Aveo Pharma: 'Crossover' Ate My Kidney Cancer Drug Survival Benefit

Updated with stock price.

CAMBRIDGE, Mass. ( TheStreet) -- Final overall survival results from the phase III study of Aveo Pharmaceuticals' ( AVEO) kidney cancer drug tivozanib were released Tuesday night, and as expected, tivozanib-treated patients were at a greater risk of death than those treated with Onyx Pharmaceuticals' ( ONXX) Nexavar.

At the median, the difference in survival was just two weeks. Tivozanib-treated patients reported a median overall survival of 28.8 months compared to 29.3 months for Nexavar patients.

However, when overall survival in the study was analyzed over two years, the relative risk of death was 25% higher in the tivozanib arm relative to the Nexavar arm. Hazard ratio = 1.245. While survival trended against tivozanib, the greater risk of death was not statistically significant.

Aveo has struggled for months to assuage investor concerns about the confounding results from the tivozanib study in advanced kidney cancer patients. Tivozanib met the primary endpoint of the study by delaying tumor regrowth by almost three months more than Nexavar (11.9 months vs. 9.1 months.) However, this significant improvement in progression-free survival favoring tivozanib did not help patients live longer.

Last August, shares of Aveo fell from $14 to $8 when the company first disclosed FDA's concerns about the confounding survival analysis from the tivozanib trial.

Aveo shares closed Tuesday at $7.89 but were down 11% to $7.04 in early Wednesday trading.

Aveo believes overall survival of tivozanib was snake bit by a study design that allowed patients treated initially with Nexavar to receive effective, subsequent therapy, including tivozanib. Of the 257 patients who started the study on Nexavar, 74% "crossed over" to receive treatment with other kidney cancer drugs, including tivozanib and other so-called VEGF therapies like Pfizer's ( PFE) Sutent or GlaxoSmithKline's ( GSK) Votrient.

By comparison, 36% of the patients treated initially with tivozanib went on to receive additional kidney cancer drugs, including 10% who received subsequent VEGF therapies.

In certain smaller subsets of patients, overall survival trended in favor of tivozanib over Nexavar, the opposite of what occurred in the study as a whole. Some of these alternate survival analyses were pre-defined in the study's statistical analysis plan, while others were not, a company spokesman said.

Tivozanib is under FDA review, with an approval decision expected by July 28.

To bolster the supportive case for approval, Aveo is also expected to point to other analyses from the phase III trial supporting tivozanib's efficacy in kidney cancer patients. Treatment with tivozanib following Nexavar resulted in a median progression-free survival of 8.4 months and a tumor response rate of 13%. Tivozanib-treated patients reported fewer side effects dose reductions than patients treated with Nexavar, but this did not translate into a significant difference in quality of life scores between the two drugs.

The median overall survival of 28.8 months reported by tivozanib-treated patients is similar to survival rates of competing kidney cancer drugs. In a recent study comparing Glaxo's Votrient to Pfizer's Sutent, median overall survival was 28.4 months and 29.3 months, respectively. Aveo has only compared tivozanib directly against Nexavar but is conducting another study right now that pits tivozanib against Sutent.

Multiple presentations of data from the tivozanib phase III study in kidney cancer are being presented later this week at the American Society of Clinical Oncology Genitourinary Cancers Symposium.

If FDA approves tivoazanib, it will be the ninth drug marketed for kidney cancer and the fifth drug to share a similar mechanism of action. Sutent has been the market-leading kidney cancer drug but has recently lost ground to Votrient.

-- Reported by Adam Feuerstein in Boston.

Adam Feuerstein writes regularly for TheStreet. In keeping with company editorial policy, he doesn't own or short individual stocks, although he owns stock in TheStreet. He also doesn't invest in hedge funds or other private investment partnerships. Feuerstein appreciates your feedback; click here to send him an email.

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