Another one bites the dust: Bristol Myers Squibb pulls 'dangling' accelerated approval for Opdivo in liver cancer
Bristol Myers Squibb has agreed to pull a second-line liver cancer indication for its blockbuster Opdivo as a monotherapy, becoming the second PD-(L)1 indication to bite the dust after the FDA’s oncology adcomm reviewed six “dangling” accelerated approvals in April.
The outside experts voted against two of the six indications discussed at the meeting, including Opdivo as a monotherapy for hepatocellular carcinoma (HCC) patients who have previously been treated with sorafenib, and Merck’s Keytruda as a third-line treatment for stomach cancer. The adcomm voted 5 to 4 not to maintain Opdivo’s indication, after it failed to show clinical benefit in a confirmatory trial.
“We are disappointed by the position the Advisory Committee and the FDA have taken regarding the continued approval of Opdivo monotherapy as a treatment for HCC post-sorafenib,” BMS’ SVP and head of oncology development Jonathan Cheng said in a statement.
“For the past three and a half years, Opdivo monotherapy has been an important option that physicians have relied on to address this need and is currently the most commonly used therapy in the post-sorafenib setting,” he added.
Merck pulled Keytruda’s stomach cancer indication at the beginning of this month, noting: “we respect the FDA’s efforts to continually evaluate accelerated approvals.”
Opdivo won an accelerated approval as a second-line treatment for HCC back in 2017, becoming the first immunotherapy to get OK’d for this indication. Two years later, a confirmatory study didn’t meet statistical significance in its primary endpoint of overall survival. Last March, the drug landed another, separate accelerated approval in combination with Yervoy for the same setting.
SVB Leerink senior research analyst Daina Graybosch predicted back in April the market impact from the two withdrawals would be “inconsequential,” as there’s a “small and shrinking number of patients eligible” for Keytruda as a third-line gastric cancer treatment, and Bristol Myers could shift HCC patients to its Opdivo plus Yervoy combination.
But Thomas Abrams, an associated professor at Harvard Medical School and paid Merck consultant, said during the adcomm that the combo treatment is reserved for fitter patients who failed a tyrosine kinase inhibitor (TKI) in the first line. Patients on the monotherapy have more comorbidities, he said, adding that “they really are two different patient populations.”
When Richard Pazdur, director of the FDA’s Oncology Center of Excellence, pressed Bristol Myers data for the response rate in this population, though, the drugmaker came up short.
“You’re advocating for a new indication, please provide the response rate – not anecdotal information,” Pazdur said.
While Bristol Myers says it has additional trials in the works for the use of Opdivo as a monotherapy and in combination with Yervoy “across different disease settings,” the company said on Friday that it’s also pursuing “new therapeutic approaches” for patients with HCC.