FDA panel votes against Aveo's kidney cancer drug

Thu May 2, 2013 1:48pm EDT

A view shows the U.S. Food and Drug Administration (FDA) headquarters in Silver Spring, Maryland August 14, 2012. Picture taken August 14, 2012. REUTERS/Jason Reed

A view shows the U.S. Food and Drug Administration (FDA) headquarters in Silver Spring, Maryland August 14, 2012. Picture taken August 14, 2012.

Credit: Reuters/Jason Reed

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(Reuters) - An advisory panel to the Food and Drug Administration recommended that the agency reject a kidney cancer drug made by Aveo Pharmaceuticals Inc and Astellas Pharma Inc, saying data from the clinical trial were inconsistent.

In a 13-1 vote on Thursday, the panel said Aveo had not shown that the drug's benefits outweighed its risks in a well-controlled study, and said a second trial would be needed before the drug, tivozanib, should be approved.

Aveo's shares fell as much as 57 percent on Thursday.

Aveo and Astellas said that while they were disappointed with the outcome of the meeting, "we remain confident in the efficacy, safety and tolerability of tivozanib," and would work with the FDA to address the issues raised by the panel.

Tivozanib delayed progression of the disease in a 517-patient trial, but patients taking the drug did not live longer than those who took a rival treatment, Nexavar, known generically as sorafenib. Nexavar is made by Bayer AG and Onyx Pharmaceuticals.

The FDA pointed out that while the drug conferred a 20 percent benefit in delaying disease progression, it increased the risk of death by 25 percent. Patients in the tivozanib arm of the trial lived 28.8 months while patients taking sorafenib lived on average 29.3 months.

"If we approve this drug based on this study how would we communicate to patients the potential 25 percent increase in the risk of death?" Jonathan Jarow, Medical Officer at the FDA, asked the panel.

Representatives from Aveo argued that the drug met the main goal of the trial, and they argued that negative overall survival figures were because patients in the Nexavar arm were allowed to cross over into the tivozanib trial. In effect, they said, tivozanib was compared against a two-drug regime.

Jarow countered that there are seven other approved drugs to treat renal cancer on the market, and patients were allowed to cross over in five of those trials, "yet none of these trials demonstrated a negative trend for overall survival," he said.

Panelists expressed concern that most of the patients in the trial were studied in central and eastern Europe and they questioned whether the results would be applicable to the U.S. population.

Why, demanded Dr. Richard Pazdur, director of the FDA's cancer division, did Aveo conduct its clinical trials in central and eastern Europe? If tivozanib was such a promising product, why were clinicians in the United States not clamoring to enter their patients?

Aveo responded that at the time it was enrolling patients, a number of other companies were also enrolling patients in competing trials, forcing Aveo to recruit most of its patients oversees.

One panel member, Lori Dodd, a mathematical statistician with the National Institutes of Health, said she was "angry" at what she perceived to be a sloppy design trial which potentially denied kidney cancer patients access to a new drug.

"I think if the trial had been conducted in a better way we would not be here," she said.

Pazdur also said he was "extremely disappointed" in the information Aveo proposed placing on the drug's label, which he said did not provide patients with the crucial survival data.

Aveo's shares were halted prior to the meeting. They closed on Wednesday at $5.25, having fallen from a year high of $14.08 last July. They fell roughly 27 percent alone on Tuesday after the FDA released its initial impressions of the data.

Aveo's shares fell 47 percent to $2.76 in Thursday afternoon trading on Nasdaq, after briefly slipping as low as $2.25.

(Reporting By Toni Clarke in Washington; Editing by Maureen Bavdek, Sofina Mirza-Reid and Chris Reese)

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Comments (2)
MD9 wrote:
It’s a very interesting meeting for the following reasons:
1) It looks like the FDA agreed that Overall-Survival (OS)rate, a parameter that can be affected by many other factors in life, was not necessary for regulatory decisions. Many other drugs in the same category were approved based on the same primary measure that this company studied. But, it’s now critical for this drug to show OS is good. (I wonder what would have happened if the sponsor didn’t even study this as the secondary outcome per FDA’s previous suggestion).
2) In the labeling of the comparison drug S, FDA didn’t even bother mentioning the detail of OS in its Clinical Study section. It mostly mentioned the other outcome Progression-free Survival (PFS) rate. But I guess, for this Aveo’s drug, FDA is considering a new stardard now.
3) The company presents the details of those death cases from disease progression related to the study drug T: most died after 12 months from desease progression, not to mention the baseline characteristics of this study drug T group had more severe cancer disease and larger tumors than the comparison group. But it seems nobody cares, not even the panel nor the FDA director – were they daydreaming when the company was presenting?
4) Better design? The standard is to have placebo-controlled double-blind randomized study. Is it ethical to do that in such patient with aggressive cancer?

May 02, 2013 1:07pm EDT  --  Report as abuse
MD9 wrote:
I feel sorry for those patients who have benefited from this drug.

Single trial is not uncommon in cancer drug regulation. Many clinical trials don’t have sufficient minority populations. But, the panel members would rather ignore the current patients benefits and independent speakers’ (not paid by the company) requests, it’s blowing my mind. I wonder if the same would ever happen if the minority group happens to be Asian American or others.

May 02, 2013 1:14pm EDT  --  Report as abuse
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