronic system so anyone could utilize it.”

For McGivney, you can tell the announcement serves as a personal victory but one that means more for the cancer care system. “This greatly benefits patients … our guidelines are the standards for clinical oncology and integrated with expert medical judgment.”

If you're in industry or a provider or at some other corner of the cancer continuum, one policy lesson clearly emerged from this process: transparency wins. Says McGivney: “CMS was very interested in the openness of our process and that we made [our compendia] free, that our doctors do this free of charge, most for about 10,000 hours a year.”

Bottom of the Ninth, and Now Two Away: Is the Game Over for Personalized Immunotherapy?

2008-05-30T17:26:00.000-07:00

San Diego – Specifid, a therapeutic agent once poised to be not only be first in class, but first in concept, has failed to meet its primary endpoint in a phase III registration trial of patients with non-Hodgkin’s lymphoma (NHL). This result, announced May 27th has prompted Specifid’s manufacturer, Favrille, to discontinue any further development of the compound. “With respect to getting any useful positive information that would lead to approval out of this data set,” said John Longenecker, PhD, President and CEO of Favrille, “that’s not going to happen.”

Specifid is the second such personalized immunotherapy to be abandoned in the last six months, the other being Genitope’s product, MyVax, which was withdrawn from development last December. Despite that cautionary event, Longenecker had remained confident in his molecule’s ability to perform. “Unlike MyVax, which was expressed in mammalian cells, our patient-specific idiotype (antigen) protein was made in a baculovirus/insect-cell expression system. That meant the protein was only glycosylated with mannose sugars, which is far more antigenic than that produced by mammalian cells.” Specifid was also produced as a nano-particulate formulation, which theoretically allows a patient’s immune system to more easily “see” the antigen. But these distinctions, impressive on the benchtop, bore no statistical significance in the clinic.

In Specifid’s pivotal trial, patients with follicular B-cell non-Hodgkin’s lymphoma were pretreated with rituximab – the current gold standard in this setting – and then randomized in a 1:1 fashion to either Specifid plus GM-CSF (granulocyte-macrophage colony-stimulating factor) or GM-CSF plus placebo (N=349). Following treatment induction, patients with stable disease or disease remission at six months were continued on a maintenance program consisting of the assigned randomized treatment every two months for one year, and then every three months thereafter in the absence of disease progression. The study endpoint was a comparison of times to disease progression for the two treatment arms. Results showed that, even in a mixed cohort of treatment naïve, treatment refractory, and relapsed patients, no clinical outcome was superior for active treatment. “We did a very thorough analysis,” says Longenecker, “All the sub group analysis… we looked at progression as assessed by a number of criteria, but all of the data is consistent and shows no difference between the placebo and treatment arms.”

This newest failure of a personalized therapy is perhaps more striking than the demise of dissimilar novel compounds because an immunotherapy should work in much the same way as a vaccine – of which we have many. As long as the antigen is well defined and consistent, as would be expected in a clonal population of tumor cells, inducing an immune response should be relatively straightforward. So… why isn’t it working? “The short answer is, we don’t know,” admitted Longenecker. He has a suspicion or two, one being the timing of the immunotherapeutic dose after treatment with rituximab – an agent which depletes the B-cell population required for an immune response. Favrille’s strategy was to dose with the active immunotherapy at a time of minimal tumor burden, which would be within a few months of rituximab administration, yet prior to full B-cell recovery. “There’s a theory that you need B-cells to recover from Rituxan in order to get a maximum immune response… but that remains an area of speculation.”

Longenecker is not the only one giving the matter some thought. Investigators at BioVest, makers of the last remaining personalized immunotherapy in development for NHL, BioVaxID, have their own ideas. “We believe the only way to get an effective reaction out of the immune system is to use true copies of the tumor markers,” said Steve Arikian, M.D. Chairman and CEO of BioVest. And this has to be done through the use of hybridoma technology. “You get high fidelity copies of the tumor idiotype (antigen) which is how we got such strong immune response data from our phase II trial.” Arikian wonders if Favrille had the right idea, but the wrong method – their recombinant idiotype product was simply too imprecise to efficiently mimic the endogenous target.
BioVest’s own trial, which began enrollment in 2000, differs for the Favrille investigation in that it used an adriamycin-based chemotherapy to induce the initial disease remission, and the active immunotherapy was only administered after a six month “holiday” in order to allow time for the patient’s immune system to recover. Arikian believes this difference will be critical to producing a significant outcome in the active treatment arm.

The unblinding of BioVest’s trial is slated for late June, yet, even a positive result may not matter. As Favrille’s CEO points out, “We live in a Rituxan dominated world.” The two trials combining immunotherapy with chemotherapy-induced remission were extremely difficult to enroll, and essentially, behind the times. “Genitope took 4 years, and BioVest took 8 years – both programs excluded Rituxan. That will complicate whether [a positive outcome] will find a place in the market.” Rituximab rules. The order of the day is not to rescue chemotherapy, but to find a way to use your drug in a rituximab combination.

For now, Longenecker thinks that anyone looking to enter the patient-specific immunotherapeutic field should first return to the drawing board. Is B-cell recovery necessary? Are T-cells down-regulating a therapeutic immune response? “Our trial has demonstrated that it is possible to develop an immune response against your own idiotype proteins. The question is, how do you take that observation and convert it into a clinically useful approach?”

On-Conversation with John McCamant

2008-05-20T10:18:00.000-07:00

John McCamant is the editor of the leading investment newsletter Medical Technology Stock Letter. He has established an extensive network of contacts in the investment banking and venture capital communities. His expertise in the field of biotechnology investments is a subject of media interest, and as a result, he is frequently consulted and quoted by The Washington Post, Business Week, Reuter’s, and Worth. In addition, John has been featured on CNN and CNBC. He gave us his thoughts on last week’s release of the ASCO abstracts, and even a little free advice.

OBR: We’ve all heard that this is the first time that ASCO is releasing the abstract data to everyone at the same time. Did you and your team have to pull an all-nighter?

JM: Yes and no. We did spend a lot of time digging through abstracts. However, because we are based on the West coast, we had access at 6 p.m. our time, which meant we could both get a lot of work done and still manage to get some sleep. To be perfectly honest, we are quite pleased that ASCO has “seen the light” and changed their policy to reflect the real world of clinical trial results disclosure. By real world, what we mean is that if nothing else, it is now being acknowledged that ASCO data does affect/move stock prices. In the past, this policy has disproportionately affected the smaller biotechs. The bottom line is that ASCO has a responsibility to disseminate information evenly and fairly, and the changes they made to their policy for this year represents a solid step in that direction.

The new policy makes very good sense, but does beg one question. What was ASCO waiting for? In the past, the abstract books were mailed ahead of the actual conference to ASCO members only. As a result, the accompanying clinical trial data was only available to a select few and individual stocks often began to move. The majority of investors were in the dark as to how this was happening as the information was not yet public. With the new policy, everyone has access to the available information at the same time. All one has to do is look up the abstract on the Web.

OBR: The big news in the late-breakers and plenary session presentations is embargoed until the meeting. Did this year’s batch of abstract data warrant all this attention?

JM: As mentioned above, it was their outdated policy and the fact that no other medical conferences had the same policy that has attracted so much attention. As for the abstracts themselves, they appear to not have had a major effect on stock prices this year. I would guess that it has more to do with there not being a lot of critical or surprising data, and less to do with the playing field finally being leveled. Plenary sessions are chosen for their “juice appeal,” so they should represent some of the most influential/stock moving data. In addition, late breakers will have updated/new information in them that may also be influential. Furthermore, the abstract data is generally from December/January time frame, meaning that many will have updated data at ASCO that is fresh.

OBR: Let’s dig into it, what is your take on some of the highlighted research data released last week. What companies are you focusing on for the upcoming annual ASCO meeting?

JM: We believe that Wall Street usually does a good job covering the bigger names in biotech. The following two companies are not as well covered by Wall Street and represent two of the more attractive investment opportunities within the oncology investment space:

Incyte (abstract #7004) showed data from a Phase 1/2 trial testing INCB18424 in 32 myelofibrosis (MF) patients and patients with post polycythemia veraessential thrombocytopenia myelofibrosis (Post-PV/ET MF) in which all patients were given 25 mg BID. The 25-mg dose was the starting and maximum tolerated dose (MTD)—an expanded cohort of 21 patients has also been enrolled at the MTD. All of these patients have been on drug for at least one month. Two patients had grade 4 thrombocytopenia at 50 mg, which defined the dose-limiting toxicity. This is a normal response to a high dose, and not unlike that seen with other drugs that treat blood cancers. No other significant drug-related toxicities were observed. The key result was a significant and dramatic reduction in splenomegaly, with reductions of 53% at one month (in 24 patients), and 76% at three months (in 7 patients). In addition to improved constitutional symptoms, drug-related effects reduced the dependence on transfusions and resulted in a decrease of proinflammatory cytokines—the so called “cytokine storm” that lies at the core of MF patients’ symptoms. Investigators concluded: “Treatment with [INCB18424] results in unprecedented clinical activity in MF and post-PV/ET MF without significant toxicity.”

Final thoughts: The updated presentation at ASCO will have much more data, maybe as much as four additional months worth, which we believe will result in a strong ASCO for Incyte. The data should serve to stimulate Wall Street’s interest as the company positions INCB18424 for the upcoming pivotal trials.

GenVec’s data from a Phase 1 dose escalation study of TNFerade (abstract #6067) in conjunction with chemoradiotherapy in patients with recurrent head and neck cancer (HNC) are going to be presented at this year’s ASCO meeting. In this trial, eligible patients have locoregionally recurrent, previously-radiated HNC and performance status 0-2. Patients are receiving 5 days of daily radiation along with continuous infusion of the chemotherapy agents fluorouracil (once daily for 5 days) and hydroxyurea (twice daily). (This combination chemo regimen is referred to as FHX.) Additionally, TNFerade is being administered to patients in escalating doses ranging from 4x109 to 4x1011 PU on day 2 of each cycle by direct intramural injection. Three to six patients are entered on each cohort, and treatment cycles are repeated every other week. At the time of the abstract submission, 10 patients (total) had been entered on three dose levels. Dose level 1 was expanded to 6 patients following observation of possibly related dose-limiting toxicity in one of the patients. Subsequent to this, no dose-limiting toxicity was observed, and patients are currently entered on dose level 3. Overall, the toxicities which have been observed in the trial, such as grade 3 mucositis and dermatitis, are not suggestive of an interaction between TNFerade and FHX. Once the MTD has been defined, the dose of radiation will be escalated.

The bottom line at the time of the abstract submission is that it appears as if TNFerade can be added to concomitant FHX-based chemoradiotherapy in the HNC patient population. This is important, because new treatment options are certainly needed. The simple fact is that the prognosis for patients with locoregionally recurrent HNC remains poor, and a high percentage of these patients that are re-irradiated with concomitant chemotherapy end up experiencing disease recurrence. Of course, TNFerade will not only have to show that it can merely be added to chemoradiotherapy. It will have to show that it offers the potential for improved treatment outcomes. To this end, in addition to updated toxicity data from this trial, early efficacy data from the trial are also going to be presented at ASCO.

Final thoughts: We believe that additional efficacy data in the HNC treatment setting will provide further validation of the already impressive results that TNFerade has produced in the pancreatic cancer treatment setting (its lead indication), and could provide a catalyst for GenVec’s stock.

IMS Forecasts 12%-15% Growth for Global Cancer Markets Over the Next Several Years

2008-05-15T11:34:00.000-07:00

Today, IMS Health released their predictions for the global oncology industry. According to the forecast, global sales of cancer drugs will grow 12%-15% and reach $75 to $80 billion by 2012, nearly doubling the forecasted growth rate of the global pharmaceutical market (6.4% in 2007). Twelve to fifteen percent growth for the next several years doesn’t jive with the constraints in oncology markets that our industry feels today. There has been remarkable expansion over the last few years (the AWP years?), and in spite of the predicted 12%-15% growth, this industry feels like it is contracting not expanding.

Go west, east, or south of the US. According to IMS, this growth will be driven by the increasing number of cancer patients receiving chemotherapy in Europe, Japan, and North America. Also evidenced is the fact that more patients in emerging markets such as China, Brazil, South Korea, Mexico, India, Turkey, and Russia are getting access to up-to-date targeted therapies. Maybe this explains my instincts. The constraints I feel are real, and the growth that IMS is referring to is coming from ex-US markets.

IMS identifies the following as key dynamics that are influencing the double-digit growth of cancer products through 2012:

• Financial constraints of payers in major markets are leading to increased rigor for selecting targeted therapies – I see, major markets must mean the US. Now this is making sense.
• Improved screening, diagnosis, and access to modern medicines in developing countries – that’s real progress, access being the key in my opinion. Keep it coming.
• New products and combination therapies – of course there is still the tremendous amount of investment and effort to develop new products, some of which may actually make it to market.
• Growth rates for the top markets decrease – finally somebody said it. I knew it didn’t feel like a 12% growth rate here in the US.

Over the next five years, IMS is predicting in its annual forecast that growth will level out due to
• Tapering of current blockbusters - read: Avastin, Herceptin, Gleevec, etc.
• Fewer newer blockbuster medicines - predictive biomarkers may have something to do with this.
• Loss of exclusivity of four oncology products that have annual sales of over $1 billion - inevitable, but let’s get the lawyers on the phone.

IMS also predicts that future growth will be bolstered by the introduction of 25 to 30 new chemical entities between 2008 and 2012. These new entities will help sustain the trend of the expanding patient population being treated with targeted therapies. While many of these new therapies will target the most prevalent tumor types, namely breast and NSCLC, several will focus on late-stage prostate and pancreatic cancers as well as melanoma.

A strong finish. Twenty-five new chemical entities over a five-year period would be excellent progress. So far through ’08 we’ve had two new oncology approvals: Levoleucovorin (not sure if this counts) and Treanda. We’ve got a lot of work to do to get those 25 NCEs on the market, and contributing to predicted growth, by 2012.

Reports like this provoke industry dialogue both pessimistic and optimistic. What does this report invoke in you? In spite of feelings of contraction, the IMS report indicates it is a healthy industry, and the incremental gains found at each ASCO meeting are meaningful for patients, providers, payers, and industry.

Foregoing ASP: Small practice oncologists enroll in CAP

2008-05-12T09:25:00.000-07:00

Signifying a change from 2007 enrollment trends, small practice oncology groups are enrolling directly in the Medicare Part B competitive acquisition program (CAP), BioScrip and several practices shared with OBR.

In early 2007, the Medicare Part B program’s vendor, BioScrip, reported that oncology scripts were written under the program, but very few oncology practices had signed up. “We had almost 300 internal medicine specialists enrolled in 2006,” said Russell Corvese, a BioScrip administrator. “Many had an oncologist in their practice writing the chemotherapy script.”

In 2008, however, oncologists—including several in the New York City area—enrolled during Medicare’s latest sign-up period, January 1 to February 15, according to BioScrip. This means that some oncologists are choosing to forego buying and billing drugs under the average sales price system (ASP) for their Medicare population and, for the moment, are sending a significant portion of their business to BioScrip.

Across specialties, there are approximately 3000 total physicians enrolled in the CAP. OBR will have an exclusive oncology enrollee breakdown, interviews, and analysis in an upcoming issue.

Comparative Effectiveness - What's in a Word?

2008-03-11T10:44:00.000-07:00

I attended the “Comparative Effectiveness” themed roundtable at the annual NCCN meeting last week. I’m still not sure what comparative effectiveness means, or what The Hill crowd is planning with it, but I know there are a lot of people who want to discuss it and seem very concerned about it. Someday I hope to know how the Comparative Effectiveness Institute is going to impact on cancer care giving, but until then I’ll keep attending meetings and picking up tidbits pointing me toward the story. When I figure it out we’ll do an article. Sarcasm aside, if this roundtable was about Comparative Effectiveness, I want more. For oncology wonks, this was a great hour spent contemplating the future of the U.S. healthcare system and in particular the future of the oncology industry.

Perhaps there is an underlying problem fundamental to the term Comparative Effectiveness because we don’t even know what Effectiveness truly means. The roundtable began with an attempt at defining Effectiveness as it applies to oncology, and right away we were faced with the problem of Progression Free Survival (PFS). As Dr. Saltz of MSKCC stated very well, Progression Free Survival implies hope because when you throw that word Survival around, you automatically create hope for patients. Does positive PFS correlate to positive Overall Survival? Does a positive PFS deserve to provide hope to patients? Don’t forget that PFS is defined as the period of time patients lived without the cancer getting worse. What does that have to do with survival? And hope?

As you hear more about Comparative Effectiveness, think first about what Effectiveness is. By just offering up one simple word– survival – a can of worms is immediately opened. Optimists can argue that the cancer industry has made incremental but meaningful gains extending the lives of cancer patients, however, cynics can argue that the progress being made isn’t enough and that it is adding too little time to patients’ lives at a very high cost to the healthcare system. If we want to discuss Effectiveness in oncology, we need to be careful with our words, and be prepared to go down a path with wildly differing opinions on what the Effectiveness bar should be.

In a few weeks, NCCN and OBR will be webcasting the full roundtable discussion for those oncology wonks out there who are interested. I think oncologists and industry alike will find it an entertaining, provocative, and worthwhile hour. Stay tuned.

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New Head-To-Head Study Hopes to Establish a New Model for Global Clinical Trials in Treating Women with Early-Stage Breast Cancer

2008-03-04T22:08:00.000-08:00

In case you missed it last week, the NIH recently announced that a large-scale, randomized, Phase 3, multi-national study will compare Herceptin® [trastuzumab; Genentech Inc.] head-to-head with Tykerb® [lapatinib; GlaxoSmithKline] in women with early-stage, HER2-positive tumors. The ambitious Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Study (ALTTO) will enroll 8,000 patients in 50 countries across 6 continents with GSK supplying the study drug and providing additional financial support.

The 52-week trial has two different designs depending on whether patients are in stage I or stage II and if they have already been treated with chemotherapy. The 4 treatment arms will consist of either trastuzumab or lapatinib alone, or trastuzumab followed by lapatinib, or the two agents in combination. Did somebody say 8,000 patients in 52 weeks? Congratulations on global cooperation in cancer clinical trials which may mean we could get large randomized study results faster.

The goal of this study is to standardize treatment in early stage breast cancer patients. But unsaid in the media to date, is that this study could leave only one exciting targeted breast cancer drug standing after it is all over. I’m sure GSK/Tykerb is excited to fund this study because they have everything to gain and very little to lose. Of course Genentech/Herceptin has everything to lose. But what are the chances that one drug will prove superior to the other, especially compared to the combination? Very low I’d say. Likely outcome is the two drugs will be used in sequence or combination. Oncologist Dr. Edith Perez of the Mayo Clinic in Jacksonville, Fla. and one of the study’s two lead investigators has already said that the trial will probably show that both drugs, working in concert, are more powerful than either acting on their own. So in that scenario Tykerb will be added and will gain some market share without hurting Herceptin. Everybody’s happy, except insurers.

Whatever the outcome, the point is we’ll have an outcome sooner than usual. That’s something to talk about.

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This Week, Perhaps More Than Any Other Single Week, Highlights the Pitfalls in Cancer Drug Development

2008-02-21T10:47:00.000-08:00

Over the last couple of days we've heard a lot about the failure of Nexavar in NSCLC. We’ve heard that as Nexavar’s potential in NSCLC diminishes, Avastin establishes itself as an even more important product for NSCLC patients. At the same time we’re hearing a lot about the looming FDA decision on Avastin in metastatic breast cancer. Maybe it’s too much of a stretch, but I see some sort of connection here.

Nexavar and Avastin are not that dissimilar in terms of mechanism of action. Nexavar is a targeted therapy with two indications that couldn’t meet the overall survival endpoint in NSCLC, and Avastin is a blockbuster targeted therapy with multiple indications that didn’t meet the overall survival endpoint in metastatic breast cancer in their registration study. Maybe the connection is in the study design. So why did Bayer/Onyx include squamous cell patients in their NSCLC study? The Genentech people decided not to include them in the NSCLC registration study for Avastin. If the study was positive Bayer/Onyx would have a population of patients that Avastin doesn’t have, but perhaps that design flaw is responsible for the negative outcome of the study (they say publicly that the squamous cell sub-group had a higher death rate). It doesn’t really matter now except as a learning point for people that design NSCLC clinical trials.

The point is that the roller coaster of cancer drug development couldn’t be in a stranger place today with one targeted therapy failing its registration study and the other a couple of days away from a possible monumental regulatory decision. At the minimum, we will all learn a lot this week about study design, FDA trends, and investment opportunities.

If the FDA decision regarding Avastin for breast cancer is negative, oncologists will have lost access to a great targeted therapy and who knows what will happen with insurers and the 25% market share Avastin already has in metastatic breast cancer. If the FDA decision for Avastin is positive, consider it an admission from the FDA that progression free survival can hold its own and may be equally important as overall survival. That is a precedent which I’m sure the FDA is struggling with.

Nobody in the media is making any predictions, so I’ll open myself up. My prediction is…the FDA will delay their decision on Avastin for 60 days and will wait for more study results, or just use the time to solidify their position. Do you want to make a prediction?

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Interview with John Docherty, President, Helix BioPharma

2008-02-10T21:27:00.000-08:00

The Canadian biopharmaceutical company Helix BioPharma is focused on the development and commercialization of innovative cancer therapeutics, specifically protein therapeutics for cancer. Founded in 1995 through a series of mergers, Helix BioPharma is publicly listed on the Toronto Stock Exchange as HBP. Based on its proprietary core technologies, Helix’s two key initiatives are Topical Interferon Alpha-2b, a treatment for the prevention of the development of cervical cancer that is caused by the numerous strains of HPV; and L-DOS47, an enzyme that specifically targets the environment surrounding lung adenocarcinoma cells to create an anticancer effect.

Helix’s Biphasix™ technology is specifically designed for moving large molecules across the skin/mucosal tissue. The Topical Interferon Alpha-2b cream is designed to deliver interferon alpha-2b molecules to the basal epidermal layer and help prevent HPV infections from potentially leading to cervical cancer.

OBR: Why HPV?
JD: HPV affects 20 million people in the U.S. alone. Once a woman contracts HPV she can develop potentially pre-cancerous lesions of the cervix that may or may not progress to cervical cancer. These lesions are basically abnormal cervical tissue that are dysplastic in nature and, if not resolved, can progress to cervical cancer. The lesions themselves are occurring at a rate of one million abnormal pap smears per year in the U.S. with similar numbers in Europe. Currently, there is no pharmaceutical therapy for these patients and when you look at the numbers involved, we think there is a significant unmet medical need here.

OBR: Right now, what happens when an abnormal pap smear occurs?
JD: There’s a mandate that doctors have to follow in the U.S. and Canada before prescribing a treatment. The only currently available treatments have to be administered in a hospital-type setting because they are surgical or interventional in nature. In mild cases, doctors can use laser surgery or use cryotherapy (freezing) to remove the lesions. In more advanced cases, a LEEP excision is usually performed or a conization which is the removal of abnormal tissue from the cervix. However, in all of these procedures, a battery of side effects can occur that doctors and patients would like to avoid. Side effects can be abnormal discharges, infertility or even pre-mature labor. In lieu of these types of procedures, we hope to provide doctors and patients with a pharmaceutical treatment option.

OBR: Have you completed any clinical studies with Topical Interferon Alpha-2b?
JD: In 2007, we completed a small Phase 2 study in women with HPV-induced low grade squamous intra-epithelial lesions (LSIL) and recorded positive findings. This was a four-center study that included 41 women: 20 in the treatment group and 21 in the control group. The women were treated for 6 weeks with a follow-up at 12 weeks. We showed resolution—meaning that pap smears went from abnormal to normal with no evidence of dysplasia, even upon colposcopy, in just under half of the patients that received treatment versus those patients that received no treatment. It was aggressive therapy and our docs were pretty amazed with the results. This has set the stage for the next phase of trials. That’s the plan. We’re moving to randomized, double-blind, placebo-controlled trials.

OBR: What is your L-DOS47 initiative?
JD: We have developed a product to modify the microenvironment associated with cancer cells. Cancer cells in any given solid tumor exhibit certain traits, including an acidic extra cellular compartment. This compartment has an abnormally low pH level as a result of the metabolic function of cancer cells. Healthy cells, in comparison, are more alkaline in nature. The difference in acidity is thought to play a role in a cancer cell’s ability to invade and metastasize. So we decided to develop a therapeutic that will change that environment from acidic to alkaline.

OBR: Do you have a core technology for that as well?
JD: Yes. DOS47 is the general substance that we want to get to the site of the cancer cell in order to reverse the acidity. To achieve this, we’ve conjugated DOS47 with an antibody fragment specifically designed to target the lungs, and we call it L-DOS47. L-DOS47 is an i.v. product that has incredible specificity for NSCLC cells, and doesn’t bind substantially to healthy tissues or any other cancers for that matter. Once you get DOS47 to the site of the tumor, its activity is extra cellular in action.

Many of today’s compounds have to penetrate the cancer cells in order to function. We’re interested in parking L-DOS47 on the external surface of the cancer cell, where the antigen binding site is for the L-antibody, and then allowing it to cause a biochemical reaction that will modulate the acidity to become alkaline. In addition, L-DOS47 is believed to cause the production of ammonia molecules which readily diffuse into cancer cells and have a cytotoxic effect.

In theory, we think the move from an acidic to alkaline microenvironment has a combination of effects that debilitate the ability of the cancer cell to metastasize and invade. In addition, the cancer cell can’t be supported in an alkaline environment. L-DOS47 is still in the pre-clinical stage, but our goal is to file an IND and move to Phase 1 trials this year.

OBR: Are you looking to partner with your technology?
JD: We’ve already partnered with Schering-Plough to develop Topical Interferon Alpha-2b. With L-DOS47, because of its behavior in reversing acidity and moving to alkalinity, we think there is very strong commercial partnering potential for adjunct application where it would be used with some of the leading therapeutics for NSCLC. We’ll look to evaluate those in time, for now we are coming out of the Canadian woodwork so to speak.

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Compendia: The Bridge Between FDA Approved Indications and Off-label Drug Usage

2008-02-04T10:33:00.000-08:00

On behalf of OBR, author Bryan Cote contacted 1000 oncology practices via a private e-mail survey featuring 10 questions. Disseminated in September 2007, 104 oncology practices responded; of which 68 were practice managers, 21 physicians, 11 pharmacists, and 4 administrative/billing managers. In October, the author followed up with 20 of the 104 respondents by telephone, 14 oncologists and 6 practice managers, to gather more in-depth responses. Following is a discussion from one of the findings.

Roughly 60% of oncology drug usage can be considered off-label, and inefficiencies have been an unfortunate staple of the compendia-based reimbursement process, affecting the entire oncology-care continuum. Armed with evidence that outdated compendia can negatively affect healthcare system costs and care, payers at the federal and commercial level are beginning to respond with policies more favorable to the oncology business. For all their inherent value as a patient access benefit and reimbursement bridge to new FDA approved uses and indications for patients with cancer, drug treatment compendia recommendations and interpretations have at times been as wildly inconsistent as Phil Mickleson’s tee shots.

In a unique move, that if successful could become a model among other payers, United Healthcare (UHC) is expected to adopt the NCCN Drugs and Biologics Compendium and its recommendations as it’s only accepted commercial business compendium. However, endorsing only one compendium carries with it some potential limitations. According to Gerald McEvoy, PharmD, Assistant Vice President of Drug Information and Editor of the American Hospital Formulary Service (AHFS-DI), the NCCN compendium does not carry guidelines for several orphan cancers. Moreover, unlike the AHFS, which updates its compendium monthly and addresses non-oncology uses for cancer drugs, the NCCN's compendium does not.

Is a Single Compendium a Conflict?
“For everyday guidance,” says Myron Goldsmith, MD, who peer reviews oncology treatment plans as chief medical officer for New Century Infusion Solutions, “NCCN keeps incredibly current…but it’s not as evidence-based as ASCO.”

AHFS sees other issues: “NCCN's scope is far more limited than AHFS’s compendium,” says McEvoy. “Notably absent is [its] focus on medication safety.”

The AHFS is published by the American Society of Health-System Pharmacists® (ASHP) with no apparent vested interest in any one patient population or disease. In its comments to CMS on the Medicare Part B proposed rule, the ASHP strongly recommended that safety information be added to its list of desirable characteristics for a drug compendium. However, there was no mention of this in the final Medicare physician fee schedule rule for 2008.

According to the 2008 Medicare physician fee schedule, there is really only one authorized compendia for Medicare in 2008—AHFS—and so CMS is seeking suggestions, using MedPAC criteria to decide which compendia it will use for the Part B program.

Although the 104 responding facilities represent a small segment of the total market, the insight from both practice managers and clinicians give us some ideas of how to improve the compendia business. Compendia is no doubt a key reimbursement ingredient for providers, but with different compendia recommending different guidelines, and payers relying on multiple compendia, payment for anti-cancer treatment is a time consuming puzzle. And, by only having one approved compendium there will be less sources to help in the approval of off-label usage and more hesitancy to prescribe off-label which is a detriment to patients.

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How Does Drug Pricing Drive Therapeutic Choice?

2008-01-28T09:00:00.000-08:00

An expert panel convened in Atlanta, Georgia, December 9th during the 49th annual meeting of the American Society of Hematology. The Biogen Idec-sponsored symposia, titled, “How does drug pricing drive therapeutic choice?” featured presentations from Frank Lichtenberg, PhD, Professor of Business at the Columbia University Graduate School of Business, New York, NY; Sir Michael Rawlins, MD, Chairman of the National Institute of Health and Clinical Excellence, London, United Kingdom; and Peter Bach, MD, Memorial Sloan-Kettering Cancer Center, New York, NY. Linda Bosserman, MD, FACP, President, Wilshire Oncology, Los Angeles, Calif. moderated the panel discussion on the issue of drug pricing.

Pharmaceutical Innovation and Cancer Survival
According to Dr. Lichtenberg, cancer survival rates have increased substantially in the last 50 years. He hypothesized that the development and use of new cancer drugs has made an important contribution to the increase in cancer survival. He tested this hypothesis by examining the relationship between drug vintage (approval year) and cancer survival in four methods of analysis, using four different sets of data.

His analysis revealed that the cancer sites whose drug vintage (measured by the share of post-1990 treatments) increased the most during the 1990s (indicating use of newer drugs) tended to have larger increases in observed survival rates, controlling for other factors…that drug vintage (the share of post-1985 treatments) had a positive and statistically significant effect on both 1-year and 5-year survival rates...that, typically, countries that adopted new cancer agents more rapidly experienced larger declines in their age-adjusted cancer mortality rate…that state reimbursement policies may play a part in cancer survival rates.

The NICE Experience: A total cost of care approach
Sir Michael Rawlins acknowledged Dr. Lichtenberg’s research that 5-year survival rates appeared lower in the UK than in other European countries; however, he emphasized that the UK has recently doubled its investment in healthcare—and these results have intrigued US payers.

Faced with half of the US’s per capita healthcare investment, the UK has chosen to establish a rationing system for allocating healthcare resources. To set limits, NICE weighs a drug’s cost-effectiveness in its coverage decisions and in some cases has said no to paying for certain treatments.

“Sometimes we need to show selective use of a drug, because we’ve felt it’s not cost effective for certain uses,” said Sir Michael.

Of the five oncology treatment-condition pairs NICE has rejected for use since 1999, three were cost-ineffective. “In Britain, the truth is the population doesn’t like the idea of cost coming into the decision, [but] it’s clear we have to do it,” concluded Sir Michael.

How to Pay for Cancer Drugs
Peter Bach, MD, acknowledged that drug prices can be perceived as too high. He offered a mix of regulatory and policy solutions to control prices, while maintaining choice, including:

• Create a forum similar to NICE’s approach to value-based payment.
• Give patients more of an incentive to spend healthcare dollars efficiently.
• Regulators could set prices and pay a fixed amount per healthcare gain.
• Change the sole-source definition for Medicare’s average sales price purposes.

Note: A full length version of this article was published in the January issue of OBR.

Download a full-length PDF of this article

View a webcast of this symposium sponsored by Biogen Idec

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The Appeal of Genasense: The drug, the data, and the tangled web that its FDA review has become

2008-01-14T21:19:00.000-08:00

At some point—probably in the very near future—there will be a final decision by the U.S. Food and Drug Administration (FDA) about whether Genta’s antisense agent Genasense® (oblimersen sodium) will be approved for the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL). In the meantime, the review process has become an increasingly tangled web of data, assertions, and upset. Many healthcare professionals feel that the drug warrants approval and that the FDA’s treatment of Genasense has been too harsh.

Among the concerns raised by the ODAC members was their preference for progression-free survival (PFS) as an endpoint. The committee also asserted that the patients likely to benefit had not been clearly identified, and that the potential number of patients who would benefit did not warrant the approval of an expensive drug.

According to Genta, and many CLL experts, the FDA’s rejection of Genasense at that time was, simply, wrong. Patients have voiced their concerns, too.

According to the most recent findings (ASH abstract 751), which have been submitted to the FDA as part of the appeal, patients in the triple combination arm achieved a complete response (CR) rate of 17 percent, compared with a CR rate of 7 percent among patients treated with chemotherapy alone, a statistically significant difference.

The new data may be enough to warrant approval by the FDA. But the larger question of whether the agent should have been approved in the first place still looms, as do issues other than data that may have influenced the original decision.

Regardless of the outcome, the saga of Genasense raises crucial questions about the FDA review process. These issues extend well beyond this one drug: as is widely known, the FDA review of Dendreon’s immunotherapy Provenge® is now under serious investigation.

In its genuine efforts to ensure drug safety, is the FDA preventing drugs from reaching the patients who could be helped? Are there political reasons behind the FDA’s decisions to approve or reject drugs, and if so, what are they? Are drug applications such as these being used to set a precedent, rather than being evaluated for their own merit? Is the FDA weighing cost too heavily in its considerations of benefit?

Numerous CLL patients have already been helped by Genasense, and there is a clear desire among experts and patients alike that this drug be made available. At some point, the outcome of the Genasense application will be made clear. But its hard-to-treat side effects—the questions and issues raised during the review process—remain.

Note: A full length version of this article was published in the January issue of OBR.

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