You don’t always get to see a head-to-head showdown like this one: Merck’s Keytruda (pembrolizumab) and Bristol Myers-Squibb’s Opdivo (nivolumab) were both the subject of presentations at the European Society of Medical Oncology conference, reporting on non-small cell lung cancer trials, and there doesn’t seem to be any doubt that Keytruda looked better. Here’s the paper on it in the NEJM, and it’s hard to avoid Adam Feuerstein’s conclusions:
Keytruda and Opdivo are both highly effective and commercially successful drugs which harness a patient’s immune system to kill a growing list of cancer types. Both drugs are even effective in treating patients with lung cancer that no longer responds to prior therapies.
However, in newly diagnosed lung cancer, a commercial market opportunity that could reach $8 billion in sales annually, Merck’s Keytruda works and Bristol’s Opdivo does not.
Why? Because Bristol gambled big by testing Opdivo in a broad population of new lung cancer patients. The bet blew up. Merck played conservative, choosing to target a smaller group of lung cancer patients with a biomarker suggesting Keytruda would be more effective. Merck’s strategy paid off.
Merck’s Phase III was restricted to enrolling patients who were expressing the PD-L1 biomarker in at least 50% of their cells (which still gives you about half of the total number of available NSCLC patients). Response rates were high compared to the standard chemotherapy, and adverse events were lower. From what I can tell, Keytruda not only improved progression-free survival compared to the standard, but also the real-world endpoint of overall survival. The paper has 6-month data, and you would hope and certainly expect the difference to continue to increase as you go further.
Bristol-Myers Squibb, for their part, were reporting the full results of the study that was such bad news for them recently, and the numbers are, if anything, worse than expected. They set a lower cutoff for PD-L1 expression, using their own test whose numbers are hard to compare to Merck’s, and at those levels Opdivo shows no benefit at all compared to the standard chemotherapy regime. At this point, based on the clinical data we have, the differences between the two drugs couldn’t be more stark – and for two antibodies that are probably quite similar, the lessons about what differences can show up in how you run your clinical trials couldn’t be more stark, either. . .