14-Jan-08 13:32 Dendreon’s prostate cancer vaccine Provenge likely to fail mid-year interim analysis, industry experts speculate
by Kimberly Ha and Sasha Damouni
Story Dendreon’s results on prostate cancer vaccine Provenge seem to be headed towards mid-year interim failure, industry sources speculated. Provenge is a patient-specific stem cell therapy which represents a potential first-in-class treatment for advanced prostate cancer.
Dendreon’s Phase III IMPACT trial has completed enrolment of more than 500 patients, and interim data is expected mid-year. Final data on overall survival is expected in 2010. The primary endpoint is overall survival in men with metastatic hormone-refractory prostate cancer. The underlying technology is based on recovery of dendritic cells from each individual patient, and re-infusion of the treated cells to stimulate immune response against tumour cells.
A hedge fund portfolio manager remained adamant that nothing positive would come out of the mid-year interim data. “No way will there be positive data, and not in 2010, which is another story,” he said. Jeff Morhet, CEO of Innexus Biotechnology, added that since cancer vaccines are personalized medicines, each patient has to receive an individual biopsy. “It is hard to convince the cost of goods to the FDA which is currently in lock-down mode. That’s the biggest problem [cancer] vaccine companies have run up against,” he argued.
In recent news, Genitope’s cancer vaccine MyVax for patients with follicular B-cell non-Hodgkin's lymphoma missed its primary endpoint and was ultimately rejected by the FDA. Shares fell approximately 80% in light of the bad news. MyVax failed to improve progression-free survival in patients compared to placebo.
On the insurance front, the adoption of personalized medicine also remains a hurdle. In reality, “you have to realise what makes it through the FDA,” said Morhet. He said he believed FDA acceptance on cancer vaccines was still two years away. “Although cancer vaccines are incredibly exciting, I don’t think the FDA is ready for them. I don’t think the statistics from the data to the FDA will be enough,” he added.
One industry banker said he believed Provenge would get approved, but the question is timing. “Before that you have a couple immunotherapy drugs, like the antibody drugs they said they were never going to get approved 15 years ago,” the banker said. Critics have said that personalized cancer vaccines will have a tough manufacturing process, similar to the current manufacture of antibodies, he said.
The industry banker said Northwest Biotherapeutics received approval for its personalized cancer vaccine treatment in Switzerland. Northwest’s dendretic-cell vaccine, DCVax-Brain for the treatment of brain cancer, delayed recurrence of tumors by 18.1 months in new patients.
Dr Joanne Kurtzberg at Duke University’s pediatric stem cell transplant program, said the FDA does not currently regulate transplantation. “The FDA probably haven’t figured out a developmental strategy for vaccines. That’s a real deficit,” she said. She agreed that a lot of cancer vaccines in development have been rejected.
Dr John Gotto, a senior consultant at SommaTech Consulting Group, said patients suffering from prostate cancer and desperate for treatment may naturally see the benefit claimed by Dendreon and not comprehend the failure of FDA to approve the product. They hold the view that the FDA is insensitive to medical needs and that its Advisory Committee is possibly corrupted by financial conflicts of interest, he added.
"The FDA response was considered controversial, partly because it was viewed as an apparent denial of a potentially effective treatment in an area of great unmet medical need,” said Gotto.
California-based Pharmacyclics CEO, Dr Richard Miller, said for cancer vaccines in general, “there has to be some tangible evidence. And it's a very new field. It's getting to point where the FDA has to work with these companies and come up with endpoints,” he said.
Pharmacyclics lead cancer drug Xcytrin was recently rejected by the FDA, and the company has submitted an application under a protest procedure to the agency. Miller criticized the FDA for not keeping “up to date” with current technology when evaluating data on the cutting edge of science. “They use outdated procedures and methods to evaluate data,” he said.
Dendreon clearly failed to satisfy both primary and secondary endpoints. The FDA took the position that the data were insufficient, as the trial failed to meet its endpoints. “The concerns of patient advocates about the withholding of potentially beneficial treatment are certainly understandable, but ultimately they result from an incomplete understanding of the technical aspects of clinical trial design and statistical analysis,” said Gotto.
Post-Vioxx, the FDA is sometimes accused of having dramatically changed its procedures and expectations regarding safety. Cumulatively, these changes represent an additional and unreasonable burden for drug developers. However, Gotto said the failure to approve Provenge primarily rests on questions of demonstration of efficacy.
“Cancer vaccine. It’s a nice idea,” said Miller.
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