- Bristol-Myers Squibb's chances of challenging Merck & Co. in the market for lung cancer drugs shrank on Wednesday, when the pharma announced mixed clinical results from a sprawling study of its immunotherapy drugs Opdivo and Yervoy.
- While combining the two drugs together helped previously untreated lung cancer patients live longer than those given just chemotherapy, pairing Opdivo with chemo didn't show a clear statistical benefit over chemo alone, according to high-level data from a study known as CheckMate-227.
- That latter comparison is important, as Opdivo's result falls short of the bar set by Merck's rival Keytruda in the first-line treatment of non-small cell lung cancer (NSCLC). Due in large part to Keytruda's clinical successes, Merck has wrested a leading commercial position in immuno-oncology from Bristol-Myers.
Bristol-Myers' one-time argument that comparisons between Opdivo (nivolumab) and Keytruda (pembrolizumab) are akin to debating Coke versus Pepsi looks more tenuous after release of the data from CheckMate-227.
The study, which enrolled more than 2,200 patients and featured a particularly complex design, is Bristol-Myers' primary vehicle for challenging Merck in first-line lung cancer, a key market for the two companies.
In the trial's first part, Bristol-Myers actually reported success. Opdivo plus Yervoy (ipilimumab) extended overall survival compared to chemotherapy alone in patients whose tumors express a biomarker known as PD-L1.
An exploratory look at patients who don't express PD-L1 also showed a benefit on survival, said Bristol-Myers, which plans to submit for approval of the combination.
But in CheckMate-227's second part, Opdivo paired with chemotherapy didn't yield statistically greater survival over chemo.
Median overall survival for those receiving the immunotherapy was just under 19 months, compared to nearly 16 months for those in the chemo arm. Statistically, this translated into a relative risk reduction of 14%.
By contrast, in Merck's Keynote-189 study, Keytruda plus chemo reduced the risk of death over chemo by 51%. That study reinforced Keytruda's earlier approval in first-line lung cancer and helped drive Merck's share of the metastatic lung cancer market to above 60%, according to data from Cowen.
Cross-trial comparisons aren't perfect, as Merck's study only enrolled patients with a type of NSCLC known as nonsquamous. Bristol-Myers' looked at both nonsquamous and squamous types.
In that latter group, Opdivo plus chemo appeared relatively more beneficial, posting a 31% reduction in the risk of death compared to chemo.
But there too, Merck has struck first, winning approval last year for Keytruda as a first-line treatment for squamous NSCLC based on results from the Keynote-407 study, which showed a 36% risk reduction between the Keytruda combo and chemo.
Bristol-Myers said it would present findings from the second part of CheckMate-227 at an upcoming medical meeting, and indicated it would share data from the first section of the study with regulators.
Earlier this year, the pharma withdrew an application it had filed last year for approval of Opdivo in first-line lung cancer based on a slice of data from CheckMate-227. At the time, Bristol-Myers said the FDA wanted to see data from all of part one of the study, which the company now has in hand.
Opdivo is currently approved for use in lung cancer patients whose tumors have begun to grow again after treatment with chemotherapy.
Even with Keytruda's recent gains, Opdivo remains a blockbuster product, earning Bristol-Myers $3.6 billion globally over the first six months of the year. In melanoma, the combination of Opdivo and Yervoy remains standard therapy, accounting for about 30% of Bristol-Myers' Opdivo sales in the U.S. Sales for use in kidney cancer have been strong, too.
The pharma also has other trials ongoing that could help it match Keytruda. One, called CheckMate-9LA, could offer Bristol-Myers another opportunity in first-line lung cancer, with results due next year.
Speaking on a conference call Thursday, Bristol-Myers' executives emphasized an approval of Opdivo plus Yervoy in first-line lung cancer would offer a chemo-sparing alternative, which might appeal to some patients.
Still, Merck's gains in immuno-oncology are clear, and worries over Opdivo's long-term growth were a part of Bristol-Myers' decision-making in its deal to buy Celgene for $74 billion. Bristol-Myers expects Opdivo sales growth this year, but indicated Thursday that 2020 could see increased competitive pressures, particularly in lung cancer.
Shares in Bristol-Myers fell by more than 4% in post-market trading Wednesday, but rose by 2.5% as Thursday trading began.