We’ve gotten used to seeing one success after another in the cancer immunotherapy field, so this morning’s news is a bit of a shock: the Bristol-Myers Squibb flagship antibody, Opdivo (nivolumab), seems to have completely missed its endpoints in a trial in non-small cell lung cancer patients. And this was in over 500 patients who had already been selected for PD-L1 expression. That’s an endogenous ligand for the PD-1 receptor (the target of the antibody), so you’d think that these patients were set up for the therapy to show effects. Clearly, that’s not enough by itself.
The stocks of the two companies are undergoing pre-market moves that are rarely seen for these market caps: BMY was down as much as 19% and MRK up as much as 11%, which represents tens of billions of dollars sloshing around. We’ll see what happens during the day – personally, I think it’s a bit early to conclude that since one PD-1 antibody ran into trouble in this indication, the other PD-1 antibody won’t, but whatever. And in the end, the main thing these results tell us is that PD-1 antibodies can’t do it on their own in every indication, so we have to wait for combination data. Both a selloff in BMY and a rise in MRK would seem to be premature.
Update: one problem seems to be that the Opdivo trial may well have set the cutoff for PD-1L expression too low. Merck’s trials for Keytruda in this indication targeted higher-expressing patients only, and there have certainly been indications that expression level can be a critical variable. Bad trial design, then?