FDA staff question whether Aveo drug needs new trial

n">Staff reviewers for the Food and Drug Administration have asked a panel of outside medical experts whether another clinical trial is needed before an experimental kidney cancer drug made by Aveo Pharmaceuticals Inc and Astellas Pharma Inc can be approved.

The question, posed in documents posted to the FDA's website on Tuesday, caused Aveo's shares to plummet as much as 26.7 percent on Nasdaq.

The reviewers noted that in a late-stage trial, patients taking the drug, tivozanib, did not live longer than those who took a rival product. They asked the panel to consider whether a new trial was needed to better assess risk versus benefit, given that other treatments are available.

The panel will discuss tivozanib, which is designed to treat patients with advanced renal cell cancer, on Thursday and advise the FDA on whether it should be approved based on the current available information.

A clinical trial of 517 patients showed that tivozanib delayed worsening of the disease by an average of 11.9 months compared with 9.1 months for Nexavar, a drug known generically as sorafenib that is made by Bayer AG and Onyx Pharmaceuticals. The result met the main goal of the trial.

Still, patients taking tivozanib did not, on average, live longer than those taking Nexavar. On average, patients in the tivozanib arm of the trial lived 28.8 months while patients taking sorafenib lived on average 29.3 months.

Drug industry analysts provided mixed interpretations of the reviewers' questions.

"We believe the tone of the briefing documents and the question posed to the panel are consistent with our prior work, where we were unable to find historical precedent of the FDA approving an agent with a detrimental overall survival trend," said Howard Liang, an analyst at Leerink Swann.

Salveen Richter, an analyst at Canaccord Genuity, concurred.

"We see considerable risk of a negative panel," he said in a research note.

Others were less pessimistic, saying that while the panel is likely to focus on the overall survival figures, the main goal of the trial was to show a statistically significant improvement in progression-free survival, the time before the disease worsens. The company achieved that goal.

In patients who had not previously received a similar therapy, tivozanib delayed worsening of disease by an average of 12.7 months.

"After review of the documents, we continue to believe there is a good likelihood of a favorable vote," said Geoff Meacham. "Net-net, we would be buyers ahead of the panel."

The trial showed that only 18 percent of tivozanib patients needed dosing interruptions due to side effects, compared with 35 percent for Nexavar. Patients taking tivozanib had a higher incidence of high blood pressure and fatigue, while those who received Nexavar in the study reported a higher incidence of diarrhea and hand-foot syndrome, a skin condition that resembles sunburn and can cause pain and swelling.

Advanced kidney cancer is the ninth most commonly diagnosed cancer in the United States, Aveo said, with an estimated 65,000 new cases projected to be diagnosed this year.

Tivozanib is a pill that is designed to block three members of the vascular endothelial growth factor (VEGF) family of proteins. Blocking VEGF acts to starve tumors of the blood supply and nutrients they need to survive.

The drug is also being studied in a range of other cancers, including metastatic colorectal cancer and metastatic breast cancer. Analysts on average expect the drug to generate annual sales of $1.23 billion by 2017.

In 2007, Aveo licensed the development and commercialization rights to tivozanib outside Asia from Kirin Brewery, now called Kyowa Hakko Kirin. Kyowa retained development and commercialization rights in Asia.

Four years later Aveo and Astellas agreed to co-develop tivozanib outside Asia. The two companies agreed to jointly share in the costs and profits of developing the drug in North America and Europe. Outside these regions, Astellas is responsible for development and commercialization costs and will pay Aveo royalties on sales in those territories.

Aveo's shares fell 26 percent in Tuesday afternoon trading to $5.48 on Nasdaq. Earlier they fell as low as $5.45.

(Reporting By Toni Clarke in Washington; editing by Sofina Mirza-Reid and Grant McCool)