Troubled tivozanib wedded to Opdivo in new kidney cancer trial

Not wanting to allow a $4 million SEC penalty to get them down, Aveo Oncology ($AVEO) is getting right back into the clinic with its multi-failed cancer candidate tivozanib to be used with Bristol’s ($BMY) PD-1 immunotherapy med Opdivo (nivolumab).

The two companies will specifically combine both meds in patients with advanced renal cell carcinoma (RCC), a form of kidney cancer, with Bristol-Myers supplying its blockbuster drug for use in the Phase I/II Aveo-sponsored TiNivo trial.

The early-stage test will be assessed with escalating doses of tivozanib with Opvido, and then be followed by an expansion Phase II cohort at an established combination dose.

The trial will be led by the Institut Gustave Roussy in Paris under the direction of Professor Bernard Escudier, chairman of the Genitourinary Oncology Committee.

This will be a much needed positive R&D update for the biotech, which has been beleaguered by problems from its VEGF inhibitor for years.

First up in its history, the FDA shot down its hoped-for approval in renal cell carcinoma, calling its pivotal data "uninterpretable" and leading the biotech to lay off more than half of its staff. Then, in December 2013, Astellas and Aveo further dashed hopes for the VEGF blocker by revealing that it was unlikely to meet its primary endpoint in a study on colorectal cancer.

Finally, in early 2014, the two shut down a Phase II study on tivozanib in breast cancer when it failed to enroll enough patients, which looked to have closed the book on the drug's last potential indication.

All of this saw Aveo, now known as Aveo Oncology, badly hit, losing Biogen ($BIIB) and then Astellas as research partners before falling into penny-stock territory and being forced to make a series of job cuts.

But the company is, doggedly, still seeking a reprieve for tivozanib, and in December its shares shot up by 27% after it announced a European licensing pact for the drug. It is also continuing with a trial of the drug as a monotherapy. 

Remarkably, however, it got worse when the SEC handed down a $4 million penalty in March of this year. The fine came while seeking to ban three of its former execs from leading any company ever again after allegedly misleading investors on the safety of tivozanib.

The SEC, via a court in Boston, alleges that Aveo deliberately withheld the fact that the FDA had deep concerns about the drug in its public statements in 2012 and 2013, and failed to tell investors that the regulator wanted a second clinical trial to address concerns about the patient death rate during the first study.

The firm never did undertake that second trial and it was left to the FDA--which rejected the drug three years ago--to tell the public about its concerns, promptly sending the firm's stock price down by 31%.

Aveo raised $53 million in a public offering of its stock in January 2013--all while failing to disclose that the FDA staff had explicitly recommended a second study for tivozanib, according to the SEC.

BMS, too, has hit a recent R&D snag with its seemingly all-conquering Opdivo, which already has a license to treat advanced RCC patients in a second-line setting.

The drug was looking to bump itself up the pathway in non-small cell lung cancer, but this month flubbed a key late-stage trial, hampering its chances of a first-line setting in the disease. Both will hope to have better luck with their combined approach to kidney cancer.

“The introduction of immunotherapies has greatly improved outcomes in renal cell carcinoma, and combination therapy is the obvious next step in advancing treatment,” said Professor Escudier.

Dr. Michael Needle, chief medical officer of Aveo, added: “This study has the potential to unlock a more effective, better tolerated new treatment approach in RCC. We appreciate Bristol-Myers Squibb’s support for this study, and we look forward to working with Dr. Escudier and his team to fully understand this potential.”

Aveo ended Q2 with $39.5 million in cash, according to its latest financials posted this month. 

- check out the release

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