Merck, Eisai's Keytruda-Lenvima combo rides strong data to FDA nod in kidney cancer—and it's bad news for Pfizer

Keytruda
Merck and Eisai's combination of Keytruda and Lenvima has won FDA approval for newly diagnosed advanced kidney cancer after showing it could reduce the risk of death by 34% over Pfizer's Sutent. (Merck & Co.)

Merck & Co. and Eisai are adding a powerful new weapon in pharma’s fight for supremacy in kidney cancer. While the pair’s fresh FDA nod tips the balance of competition away from rival Bristol Myers Squibb, it may be Pfizer that stands to lose more.

The combination of PD-1 inhibitor Keytruda and tyrosine kinase inhibitor (TKI) Lenvima scored an FDA go-ahead to treat newly diagnosed patients with advanced kidney cancer, Merck and Eisai said Wednesday.

The approval marks the second indication for the Keytruda-Lenvima pairing following an accelerated approval in endometrial cancer back in 2019 that has since been converted into a full approval. It’s the fifth FDA approval for an immunotherapy regimen in front-line kidney cancer, a group that also includes drugs from Bristol Myers, Exelixis, Pfizer and Merck KGaA.

Merck and Eisai won the FDA's latest kidney-cancer blessing based on phase 3 data from the Keynote-581 trial. The study showed the combo slashed the risk of disease progression or death by a whopping 61% over Pfizer’s aging standard-of-care Sutent. In addition, the combo also cut the risk of death by 34% over Sutent.

Keytruda already bears a first-line kidney cancer nod when used alongside Pfizer’s TKI Inlyta. The other approved immunotherapies in the disease setting are Pfizer and Merck KGaA’s PD-L1 inhibitor Bavencio and Inlyta, Bristol Myers’ dual I-O therapy Opdivo and Yervoy, and most recently Opdivo’s pairing with Exelixis’ TKI Cabomeytx.

While the regimens haven’t been tested against each other, the Bavencio-Inlyta pairing seems to have the worst efficacy among the group. At an interim analysis of the phase 3 Javelin Renal 101 trial, Bavencio and Inlyta cut the risk of disease progression or death by 31% against Sutent. At a second interim analysis, the pairing’s benefit in extending patients’ lives was still not clear.

RELATED: Data favor Merck, Eisai's Keytruda-Lenvima as the winner in kidney cancer, but window still open for Bristol Myers: analyst

Meanwhile, the death risk reduction rates against Sutent for the other regimens were comparable, coming in at around 32% to 34% during similar lengths of follow-up. In an investor’s note in February, SVB Leerink analyst Daina Graybosch credited Keytruda and Lenvima for an impressive 71% tumor response rate, including 16% of patients who saw no signs of cancer after treatment.  

Still, two oncology experts Graybosch talked with didn’t believe Keytruda-Lenvima has a clear edge over Bristol Myers’ regimens, especially the first-to-market combo of Opdivo and Yervoy. That treatment has “strong brand value built from stable long-term (four-year) survival outcomes,” she wrote in the note.

Similarly, a genitourinary oncologist with “extensive clinical trial experience with a primary focus on immunotherapy-based regimens” said the Keynote-581 results weren’t practice-changing, RBC Capital Markets analyst Brian Abrahams noted back in March. The expert did acknowledge that the study set a new bar for front-line kidney cancer,

As for the immuno-oncology/TKI inhibitor race, RBC’s oncologist said he prefers the more established Keytruda-Inlyta combo over the newly launched Opdivo-Cabometyx regimen. The expert said he would save the BMS-Exelixis drugs for patients with extensive disease at diagnosis, which represents about 10% of his patients.

RELATED: Bristol Myers, Exelixis snag Opdivo-Cabometyx kidney cancer nod to challenge Merck, Pfizer

The experts' mixed reviews indicate a potential close rivalry between Merck and BMS in what Graybosch estimated is a $4 billion global kidney cancer market for PD-1/L1 inhibitors.

But Pfizer looks to be the sure loser. Moving forward, the New York pharma’s Sutent will be further pressured by I-Os, and its Bavencio data aren’t on par with the competition. What’s more, as Graybosch noted, Merck and Eisai will aggressively market the add-on of Lenvima—which Merck has a financial stake in—over Pfizer’s Inlyta for Keytruda. 

Meanwhile, Merck is also targeting Sutent in early kidney cancer. In patients with clear-cell renal cell carcinoma, Keytruda recently showed its use after surgery slashed the risk of disease returning or death by 32% compared with placebo.