Aveo Pharmaceuticals Inc. (AVEO:US) failed to win the backing of U.S. regulatory advisers for its lead product candidate, a kidney cancer drug, after the panelists questioned whether it was as effective as existing treatments.
Members of the Food and Drug Administration advisory panel expressed concerns that a final-stage trial showed Aveo’s tivozanib may reduce survival compared with Bayer AG (BAYN) and Onyx Pharmaceuticals Inc. (ONXX:US)’s Nexavar. Aveo was criticized for relying on a single-final phase clinical trial and the panel said the company should conduct another study to better assess the benefits.
The FDA is scheduled to decide by July 28 whether to approve tivozanib, a drug that may generate sales of $205 million in 2016 for Cambridge, Massachusetts-based Aveo, according to the average of three analysts’ estimates compiled by Bloomberg. The advisers today voted 13-1 that Aveo hadn’t demonstrated the medicine’s benefits outweigh the risks.
“I cannot picture how I would talk with a patient about putting him or her on tivozanib, allowing them to live without progression longer but possibly to die faster,” Mikkael Sekeres, panel chairman and associate professor of medicine staff at the Cleveland Clinic’s Taussig Cancer Institute, said during the meeting today in Silver Spring, Maryland.
Aveo shares were halted during the meeting. The company shares plunged 31 percent on April 30, when FDA staff said in a report that the drug may need another clinical trial.
“We remain confident in the efficacy, safety and tolerability of tivozanib,” Tuan Ha-Ngoc, Aveo’s president and chief executive officer, said in a statement. While disappointed in the recommendation, he said the company would “work closely with the FDA to address the issues discussed by the panel today as the agency continues its ongoing review.”
Richard Pazdur, director of the FDA’s Office of Hematology and Oncology Products, criticized Aveo for doing the single trial that wasn’t conducted in a way to determine overall survival without uncertainty. The FDA has been confounded by the application for months, he said.
“We’re having a difficult time as to why we should accept this uncertainty here,” Pazdur said.
Other drugs in the same class were approved based on a single trial focused on improved survival time without the disease progressing rather than total survival, William Slichenmyer, Aveo’s chief medical officer, said in an interview prior to the April 30 report. Tivozanib showed a benefit on disease progression.
Other drugs in the same class include Nexavar, Pfizer Inc. (PFE:US)’s Sutent and GlaxoSmithKline Plc (GSK)’s Votrient.
There are about 59,000 new cases of renal cell carcinoma diagnosed in the U.S. each year and about 25 percent are advanced at the time of diagnosis, Slichenmyer said. About 12,000 patients with the disease die each year.
Aveo sold $81 million of shares in an initial offering three years ago to help fund research on the drug, which is intended to treat advanced renal cell carcinoma.
Patients taking tivozanib lived a median 11.9 months without the disease worsening versus a median 9.1 months for those on Nexavar, Aveo and Tokyo-based Astellas Pharma Inc. (4503) said last year in a statement. Patients on the pill lived a median 28.8 months compared with a median 29.3 months for patients on Nexavar, according to the study Aveo is relying upon in its application for FDA approval.
Tivozanib didn’t have the desired outcome on survival because patients in the clinical trial whose cancer got worse while taking Nexavar were allowed by researchers to switch to tivozanib, Slichenmyer said. The crossover resulted in the comparison of two sequential drugs versus only tivozanib.
Tivozanib is highly potent and targeted, causing fewer side effects such as diarrhea and a painful skin condition on the hands and feet that result from chemotherapy, Slichenmyer said. The most common reported side effect for patients on tivozanib was high blood pressure.
If approved, Aveo would lead marketing of tivozanib in North America and Astellas would handle the effort in Europe.
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