Aveo inches closer to completing a crucial trial of its main asset tivozanib—almost four years after the FDA turned down the kidney cancer drug.
The biotech said its TIVO-3 trial pitting tivozanib against Bayer/Onyx's rival VEGF inhibitor, Nexavar (sorafenib), in patients with advanced renal cell carcinoma (RCC), has cleared a first safety review and been given a green light to continue towards a crucial futility assessment that will gauge whether it is likely to meet its efficacy targets in mid-2017. Tivozanib is designed to optimize VEGF blockade while minimizing toxic side effects.
The trial's safety monitoring committee (SMC) has recommended that Aveo recruit additional patients to replace dropouts, but the company says this will not delay matters. It is expecting to complete enrollment in July, around a month earlier than forecasted.
If the trial generates positive results—expected in the first quarter of 2018—it will signal the end of a marathon for Aveo, which has been developing tivozanib since it licensed ex-Asian rights to the compound from Japanese pharma company, Kyowa Hakko Kirin, a decade ago.
In 2013, the regulator rejected Aveo's marketing application for tivozanib, describing the TIVO-1 trial filing as "uninterpretable," in part because the design allowed patients to switch from Nexavar to Aveo's drug once their disease had progressed.
It was an embarrassing setback for the company, which reached another level of seriousness when the Securities and Exchange Commission (SEC) investigated claims it had been aware of the FDA's concerns but failed to disclose them to investors ahead of the verdict. Aveo paid $4 million last year to settle those allegations without admitting any wrongdoing.
In 2013, another trial—comparing tivozanib to Roche's antibody-based VEGF blocker Avastin (bevacizumab) on top of standard chemotherapy in colorectal cancer patients—found Aveo's drug was comparable but no better than its comparator, and the study was discontinued. A setback in a breast cancer trial followed the ensuing year and a run of bad form could have made partners anxious. Aveo has lost Biogen and former tivozanib partner Astellas since the FDA rejection.
The company and its long-suffering shareholders desperately need a win with TIVO-3, but there are other upcoming developments that could reward them for doggedly sticking with the program.
Aveo's European licensee for tivozanib, EUSA Pharma, filed the drug with the EMA and responded to a mid-review set of questions in November. As it stands, all seems to be on course with the EU application process. Approval would prompt a $4 million milestone payment with another $2 million due each time five key member states grant reimbursement approval. Aveo ended 2016 with around $31 million in cash.
Meantime, the biotech recently started a trial in RCC combining tivozanib with Bristol-Myers Squibb's immuno-oncology blockbuster Opdivo (nivolumab). Initial results are expected in March.
"Tivozanib is a unique molecule in that its high selectivity for VEGF is designed to reduce off target toxicity, thereby increasing tolerability and its combinability with other agents, such as immunotherapies," said Aveo Chief Medical Officer Michael Needle, M.D., adding: "we look forward to the futility analysis around midyear."