Bristol-Myers star Opdivo fails survival test in a matchup with Nexavar aimed at shaking up the big HCC market
Bristol-Myers Squibb has suffered another painful setback in its years-long quest to expand the reach of Opdivo. The pharma giant this morning noted that their Checkmate-459 study comparing Opdivo with Bayer’s Nexavar in frontline cases of hepatocellular carcinoma — the most common form of liver cancer — failed to hit the primary endpoint on overall survival.
This was a significant milestone in Bristol-Myers’ tally of PD-1 catalysts this year. Nexavar (sorafenib) has been the standard of care in frontline HCC for the past decade, though Opdivo has been making headway in second-line HCC cases, where it’s going toe-to-toe with Bayer’s Stivarga (regorafenib) after recent approvals shook up the market.
The OS rate on Opdivo fell well short of statistical significance, with a p value of 0.0752. We’ll have to wait for an upcoming science conference to get the full picture.
Bristol-Myers shares $BMY were down 4.5% ahead of the opening bell Monday as investors reacted to the news that the company is selling Otezla to satisfy regulators ahead of its big Celgene buyout.
Researchers looked for a silver lining in the latest cut of the data onOpdivo, saying “the results showed a clear trend towards improvement in OS for patients treated with Opdivo compared to sorafenib (Nexavar), a current standard of care.”
“We are encouraged by the promising efficacy and safety trends seen with Opdivo in CheckMate-459, especially as HCC is a devastating and difficult-to-treat cancer, for which there have been no significant advances over sorafenib, a standard treatment, in more than a decade,” said Bruno Sangro, head of the liver unit, Clínica Universidad de Navarra, Pamplona, Spain.
But analysts saw the downside clearly. Vamil Divan from CreditSuisse noted: “While the trial showed a trend towards an overall survival benefit, the lack of statistical significance opens the door for competitors such as Merck, Roche and Astra to become the dominant player(s) in this indication with the various combination trials they are currently running.”
Michael Schmidt at SVB Leerink recently noted:
In the US, Opdivo is gaining rapid market share in 2nd line HCC driven by an aggressive marketing effort by BMY and massive free sampling with some off-label use noted in front-line patients which is supported by strong CM-040 results. In Europe, regorafenib is expected to remain the preferred 2nd line agent in the near term, given differences in treatment pattern and preferences.
Bristol-Myers is by no means finished here, with more results expected on their combo with the CTLA-4 Yervoy. That match-up, though, has already failed in small cell lung cancer while investigators have had to deal with a strong pushback from the FDA in their quest to use high tumor mutational burden definitions to define a new approach to identifying lung cancer patients most likely to respond to Opdivo.
Merck, meanwhile, has famously pressed ahead in its successful drive to gain the lead position in the race to command the PD-1 field. Both Keytruda and Opdivo, though, are expected to remain the two dominant drugs in their field for some time.