Bristol-Myers Squibb (NYSE: BMY) this afternoon revealed yet another setback for its cancer immunotherapy nivolumab (Opdivo) in lung cancer, boosting the outlook for rival Merck.
The New York pharma giant said that a regimen of nivolumab (Opdivo) and chemotherapy failed to extend the lives of non-squamous, non-small cell lung cancer patients compared to chemo alone in a Phase 3 study.
Specifically, newly diagnosed, advanced NSCLC patients on nivo-chemo survived for a median of 18.83 months, while patients on chemo alone survived for a median of 15.57 months. The risk of disease worsening or death was just 14 percent less for nivo-chemo patients than those on chemo alone, which wasn’t statistically significant. The results were “not the outcome we had hoped for,” said Fouad Noumani, Bristol’s head of oncology development, in a statement.
The test was a critical part of Bristol’s massive three-part Phase 3 trial, Checkmate-227, which has the fates of three different Bristol drug regimens riding on it. The Checkmate-227 lung cancer trial has studied nivo alone; a combination of nivo and chemo; and a regimen of two Bristol immunotherapies—nivo and ipilimumab (Yervoy). In a different announcement, Bristol did disclose that its nivo-ipi combination fared better than chemo alone in a separate part of the trial, but it didn’t disclose details.
Nonetheless, the failure of the nivo-chemo combination looms large because it puts further distance between nivo and a rival immunotherapy, pembrolizumab (Keytruda), from Merck.
In October 2015, the FDA approved nivolumab and pembrolizumab within days of one another for patients whose NSCLC had spread after chemotherapy. But a year later, pembrolizumab succeeded in a Phase 3 trial in newly diagnosed advanced NSCLC patients and nivolumab failed.
Since then, Merck has blown past Bristol. Pembrolizumab became the first FDA-approved immunotherapy for a portion of newly diagnosed NSCLC patients, and Merck followed with an FDA approval of pembrolizumab plus chemotherapy for a broader group of those patients. (Roche, too, is in the mix, having won FDA approval of an immunotherapy-chemo combination of its own.)
Data disclosed from Merck’s Keynote-189 study last year showed that pembro-chemo cut the risk of disease worsening or death for NSCLC patients in half, compared to chemo alone. The results reinforced pembrolizumab’s advantage over nivolumab in first-line lung cancer and helped establish the pembro-chemo regimen as the standard of care for many patients with the disease. Checkmate-227 offered nivo a chance to match Merck’s drug, but the gap has instead widened. “Based on all the data points that are lining up…there is now plenty of evidence that Merck has tracked ahead,” wrote Evercore ISI analyst Umer Raffat, in a research note.
The emergence of immunotherapy, meanwhile, has helped upend how many patients with lung cancer are treated. It has become a pillar of treatment along with chemotherapy—which for decades was the main option for patients with advanced lung cancer—and targeted therapies, which home in on genetic mutations like ALK and EGFR. Most patients don’t have the mutations necessary for targeted therapy. Immunotherapy has begun over the past few years to make its mark in the large remaining patient pool. Combinations of immunotherapies and chemo are now approved for patients with NSCLC, the most common form of lung cancer, and small-cell lung cancer, a less prevalent, aggressive form of the disease linked to smoking.
Shares of Bristol fell 4 percent in after-hours trading on Wednesday, while Merck shares inched up about 1 percent. Bristol pushed its quarterly earnings call to Thursday morning in light of the news.