- The Food and Drug Administration on Friday approved a combination of Opdivo and Yervoy, two immunotherapies from Bristol Myers Squibb, for a subset of patients with newly diagnosed, advanced non-small cell lung cancer.
- The approval finally gives Bristol entry into one of the most competitive and fast-moving cancer drug markets. Merck & Co. and Roche have already won U.S. approvals of immunotherapy-based combinations for lung cancer, but unlike Bristol Myers' Opdivo and Yervoy pairing, both of those involve chemotherapy.
- While Bristol Myers touts its regimen as chemotherapy-free, it's not clear whether the pharma will be able to compete. Merck's Keytruda, when combined with chemotherapy, has become the standard of care for a majority of lung cancer patients. Bristol Myers' regimen hasn't proven to be superior.
Friday's approval is a notable milestone for Bristol Myers Squibb, which in recent years has been surpassed in lung cancer by Merck and its now dominant immunotherapy Keytruda. Sales of Merck's drug totaled $11.1 billion in 2019, compared to a still sizable $7.2 billion for Opdivo.
Bristol Myers once paced the immunotherapy field, but fell behind due to a series of missteps and clinical trial failures. Those setbacks allowed Merck's Keytruda, in combination with chemo, to emerge as the standard of care for a majority of patients with newly diagnosed non-small cell lung cancer, the most common form of the disease. Roche moved past Bristol Myers too, earning approval for an immunotherapy-chemo regimen of its own.
Bristol Myers has turned to an in-house combination of its two immunotherapies, Opdivo and Yervoy, to try to carve out a niche. The combination is already approved for certain patients with colorectal, skin, kidney, or liver cancers, and the company has gone to great lengths to prove its worth in lung cancer as well.
Its years-long effort has faced numerous hurdles, in part because Bristol Myers focused on patients with a high level of what's known as tumor mutational burden, or TMB, a measure of the number of genetic mutations within their tumors. The marker isn't as established with regulators as another immunotherapy biomarker based on the amount of the protein PD-L1 expressed on tumor cells. Bristol Myers withdrew approval applications in the U.S. and Europe to accumulate more data, and gave up on attempting to win approval in Europe based solely on the results used to win an FDA OK Friday.
"TMB is potentially an important marker, but there's still a lot of work to be done," said Nick Botwood, Bristol's vice president of oncology clinical development, in a recent interview with BioPharma Dive.
Notably, the FDA approval doesn't make mention of TMB at all. Opdivo-Yervoy is approved for patients whose tumors express at least 1% of PD-L1 on their tumors. Patients on the regimen in Bristol Myers pivotal study, called Checkmate-227, lived a median of 17.1 months, compared to 14.9 months for those on chemotherapy — a reduction in relative risk of 21%.
It's unclear whether those results — as well as data divulged last week from a study called Checkmate-9LA that combines Opdivo and Yervoy with chemotherapy — are good enough to help Bristol Myers challenge Merck.
Botwood noted that between Checkmate-9LA and Checkmate-227, Bristol Myers has shown its drugs extend lives regardless of biomarker status. The FDA is currently reviewing the Opdivo, Yervoy and chemotherapy regimen, with a decision expected by Aug. 6.
But after speaking with experts, SVB Leerink analysts weren't convinced. The results weren't much better than Keytruda and chemotherapy, they wrote.
"Moreover, although community doctors are interested in reducing/eliminating chemotherapy, Yervoy is a poor substitute given its toxicity profile," they added in a note to investors. Yervoy is associated with some severe side effects — like inflammation of the liver or digestive tract — that can occur when the immune cells it activates attack healthy tissue.
A further threat could come from Roche, whose drug tiragolumab produced encouraging results in patients with very high levels of PD-L1 when combined with another immunotherapy. Tigrolumab is a new type of immunotherapy that targets the protein TIGIT.
A Bristol Myers spokesperson said the price of Opdivo and Yervoy together "varies based on a number of factors," including cancer type and how long patients are on treatment. But 18 weeks of the regimen for lung cancer — a median of nine Opdivo doses and three Yervoy doses — costs $104,233, the spokesperson said.
Opdivo-Yervoy, meanwhile, was one of three cancer drug approvals from the FDA on Friday. Rubraca, from Clovis Oncology, became the first PARP inhibitor marketed for prostate cancer. And the Deciphera Pharmaceuticals drug Qinlock was cleared for gastrointestinal stromal tumors.
Ned Pagliarulo contributed reporting.