Nivolumab (Opdivo) recently became the first immunotherapy ever approved for people with small cell lung cancer (SCLC), a particularly aggressive form of the deadly disease. But the lead given to its developer, Bristol-Myers Squibb, may be short-lived.
Bristol (NYSE: BMY) said today that its immunotherapy nivolumab (Opdivo) failed a Phase 3 study called Checkmate 331. SCLC patients who had failed one treatment were given either chemotherapy or nivolumab, and patients on Bristol’s drug didn’t live longer than those on chemo.
The news comes just two months after Bristol made history. By winning FDA approval of nivolumab in SCLC in August for people who had failed at least two treatments, Bristol brought the first new therapy to the market for people with SCLC in two decades. It also marked the first time immunotherapy, which has begun to change the way several cancers are treated, broke into SCLC, a fast-moving lung cancer that accounts for about 10 to 15 percent of lung cancer cases. About 2 percent of people with SCLC live five years after they are diagnosed, according to the American Cancer Society, and chemotherapy has been the standard of care for years.
Nivolumab, however, was given an “accelerated” approval, on a thinner body of evidence than the agency typically requires. That approval was based on data from an early stage clinical study showing that 13 of 109 SCLC patients (12 percent) who failed two prior treatments responded to nivolumab for a median of 17.9 months. It wasn’t clear from those data whether nivolumab helped SCLC patients live longer, and Bristol had to provide the FDA more data from additional studies to confirm that benefit.
Checkmate-331 is one of the studies meant to do just that, meaning, at least in theory, Bristol’s approval in SCLC could be in peril. The study was “intended to be confirmatory,” wrote Evercore ISI analyst Umer Raffat. “There is no denying that this is a disappointing outcome.”
When asked whether Bristol was concerned its label could be changed in light of the data, spokesperson Priyanka Shah said in an e-mail that the company doesn’t comment on regulatory strategy. Yet recent precedent is in Bristol’s favor. In May 2017, the Roche immunotherapy atezolizumab (Tecentriq) failed a Phase 3 trial in advanced bladder cancer—a year after an accelerated approval based on a mid-stage trial. Nonetheless, the FDA never changed atezolizumab’s label. It is still approved for bladder cancer.
In addition, Checkmate-331 isn’t the only SCLC study Bristol has going. Another trial, Checkmate-451, is testing nivolumab—as well as a combo of nivolumab and another Bristol immunotherapy, ipilimumab (Yervoy)—as a maintenance treatment in SCLC patients who have yet to progress after chemotherapy. Data are expected by the end of the year.
“We believe this could be a new way to investigate the potential durable efficacy of immunotherapy in SCLC patients,” Shah said in the e-mail.
But even if those data are positive, will they be enough to keep Bristol ahead of its rivals? Roche expects to file for FDA approval by the end of 2018 of a regimen combining atezolizumab with chemotherapy in newly diagnosed SCLC patients. And Merck (NYSE: MRK) and AstraZeneca (NYSE: AZN) are testing their respective immunotherapy/chemo combinations in SCLC as well. “Bristol has put itself at a competitive disadvantage by not having a clear first-line trial in SCLC,” Raffat wrote.
When asked why Bristol chose that strategy, Shah wrote that chemotherapy “can provide [an] initial high response” for SCLC. Thus, the “vast majority of patients” could get through the chemo and move on to nivolumab if Checkmate-451 shows the drug can durably keep their cancer at bay, she wrote.
Bristol has already seen its market lead squashed in the much more prevalent non-small cell lung cancer. In October 2015, the FDA approved nivolumab and the Merck immunotherapy pembrolizumab (Keytruda) 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 NSCLC patients, and Merck followed with an FDA approval of pembrolizumab plus chemotherapy in newly diagnosed patients. Bristol has banked on a combo of nivolumab and ipilimumab to bounce back, but has yet to catch up. Barclays analyst Geoff Meacham, for instance, wrote this morning that the nivo-ipi combination is “less commercially attractive” than pembro-chemo, which “should continue to dominate the first-line lung market for the forseeable future.”