Merck & Co. and Bristol-Myers Squibb have been head-to-head competitors in melanoma ever since their two immuno-oncology treatments, Keytruda and Opdivo, both won their first FDA approvals. Now, Keytruda has posted some new melanoma data that could help it play catch-up with Bristol-Myers' Opdivo.
Keytruda topped placebo at fending off cancer's return after surgery, an interim analysis of the Keynote-054 trial showed. The details of that spread weren't spelled out, though Merck said Keytruda prolonged recurrence-free survival "significantly longer" than placebo did.
“This result demonstrates the meaningful benefit that Keytruda offers for patients with melanoma," Merck SVP Roger Dansey, head of late-stage oncology development, said in a statement.
Merck says it's planning to discuss the data with regulatory authorities, and those talks could lead to a filing this year. Bristol-Myers' Opdivo, however, just won approval for a new use in the same patients—those who've had their tumors removed but remain at high risk of recurrence.
And that approval was built on data pitting Opdivo against an active comparator, rather than placebo. Opdivo topped its fellow Bristol-Myers immunotherapy Yervoy—which works against CTLA-4 rather than PD-1 as Opdivo does—at holding off a recurrence. Yervoy is now the standard of care in that setting, BMS says. It and Opdivo are also approved as a tandem treatment for advanced melanoma.
In that interim analysis of the CheckMate-238 trial, at 18 months of follow-up, 66.5% of Opdivo patients were cancer-free, compared with 52.7% of patients in the Yervoy group. That comparison includes all patients, regardless of BRAF mutation, which Yervoy was designed to target. Moving the therapy into the post-surgery setting could add around $1 billion in potential Opdivo sales, though some of that would come from patients who might otherwise have used Yervoy, Leerink analysts have said.
Of course, at this point, the details of Keytruda's performance in the Keynote-054 trial aren't available. And analysts see Keytruda as a bonafide rival for Opdivo in the post-surgery—or adjuvant—setting, even though the study used placebo as a control.
"[G]iven that it compared Keytruda to placebo, we are not surprised by the positive results," Credit Suisse analyst Vamil Divan wrote in a note to investors. "Bristol-Myers' Opdivo already has FDA approval for use in the adjuvant melanoma setting (based on RFS superiority over Yervoy), but we believe Keynote-054 will ultimately allow for Merck to enter this market as well and compete for share with Bristol-Myers."
Cowen & Co. analysts see Merck on solid footing there, too. According to a new analysis of the prospects for PD-1/L1 drugs, the market in melanoma will be $4.45 billion in 2024, with Bristol-Myers and Merck as the only two meds in that class to boast adjuvant approvals. Cowen expects the two companies to split that market 50-50 by 2021.
The Keynote-054 study will continue as planned to measure Keytruda's performance against other goals, including whether it can prolong patients' lives in addition to holding off the spread of the disease.
Merck is studying Keytruda combos, too. A pairing with Incyte's experimental drug epacadostat turned in promising results from a phase 1/2 study at the European Society for Medical Oncology meeting last fall.