Oncology Business Review

Tracking And Interpreting OBR Data in August 08

noreply@blogger.com (Don Sharpe - www.oncbiz.com) — Thu, 04 Sep 2008 22:51:00 +0000

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

noreply@blogger.com (Don Sharpe - www.oncbiz.com) — Mon, 09 Jun 2008 18:10:00 +0000

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?

noreply@blogger.com (Don Sharpe - www.oncbiz.com) — Sat, 31 May 2008 00:26:00 +0000

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

noreply@blogger.com (Don Sharpe - www.oncbiz.com) — Tue, 20 May 2008 17:18:00 +0000

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

noreply@blogger.com (Don Sharpe - www.oncbiz.com) — Thu, 15 May 2008 18:34:00 +0000

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

noreply@blogger.com (Don Sharpe - www.oncbiz.com) — Mon, 12 May 2008 16:25:00 +0000

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?

noreply@blogger.com (Don Sharpe - www.oncbiz.com) — Tue, 11 Mar 2008 17:44:00 +0000

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

noreply@blogger.com (Don Sharpe - www.oncbiz.com) — Wed, 05 Mar 2008 06:08:00 +0000

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

noreply@blogger.com (Don Sharpe - www.oncbiz.com) — Thu, 21 Feb 2008 18:47:00 +0000

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

noreply@blogger.com (Don Sharpe - www.oncbiz.com) — Mon, 11 Feb 2008 05:27:00 +0000

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

noreply@blogger.com (Don Sharpe - www.oncbiz.com) — Mon, 04 Feb 2008 18:33:00 +0000

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?

noreply@blogger.com (Don Sharpe - www.oncbiz.com) — Mon, 28 Jan 2008 17:00:00 +0000

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.

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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

noreply@blogger.com (Don Sharpe - www.oncbiz.com) — Tue, 15 Jan 2008 05:19:00 +0000

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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Biogen Idec: An Oasis for Employees During the Southern California Wildfires

noreply@blogger.com (Don Sharpe - www.oncbiz.com) — Sat, 12 Jan 2008 18:03:00 +0000

With wildfires threatening Southern California families and their homes, Biogen Idec opened its campus facilities to ease the burden of their employees who were in the fires’ path of destruction. By Candice J. Bruce, PhD

The wildfires that ravaged southern California in late October 2007 halted business-as-usual at many of the over 500 biotech companies in San Diego County. The fires moved in on Sunday, October 21 and by Monday morning there were eight fires fueled by strong Santa Ana winds that derailed firefighters’ efforts to stop them. Biotech centers in Carmel Valley, Sorrento Valley, and Carlsbad as well as their adjacent neighborhoods, which house many of the 36,000 people employed in the San Diego biotech industry, were in jeopardy.

Several biotech companies and academic institutions were closed due to the looming threat of the approaching wildfires. Recognizing the seriousness of the situation and that many of their employees would be affected by the fires, Biogen Idec’s San Diego facility opened up its campus to displaced employees without hesitation. Over 30 percent of Biogen Idec’s employees had been evacuated and many of them along with their families and pets spent the night at the campus hoping their home would be spared. To try and make everyone as comfortable as possible, “the catering staff stayed on and prepared meals; blankets and pillows were provided as well as books and DVDs for the kids,” said Naomi Aoki, director of corporate communications for Biogen Idec.

Jorg Thommes, director of purification process development at Biogen Idec, evacuated his home during the wildfires; he and his family spent the night at the campus. His children were frightened by the fires, but “when we arrived at Biogen Idec they saw some of their friends and became happier so my wife and I became more comfortable. We were deeply impressed with the company’s commitment and concern for us. A few days after we returned home, my daughter asked when the next sleepover at daddy’s work would be.”

Over 300,000 people in San Diego County had been forced to flee their homes. Biogen Idec kept its campus open for the displaced employees and was able to secure hotel rooms for many of them. Concern for the welfare of the evacuees led to a group being formed to make sure that employees were aware of resources available to help them, and many employees not affected by the fires opened up their homes to those that needed a place to stay. Annie Glidden, head of the relief effort at Biogen Idec, stated, “I was amazed by the unquestioning commitment for employee safety and well-being coming from everyone at Biogen Idec in San Diego as well as our other locations. Everyone came together on behalf of the people affected by the fires, and it was something that I had not experienced before at a company.” Biogen Idec was closed for business the entire week of October 22 and employees were paid in full.

Overall the wildfires burned more than 300 square miles and destroyed over 1000 homes in San Diego. The economic impact is estimated to be over $1 billion in San Diego County alone. Numerous biotech companies including Genentech, Invitrogen, Althea Technologies, and Biogen Idec as well as others have donated hundreds of thousands of dollars to various fire relief funds. Biogen Idec has donated $50,000 to Habitat for Humanity as well as other funds and is organizing a team to work with the organization to rebuild a home.

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Looking Back; Thinking Forward

noreply@blogger.com (Don Sharpe - www.oncbiz.com) — Thu, 03 Jan 2008 23:16:00 +0000

Cancer Drug Development and the Orphan Drug Act by
Michael Scott, Prinicipal and Executive VP,voxmedica

Friday of last week was the 25th anniversary of the signature of the Orphan Drug Act (ODA) by Ronald Reagan -- on January 4, 1983.

Since the signature of this Act, over 300 drugs have been approved in the US with orphan drug designations, and about 60 of those have been cancer therapeutics. If you add the other drugs approved with orphan designations that are used in supportive cancer care, the number is nearer to 80. The first cancer therapy approved with an orphan designation appears to have been methotrexate for osteogenic sarcoma in April 1988; the most recent, a second orphan indication for Nexavar (sorafenib), for hepatocellular carcinoma, in November 2007. Gleevec (imatinib) has now accumulated seven orphan indications in the US alone.

Arguably, the passage of the ODA has been one of the most successful pieces of legislature approved by Congress in the past 30 years. In the decade before its approval, only 10 new drugs developed by the pharmaceutical industry had been approved for orphan diseases. Passage of the ODA has led to an explosion in the number of drugs available for rare forms of cancer, has facilitated the continuing transformation of the global biotechnology industry (with a particularly successful emphasis on the area of oncology), and has led to similar orphan drug legislation in many other countries around the world.

Late last year, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) developed a single application process for orphan drug designation that would be valid for both agencies (see the joint EMEA and FDA press release dated November 26, 2007). This will simplify the process of gaining orphan designation across a dozen of the world’s major pharmaceutical markets. In addition, as we gain greater insight into the precise subtypes of various cancers that are responsive to particular agents, almost every form of cancer is potentially an orphan disease, with major implications for the regulatory development pathways for cancer therapeutics over the next decade.

From the payer perspective, one of the downsides of this success has been the sudden increase in prices for highly effective orphan cancer drugs with relatively small markets. In the past couple of years, the introductions of Erbitux (cetuximab), Revlimid (lenalidomide), Sprycel (dasatinib) and other orphan cancer therapeutics have been associated with high treatment costs for patients and payers. The degree to which this trend is sustainable is one that will tax minds of biopharmaceutical companies and payers for years to come. On the other hand, as effective treatments become more widely available for highly defined patient populations, is it ethical for societies to deny treatment on the basis of cost alone?

How do you think the continuing evolution of the use of the ODA will affect cancer therapy? Can we afford all these niche therapeutics? Does your company really appreciate how to best take advantage of orphan drug designation and relevant regulatory issues? Contribute to the OBR blog on this topic.

And while we are at it, congratulations to the National Organization for Rare Diseases (NORD), whose retiring president, Abbey Meyers, is widely recognized as the primary consumer advocate behind the original approval of the ODA. NORD is also 25 years old this year, and has planned a series of special events to celebrate the joint anniversary.