Bristol-Myers puts up Opdivo-plus-Yervoy data, adding to combo-therapy mystery

If you’re looking for certainty in immuno-oncology, Bristol-Myers Squibb’s latest trial data won’t help. The drugmaker reported mixed results from a test of its Opdivo-plus-Yervoy combination in kidney cancer, raising questions about its bid for a broader approval—and adding to the mystery of which combos will win out in the hot immunotherapy race.

Calling the data "encouraging," Bristol-Myers said the combination treatment hit its response-rate endpoint—ORR came in at 41.6%, compared with 26.5% for Pfizer’s Sutent—but narrowly missed its goal of proving the pair could stave off cancer growth better than Sutent did.

The patients in this trial hadn’t been treated before, and Bristol-Myers had been aiming for a new first-line approval for the combo. The hit-one-miss-one mix of results doesn’t necessarily preclude that, analysts said, but a statistically significant win in both columns would have made for an easier case.

The head-to-head trial, called CheckMate-214, found a progression-free survival median of 11.56 months among patients taking the Opdivo-Yervoy combo, compared with 8.38 months for Sutent patients. But though the data "favored" the combo, the difference wasn’t statistically significant, the company said in a Tuesday statement. The trial will continue to allow more data to accumulate toward the third endpoint, overall survival, but those results may not be ready for harvesting till 2019.

What happens in the meantime? "[I]t is worth contemplating whether BMS could still get approval of the regimen based on today's data," Bernstein analyst Tim Anderson said in a Tuesday afternoon note. "It is possible, in our view."

Though it would take a progression-free survival win to achieve full approval in first-line kidney cancer, Anderson noted, "overall response rate with a durable response, and a trend in favor of progression-free survival, could be the basis of an accelerated approval if FDA wants to be accommodating."

Other analysts wondered whether the FDA would indeed be accommodating. The agency could instead choose to wait for proof that the Opdivo-Yervoy tandem actually prolongs patients’ lives. According to Leerink analyst Seamus Fernandez, Bristol-Myers said "it would be discussing the results with regulatory authorities; however, given the narrow PFS miss, it remains unclear to us whether the FDA would require OS data for approval."

The good news? Opdivo is already approved to treat kidney cancer in patients who’ve failed after one round of treatment, and that population—which accounted for 15% to 20% of the drug’s $768 million in Q2 sales—is likely to stick with the drug. "We would be surprised if this data significantly impacts current use of Opdivo in patients with RCC who were previously treated, but it does push out potential expansion into the broader first-line setting," Credit Suisse analyst Vamil Divan wrote in a Tuesday note.

The new data add to a cache of results for PD-1/PD-L1 checkpoint inhibitors in combination with two different types of meds, CTLA4 drugs like Yervoy and chemotherapy drugs. So far, the chemo combos—including a pairing with Merck & Co.’s Keytruda—have put up the stronger results; Keytruda’s chemo combo already has a first-line lung cancer approval. But the CTLA4 data are still rolling in, and the jury is far from finished deliberating.

For Opdivo and Yervoy in particular, the new kidney cancer study is just one of several that will be important to their eventual use in combination. The two meds are already approved to treat melanoma together, and BMS is awaiting more data on the pairing in a variety of other cancers, including lung cancer.

The latter may be the biggest market opportunity, but that doesn’t mean other cancer types aren’t important to the Opdivo-Yervoy combination’s prospects. As Evercore ISI analyst Umer Raffat put it, "in my view, this ‘214 readout is a first of series of readouts for the nivo+ipi combo in non-lung setting which may ultimately determine the peak sales as well as role of this combo."