Same or different—that’s a big question rattling around the immuno-oncology field, where PD-1 and PD-L1 checkpoint inhibitors have put up differing results in clinical trials.
The assessment from Sanofi? The PD-1 drugs themselves are essentially equal. It’s the trial designs that make them look different, Joanne Lager, head of oncology development, said in an interview Wednesday.
You’d think Sanofi would say just the opposite; its PD-1 checkpoint inhibitor, cemiplimab, is up for FDA approval later this year, and it’ll be the sixth in the PD-1/L1 class to hit the market. Carving out a niche for a late-to-market med typically involves emphasizing what’s different—ideally superior—to its predecessors.
Still, science is science. “To date we biologically haven’t been able to show a difference between them,” Lager said. Even robust animal models “aren’t really able to distinguish among them.”
“It’s possible that in immuno-oncology, animal models aren’t as good, and the lung cancer studies are maybe unmasking differences among the drugs,” she added. “But that’s less likely to explain the differences in data” than differing trial designs would be.
The French drugmaker is splitting the difference, so to speak. It’s pressing a hypothesis pharma watchers have been debating: The PD-1s might be equivalent, Sanofi says, but they’re likely superior to the PD-L1 drugs that are their head-to-head rivals. “PD-L1 is not the same thing,” Jorge Insuasty, SVP and global head of development, said during a Wednesday press briefing. “I think PD-1 is better.”
It’s also splitting off from its rivals, mostly going after cancer types the other checkpoint players aren’t: cutaneous squamous cell carcinoma (CSCC), for instance, the indication cemiplimab is seeking right now. There are about 700,000 patients in the U.S., and 10% of those would be appropriate for cemiplimab.
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The PD-1/L1 contrast would explain why Roche’s PD-L1 med Tecentriq has delivered lung cancer data not quite up to the bar set by Merck & Co.’s PD-1 drug Keytruda, which Insuasty acknowledged is the therapy to beat in NSCLC, with Bristol-Myers Squibb’s Opdivo next in line. And it’s one reason Sanofi is determined to go after the lung cancer market even though all five of the drugs that beat it to FDA approval are already jockeying for position there.
“I think we have the opportunity to be third,” he said, after Keytruda—he called it “the standard of care in the short term”—and Opdivo. That would put cemiplimab ahead of all three PD-L1s: Tecentriq, AstraZeneca’s Imfinzi, and late-launcher PD-L1 Bavencio, from Pfizer and Merck KGaA. And as he and Lager both emphasized, taking even a small share of a market as big as lung cancer could amount to some significant sales.
Just as other PD-1/L1 makers, though, Sanofi is now most excited about combination therapies as a way to combat resistance to those drugs, whether it’s inherent and up front or acquired during treatment. Its CD38 drug isatuximab, for instance, is targeted for FDA submission as a multiple myeloma monotherapy late this year or early next. The company’s studying that med alongside cemiplmab in the same disease, which other PD-1 drugmakers have yet to crack, and solid tumors as well.
Or its oncolytic virus and cancer vaccine, in phase 1 alongside cemiplumab, and TGF-beta inhibitor, moving into the clinic soon.
That means cemiplimab is perhaps most important to Sanofi in the long term as a base for combos rather than as a standalone treatment. In lung cancer, for instance, to reach the patients who aren’t benefiting from other monotherapies or cocktails, “we need the monotherapy to evaluate the combo,” Lager said.
In fact, Insuasty contends, “Sanofi has the best product for combinations. It may take five years or 10 years. We’re not aiming to rush.”