Tracking And Interpreting OBR Data in August 08

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

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?

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?”