- Merck & Co. looks set to challenge Bristol-Myers Squibb in yet another cancer immunotherapy indication, announcing Monday the U.S. approval of its checkpoint inhibitor Keytruda together with Pfizer's Inlyta for patients with advanced kidney cancer.
- The combination's approval — a first for Keytruda in renal cell carcinoma — adds a powerful competitor to a market that's particularly important for Bristol-Myers, which has ceded ground to Merck in other areas, most notably lung cancer.
- Over the past year, Bristol-Myers' immunotherapies Opdivo and Yervoy have increasingly been used together for frontline treatment of patients with metastatic renal cell carcinoma who are considered to be at higher risk. Data presented in February, however, showed Merck's pairing delivered a greater survival benefit across all risk levels, potentially positioning it as the new combination of choice.
Kidney cancer is the latest proving ground for pairing immunotherapies with other drugs.
While treatments like Keytruda (pembrolizumab) and Opdivo (nivolumab) have proved startlingly effective for a minority of patients — depending on the tumor type — most don't experience a significant benefit. In response, biopharma companies have leaned on combinations, but only with modest success.
Bristol-Myers' combo of Opdivo and Yervoy has been one of those successes, with approvals in metastatic melanoma, certain types of colorectal cancer and, most recently, advanced renal cell carcinoma.
The pairing has also underpinned a good part of Bristol-Myers' commercial success in immuno-oncology. As Keytruda has become the immunotherapy of choice in lung cancer, more of Opdivo's growth has come in melanoma and renal cell carcinoma, according to Bristol-Myers' executives. However, the combination is also hampered by Yervoy's side-effect profile, which includes severe and fatal immune-related adverse reactions like enterocolitis and neuropathy.
Now, Merck has an answer of its own in the kidney cancer, which ranks as the third largest immunotherapy market.
Approval of Keytruda plus Inlyta (axitinib), sold by Pfizer, comes roughly two months ahead of schedule for Merck.
The OK from the Food and Drug Administration is supported by data from a Phase 3 study called KEYNOTE-426, which pitted the combination against Sutent (sunitinib), another Pfizer drug.
Results showed patients given Ketruda plus Inlyta had a 53% lower risk of death than those treated with Sutent. Nearly six in ten combination-treated patients saw their tumors shrink following treatment, compared to a little more than one-third on the monotherapy arm.
Those numbers are greater than what Bristol-Myers posted in its CheckMate-214 study of Opdivo and Yervoy, also tested against Sutent.
Importantly, Keytruda also showed a survival benefit in patients deemed "favorable risk," a group excluded from Opdivo and Yervoy's approval.
Analysts at Cantor Fitzgerald, an investment bank, see that population as most likely to receive Keytruda plus Inlyta initially, but the KEYNOTE-426 results make the combination a potentially compelling choice in poorer risk groups as well.
Bristol-Myers, though, may have a counter still to come. Results are expected in the second half of this year from a study testing Opdivo with Exelixis' Cabometyx (cabozantinib), a tyrosine kinase inhibitor (TKI) which works similarly to Inlyta.
"Certainly, the [KEYNOTE]-426 data look good in terms of hitting endpoints with good hazard ratios and compelling data," Exelixis CEO Mike Morrissey recently said at March conference hosted by Barclays. "But I think it's a bar that can be surpassed based upon what we know [Cabometyx] can do."
Cabometyx is already approved as a monotherapy in first-line renal cell carcinoma, and holds a sizable market share advantage over Inlyta.
If Keytruda and Opdivo drive a similar benefit — a persistent question for the field — than an advantage in the clinic may come down to which tyrosine kinase inhibitor is the better partner.
Inlyta is only approved as monotherapy as a second-line treatment, and data cited on the drug's label show a benefit only on progression-free survival, not overall.