How different are I-O stars from Merck, Roche and Bristol-Myers? Depends who you ask

It’s no secret that most ASCO watchers decided Merck's data on immuno-oncology star Keytruda would cement its position as king of the all-important lung cancer market. Its rivals have a thing or two to say, though—chiefly, that differences between their drugs and Keytruda are small to nonexistent.

Take Dan Chen, VP and global head of cancer immunotherapy development for Roche’s Genentech unit. The way he sees it, PD-1 and PD-L1 therapies "are very similar."

"Are there small differences between" Roche’s Tecentriq, AstraZeneca’s Imfinzi, Bristol-Myers Squibb’s Opdivo and Keytruda? "Maybe, but any differences are likely to be very small," he said, pointing out that "statistically, if they were all the same, you would expect to see variations trial to trial."

Bristol-Myers’ CEO, Giovanni Caforio, went a step further in an interview with CNBC Monday. "When you look at the totality of the data … there is really no difference between these two medicines," he said of Keytruda and Opdivo.

It behooves both of them to think so, given the growing stack of data behind Merck's Keytruda. But Merck? It begs to differ.

"The notion that a priori these things are all created equal—I think we need data to be able to make that statement," Roy Baynes, Merck SVP and head of global clinical development, said in an interview, adding that, "I think it’s a huge stretch to even be trying to make that statement right now."

Investors are keeping as close an eye on these numbers as anyone, and they're going to need to see results from Roche and Bristol-Myers before they buy the idea that either will be able to catch Merck, which has already posted survival benefits in five Keytruda lung cancer trials. While Roche at ASCO touted positive data in squamous lung cancer and Bristol-Myers highlighted Opdivo’s performance in a new biomarker population, investors continued to rally behind Merck as Keytruda’s latest victories overshadowed both.

Chen says that trial design is to blame for the bigger differences in study performance among the three meds. For backup, he pointed to Merck’s monotherapy Keytruda win in the frontline setting and Opdivo’s fateful flop. "There’s a lot of differences in the way these studies are being run," he added.

With that in mind, "I think at the end of the day the more important thing is to look at the totality of the evidence," Chen said, noting that to date, three of three studies of Tecentriq in the first-line lung cancer market "have been positive."

But analysts are picking up clues that seem to belie Chen's position. Over the weekend, upon lifting a partial clinical hold on an Opdivo combo myeloma trial, the FDA "seemed to indicate that it does not view Opdivo and Keytruda as having identical actions," Credit Suisse analyst Vamil Divan wrote in a research note.

Considering that it last year halted trials testing Keytruda pairings in the disease, the move continued "to feed the narrative that perhaps these drugs will not be as interchangeable as once thought," he said.

Meanwhile, market watchers so far haven’t been able to make sense of some of the class’ more puzzling failures, including a miss for Keytruda—which had previously worked where others had failed—in head and neck cancer last summer.

"Up until yesterday, I would have told you that there are at least 2 different indications where Merck worked and others failed ... and perhaps Merck is just executing these trials much better," Evercore ISI analyst Umer Raffat wrote at the time. "However, as of today, there appears to be no consistency in the inconsistency."

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