A day after disclosing that US regulators formally rejected their kidney cancer drug application, top Aveo Pharmaceuticals Inc. executives on Tuesday took the unusual step of publicly defending their clinical trials and contending the drug is an effective kidney treatment.
In a conference call with industry analysts, leaders of the Cambridge biotechnology company asserted they had been open in their dealings with the Food and Drug Administration, the federal agency that, according to Aveo, branded the company’s late-stage clinical trial results “uninterpretable and inconclusive when making a risk-benefit assessment.”
Even when FDA regulators suggested another clinical study, Aveo executives said, they did not tell the company that initial approval of tivozanib — its experimental drug for renal cell carcinoma — would hinge on the new testing.
“We are disappointed that the FDA did not approve our application,” Tuan Ha-Ngoc, Aveo’s chief executive, told analysts. “We continue to believe that tivozanib has been demonstrated to be a safe and effective treatment for kidney cancer. Overall, we think this is a loss for patients who would have been helped by tivozanib.”
Renal cell carcinoma is the most common form of kidney cancer in adults, killing tens of thousands of people every year.
FDA spokeswoman Stephanie Yao declined to respond to the comments made by Aveo executives during Tuesday’s conference call. “Federal law and FDA regulations prohibit the agency from discussing applications that have not been approved or may be pending review,” she said.
Ha-Ngoc said the company was not surprised by the FDA decision following last month’s 13-1 advisory committee vote recommending the FDA reject the kidney cancer drug application.
Aveo’s chief medical officer, William Slichenmyer, said the company’s late-stage clinical trial with 517 patients demonstrated the drug slowed progression of the disease, the FDA’s primary “endpoint” standard for assessing a drug candidate. But in a comparison with an existing medicine, Nexavar, tivozanib fell short of showing it improved patients’ “overall survival” — the agency’s secondary criterion — better than Nexavar.
Slichenmyer, however, said that was because Aveo, out of humanitarian concerns, permitted patients who were given Nexavar during the trial to switch to tivozanib when their conditions worsened in what was termed “a one-way crossover.” While stopping short of criticizing the FDA, he suggested that should have been taken into consideration.
“We believe the results were confused because some of the patients . . . received two drugs rather than one,” Slichenmyer told the analysts.
Brian Klein, vice president and senior biotechnology analyst for investment research firm Stifel, Nicolaus & Co. in New York, faulted the company for “poor trial design.”
In the conference call, “they were trying to make the best of a bad situation,” Klein said. “They were extremely defensive about their interactions with the FDA and their perceptions of what the FDA wanted. That does not reflect well on management. It seems from what we all knew that the FDA had signaled they had concerns even before Aveo filed its drug application.”
Klein said “the drug has demonstrated a signal of activity in several oncology indications. It seems to impact the disease and the rate of growth in cancer cells. But the late-stage clinical trial was not appropriately designed” to provide data the FDA would find convincing, he said.
Aveo executives reiterated their plans to move forward, along with their Japanese partner, Astellas Pharma Inc., with testing of tivozanib as a treatment for breast and colorectal cancers. Aveo will fund clinical trials for new drug candidates partly through the $190 million in savings it will generate by laying off 140 employees last week. The job cuts followed the company’s decision to halt its efforts to win approval of tivozanib to treat renal cell carcinoma.