Aveo Oncology’s kidney cancer drug gets FDA nod, 8 years after stinging rejection

In two pivotal studies years apart, Aveo Oncology’s drug tivozanib did not help kidney cancer patients live longer overall compared to the standard of care. The FDA approved still approved it, the latest development in a long saga that includes several regulatory stumbles.


For a cancer drug to demonstrate that it works, helping patients live longer is a reasonable expectation. Aveo Oncology failed to reach that benchmark in pivotal studies not once, but twice. The first time doomed the company’s lead drug candidate to an FDA rejection. This week, the FDA approved it.

How Aveo finally won FDA approval for its drug, tivozanib, could be viewed as a story of persistence. It also reflects the changes in cancer therapies and how at least one company is finding a new place in the spectrum of kidney cancer care.

The FDA approval announced Wednesday covers use of the Aveo drug in adults with renal cell carcinoma, the most common type of kidney cancer. Those patients must have cancer that has either relapsed or has not responded to two previous treatments, making tivozanib a so-called third-line treatment.

The Aveo drug is a tyrosine kinase inhibitor (TKI), a type of cancer medicine that blocks enzymes. Tivozanib blocks three receptors of vascular endothelial growth factor (VEGF), a protein that helps form the blood vessels that support cancer growth. The FDA has already approved other cancer drugs that work this way.

Aveo first submitted tivozanib for FDA review in 2012 as a potential first-line kidney cancer treatment. In 2013, an FDA advisory committee voted nearly unanimously against recommending approval. Among the concerns reported at the time was the higher rate of death in the patient group treated with the Aveo drug compared to those given the standard of care drug, an inconsistency the FDA later raised in its rejection of tivozanib. The agency recommended that Aveo conduct another clinical trial. The regulatory stumbles cost Aveo its partnership with Astellas Pharma.

Aveo tested its drug in a new Phase 3 study enrolling 350 patients. Like the previous pivotal study, patients were randomly assigned to receive either tivozanib or sorafenib, a cancer drug co-marketed by Bayer and Onyx Pharmaceuticals under the name Nexavar. But this study included patients whose prior treatment included immunotherapy, which in recent years has moved up to become the standard earlier-line of treatment in several types of cancer.

The main goal was to show progression free survival—how long patients live without the cancer worsening. Tivozanib met that mark, showing a median 5.6 months of progression-free survival compared to 3.9 months in the sorafenib group.

The other study goals were to assess overall survival and the objective response rate to the treatment. The objective response rate to the Aveo treatment was 18% compared to 8% in the control group. But on overall survival, tivozanib again fell short of the control arm. Patients treated with the drug lived a median of 16.4 months compared to 19.2 months in the sorafenib arm.

European regulators approved tivozanib in 2017 for treating advanced kidney cancer. But the drug still encountered hurdles on the way to the FDA. In 2019, the agency twice recommended that Aveo refrain from filing an application seeking approval. Both times, the FDA expressed concern about tivozanib’s failure to beat the standard of care in improving overall survival.

Speaking on a conference call on Wednesday, Chief Medical Officer Michael Needle characterized the overall survival results between the tivozanib group and the sorafenib arm as “similar.” Other therapies have also failed to demonstrate overall survival benefit when compared with VEGF-blocking tyrosine kinase inhibitors, he said, adding that these VEGF-blocking drugs “seem to behave similarly as a class on overall survival.”

While Aveo continued its pursuit of FDA approval, the landscape of kidney cancer care changed. Immunotherapies, such as Bristol Myers Squibb’s nivolumab (Opdivo) and Merck’s pembrolizumab (Keytruda) have won additional FDA approvals in recent years as first-line treatments for kidney cancer. Those drugs weren’t even available when Aveo first submitted its drug for FDA review. But immunotherapy doesn’t work for all cases, which means patients need more options. That’s where Aveo sees its drug fitting. Last year, the company resubmitted tivozanib for FDA review—this time as a third-line treatment.

Chief Commercial Officer Michael Ferraresso said that as immunotherapies emerged in earlier lines of kidney cancer care, physicians have needed to adjust their sequence of treatments in cases where the first and second options don’t work. Ferraresso said Aveo has the advantage of being able to show physicians the data from its clinical studies evaluating patients who previously received immunotherapy.

“It’s important that you know how your drug works in sequence with these newer agents, which are now the standard of care in the front line,” he said. “Many of these older agents do not have that type of dataset.”

Ferraresso said an estimated 16,000 new first-line metastatic patients are diagnosed annually. Of those, about 10,000 need third or fourth treatment options, but nearly half of them go untreated. Those patients are the candidates for Aveo’s drug.

Aveo licensed tivozanib from Kyowa Kirin, a Japan-based pharma company. The U.S. biotech holds exclusive rights to develop and commercialize the drug in cancer in all countries outside of Asia and the Middle East. Aveo has tested tivozanib, by itself and in combination with immunotherapies, in both kidney and liver cancers.

The Aveo drug is a once-a day capsule taken with or without food for 21 days, followed by seven days off treatment until the disease progress or the drug reaches unacceptable toxicity. The most common side effects reported in clinical testing were fatigue, hypertension, diarrhea, decreased appetite, nausea, difficulty speaking, hypothyroidism, cough, and stomatitis, which is an inflammation of the mouth and lips. The drug label has no black box warning about side effects.

Tivozanib, which will be marketed under the name Fotivda, will have a wholesale price of $24,150 per 28-day cycle. That price is higher than sorafenib but less expensive than Eisai’s lenvatinib (Lenvima), which earned FDA approval in 2016 for treating kidney cancer. Aveo plans to make its drug available by the end of March.

Photo: HYWARDS, Getty Images