- Bristol-Myers Squibb on Friday said its checkpoint inhibitor Opdivo failed a key Phase 3 study testing the drug for first-line use in patients with non-small cell lung cancer. Bristol-Myers hoped to prove Opdivo's efficacy in a broad patient population who hadn't yet been treated with other drugs.
- Opdivo missed its primary endpoint of progression-free survival, failing to lengthen the amount of time without symptoms worsening compared to chemotherapy alone. Both Opdivo and Merck's rival drug Keytruda target a protein known as PD-L1, but Bristol-Myers had hoped to prove Opdivo worked in patients who express a much lower level of PD-L1.
- Bristol-Myers stock fell sharply in early trading Friday, while the trial miss buoyed Merck. Sales of Opdivo have outpaced those of Keytruda by a wide margin, but the door could now be open for Keytruda to gain a key advantage in non-small cell lung cancer (NSCLC).
Although Merck's Keytruda beat Opdivo to market in the U.S. by roughly three months (in melanoma), Opdivo has quickly racked up sales and new indications, setting the pace for the checkpoint inhibitor race.
Bristol-Myers has been more aggressive in targeting a broader patient population for Opdivo than Merck has for Keytruda. In the failed trial, known as CheckMate-026, Bristol-Myers tested Opdivo in patients whose tumors expressed levels of PD-L1 higher than 5%.
Merck, by comparison, recently announced Keytruda demonstrated superior progression-free survival and overall survival compared to placebo in NSCLC patients who tumors expressed PD-L1 at more than 50% (as measured by tumor proportion score). This patient population limits Keytruda to roughly 30% of the NSCLC market.
An independent data monitoring committee stopped the Merck study early due to the positive results, and the company indicated it planned to submit the data to regulators. Detailed results are expected to be presented at an upcoming medical meeting.
Both drugs are currently approved for second-line use in advanced NSCLC with progression after other treatments, but Keytruda was approved along with a companion diagnostic to test whether patient tumors expressed PD-L1. Opdivo has no such restriction on its use right now, which has helped it stake its early lead in the market due to the convenience factor.
Evercore ISI analyst Mark Schoenebaum estimates the NSCLC market is worth about $12 billion overall with the first-line setting grabbing about $7 billion of that market.
Schoenebaum wrote in an analysis note Friday that Opdivo's trial failure might be the biggest clinical surprise of his career as an analyst. Opdivo was expected to go from about $3 billion in revenues in 2016 to as much as $9 billion by 2019, but nearly half of those sales were expected to come from the first-line NSCLC setting—its unclear how that will shake out after the failure.
Bristol-Myers called Friday's results "disappointing" but pointed to its ongoing study testing Opdivo in combination with its earlier immunotherapy Yervoy in PD-L1 positive patients and Opdivo plus chemo or Yervoy in PD-L1 negative patients. The company still intends to pursue indications in the first-line setting with their combination therapies.
"We designed our development program in lung cancer to address the unmet need of every lung cancer patient and our scientific approach is a bold one," said Bristol-Myers CEO Giovanni Cafario in a statement.
"We believe that combination therapy may provide an important opportunity to address the needs of every patient with first-line lung cancer," he added.
Yet the trial failure is a major blow for a drug that looked set to carve out a major slice of the cancer immunotherapy market. The door is now open for Merck to jump ahead with a first-line approval in NSCLC and win back some momentum.