Aveo Oncology (NASDAQ: AVEO) has seen its share of ups and downs over the past year as it has fought to prove the worth of its kidney cancer drug, tivozanib. Now the moment of truth is at hand, with an independent advisory panel choosing whether to recommend the drug to the FDA.
On Thursday, the 13-member Oncologic Drugs Advisory Committee will make its recommendation to the FDA on whether tivozanib should be cleared for sale in the U.S. market. It’s a true high-stakes moment for Cambridge, MA-based Aveo, as the drug represents its first and closest shot at commercial success after 11 years of R&D.
Aveo wants the FDA’s nod to treat patients with renal cell carcinoma, or kidney cancer. There could be quite a bit amount of debate about Aveo’s application at Thursday’s hearing. Today, the FDA released briefing documents that its staff has provided to members of the committee, and investors didn’t like what the FDA staff had to say. Shares of Aveo fell more than 25 percent today to $5.56 at 1:50 pm Eastern time today.
In those papers, the FDA expressed concern with Aveo’s 517-patient study, TIVO-1, which compared the drug to Onyx and Bayer’s sorafenib (Nexavar). The FDA staff noted, for example, that most of the patients dosed with tivozanib did so at testing sites in Central and Eastern Europe. As such, those patients didn’t get the second-in-line therapies those patients typically would have received in U.S., because they simply weren’t available.
That could skew Aveo’s results in determining how long patients ultimately lived after taking its drug, leading the FDA to question whether Aveo needs to run another study to better determine tivozanib’s benefits before it gets the green light.
“Given the uncertainty in overall survival, and availability of multiple therapies, is another trial needed to better characterize the risk-benefit profile of tivozanib before approval can be considered?” reads the FDA’s draft question for the panel.
RBC Capital analyst Adnan Butt agreed that Aveo faces a daunting task Thursday, albeit not an impossible one. Here’s what he wrote in a note to clients Tuesday:
“The argument now rests in Aveo’s hands to make a compelling argument to sway the AdCom’s hand as to why patients would benefit from having access to tivozanib before vs. after another study is done. We still think it can draw a favorable picture on safety and then on [progression free survival, or PFS] but the bar is admittedly higher. We think tivozanib could squeak through but believe another [late-stage] study would be recommended.”
He added that the FDA could still call for another study after approval, if the committee votes in favor of tivozanib.
Tivozanib is a once-daily pill that works by cutting the blood flow to tumors. It does so by blocking the three types of VEGF receptors, which are markers on the surface of cancer cells.
Aveo is applying that tumor-fighting power to kidney cancer, where the company hopes tivozanib can bust into a crowded field that includes sorafenib, Pfizer’s sunitinib (Sutent) and axitinib (Inlyta), GlaxoSmithKline’s pazopanib (Votrient), and Roche/Genentech’s bevacizumab (Avastin). There is certainly room for tivozanib to grab hold: there are expected to be roughly 65,150 new cases of kidney cancer in 2013 in the U.S. alone, according to data from the American Cancer Society.
Aveo pitted the drug against sorafenib in its TIVO-1 study, and the results were decidedly mixed.
Aveo itself trumpeted the study as a success, and in the sense that the drug met its primary goal of keeping tumors from spreading in patients longer than sorafenib while proving safer and easier to use, it was. Specifically, tivozanib kept tumors from spreading for a median time of 11.9 months, compared with 9.1 months for those randomly assigned the drug from Onyx/Bayer.
In addition, fewer patients taking tivozainb reported side effects such as skin rash, hair loss, and diarrhea, than those taking sorafenib. A smaller number also ended up having to take unscheduled drug “holidays,” or dose reductions, because of severe side effects.
All of which painted a rosy picture for Aveo. But things became much murkier when Aveo revealed in August that the FDA raised concerns about how long patients who were taking the drug ultimately lived. In the same study, 81 percent of those taking sorafenib were alive after one year, compared to 77 percent of the people who took tivozanib (the median overall length of survival for patients taking sorafenib was 29.3 months, compared to 28.8 months for those taking tivozanib).
Aveo has argued that the data is a bit skewed by the fact that about 53 percent of the patients in the group that took sorafenib moved on to get a subsequent therapy after their disease progressed, and in most all of those cases, that therapy was tivozanib.
Just 17 percent of the patients taking tivozanib received a follow-up therapy thereafter, raising the distinct possibility that the first group benefited from Aveo’s drug.
Aveo will hold a conference call discussing the results of the hearing Thursday.