Biotech Stock Mailbag: Aveo, Anthera, Amarin, MAP Pharma
BOSTON ( TheStreet) -- Happy Thanksgiving! An early Biotech Stock Mailbag:
Nico asks, " Aveo Pharmaceuticals (AVEO) has to be oversold at this point, right? Is FDA likely to make a big stink about a small unfavorable trend in 1-year overall survival data even though (a) median OS has not yet been reached; (b) all kidney cancer drug approvals have been based on progression-free survival (PFS) and tivozanib showed the single-highest PFS ever shown in a phase III clinical trial; and (c) the overall survival trend is easily explained by the crossover trial design."
Aveo is a cautionary tale in oncology drug development. The company deserves huzzahs for running a pivotal study in kidney cancer comparing tivozanib against an active comparator -- Onyx Pharmaceuticals' (ONXX) Nexavar. We see far too few clinical trials that compare one active drug against another.
Unfortunately, the mixed data that emerged from Aveo's tivozanib study have raised a lot of uncomfortable questions and caused the company a ton of trouble, which may explain why head-to-head drug studies are so rare.
Tivozanib delayed the time before patients' kidney cancer started to grow (progression-free survival) by a median 11.9 months compared to 9.1 months for Nexavar -- a difference that was statistically significant and which achieved the study's primary endpoint. Tivozanib was also better tolerated than Nexavar, with fewer dose reductions and treatment discontinuations due to adverse events.
But (and you knew this was coming), the analysis of overall survival -- a key secondary endpoint in the study -- was problematic. At one year, 81% of Nexavar patients were still alive compared to 77% of tivozanib patients. A second look at overall survival conducted a two years yielded a similar result.
Aveo believes survival trended against tivozanib because more than 60% of the patients randomized to the Nexavar arm "crossed over" to receive tivozanib or some other therapy upon tumor progression. These Nexavar crossover patients are living longer because they benefited from treatment with two active kidney cancer drugs, Aveo argues. Meantime, only 24% of patients chosen to begin the trial in the tivozanib arm went on to a subsequent therapy.
This explanation of the wrong-way survival benefit makes sense but FDA will be the ultimate arbiter. The agency has "expressed concern" with the survival trend analysis and has told Aveo to expect these data to be considered during the agency's tivozanib review, according to the company's regulatory filings.
Here's the risk statement in Aveo's 10-Q that freaked out investors:
"Overall survival is a key secondary endpoint in our phase 3 clinical trial. Based on our early discussions with the FDA, we do not expect the FDA to require that we show a statistically significant improvement in overall survival in patients treated with tivozanib in order to obtain approval by the FDA... The FDA has expressed concern regarding the overall survival trend in the TIVO-1 trial and has said that it will review these findings at the time of the NDA filing as well as during the review of the NDA."