Bristol-Myers Squibb announced this morning that Opdivo has flopped in a late-stage study on non-small cell lung cancer, presenting a stunning setback for the star therapy. Its shares $BMY immediately plunged 18%, wiping out billions in market value, while rival Merck $MRK—a runner-up in the checkpoint market—saw its shares soar 10%.
Researchers had recruited a broad population of 541 previously untreated first line patients whose tumors expressed PD-L1 at ≥ 5%, a key biomarker used to identify patients most likely to respond. The Opdivo arm was compared to a group who received their physician’s choice of alternative therapies. But this time, in the first major reversal for Bristol-Myers, the drug failed to deliver a significant improvement in progression-free survival.
The focus now may center on the level of PD-L1 expression used to qualify patients. Last fall, when the FDA expanded its approval of Opdivo to NSCLC patients whose cancer had spread after chemo, FDA cancer czar Richard Pazdur noted:
“While Opdivo showed an overall survival benefit in certain non-small cell lung cancer patients, it appears that higher expression of PD-L1 in a patient’s tumor predicts those most likely to benefit.”
“The missed result likely reflects the fact that BMY pushed the envelope too far in designing its trial,” noted Bernstein’s Tim Anderson. “Specifically, as mentioned in the press release today, they chose a “cut-off value” for PDL1 expression of 5%. This is in-line with what we had been saying (that 5% was the value), whereas the consensus view had been that the cut-off was 10%. By making it 5%, BMY was in essence trying to broaden the patient population where it could claim a benefit (had results been positive, of course), but failed results suggest they likely made it too broad, meaning they enrolled patients with too little PDL1 expression, and this soured the overall analysis. The population MRK studied was narrower.”
— Sally Church (@MaverickNY) August 5, 2016
I/O investment specialist Brad Loncar had this to say:
Bristol’s more aggressive strategy of focusing on a broader population rather than high PD-L1 expressors has worked out for them in later stages of disease, but it looks like that has finally reached its limit. This is a very disappointing result, but I think they deserve credit for trying to help as many patients as possible.
Merck has been lagging far behind Bristol-Myers Squibb in the checkpoint sales race, with
Opdivo OK’d for use without a diagnostic test while Keytruda patients have to be screened. Free of testing patients, Opdivo has raced far ahead on the sales front. But Keytruda—which was tested in patients with a PD-L1 expression of 50%—looks to have the edge now in a key marketplace.
These two pioneering drugs work essentially the same way. They both dismantle a hurdle that cancer cells rely on to escape an attack by the immune system. That has proven to be a game-changer in many types of cancer, where new combinations are now being tested to provide a one-two punch against cancer cells.
Giovanni Caforio, the CEO at Bristol, had this to say:
While we are disappointed CheckMate -026 did not meet its primary endpoint in this broad patient population, we remain committed to improving patient outcomes through our comprehensive development program, including the ongoing Phase 3 CheckMate -227 study exploring the potential of the combination of Opdivo plusYervoy for PD-L1 positive patients, and Opdivo plus Yervoy, or Opdivo plus chemotherapy in PD-L1 negative patients.
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