Pharma, R&D

As rivals wait in line, Merck’s Keytruda scores early FDA nod for frontline patients with the most common form of kidney cancer

Merck’s keystone immunotherapy Keytruda is poised to become the key frontline therapy for a common form of kidney cancer, ahead of checkpoint inhibitor rivals who are vying for a piece of the market for previously untreated patients with renal cell carcinoma (RCC).

Topline data released last October showed a combination of Keytruda and Pfizer’s $PFE tyrosine kinase inhibitor (TKI) Inlyta in the KEYNOTE-426 trial improved overall survival, progression-free survival and overall response rates across risk groups, regardless of PD-L1 status, compared to Pfizer’s Sutent in first-line RCC patients. Merck $MRK offered further detail in February, indicating the Keytruda combo significantly improved OS [reducing the risk of death by nearly half (HR 0.53)] as well as PFS (HR 0.69).

The Keytruda combo had been granted priority review by the US health regulator in February, and on Monday the drugmaker said combo had been approved for firstline RCC.

“Bristol-Myers has been gaining share in the 1L RCC market with their Opdivo + Yervoy combo but Merck’s data appears superior given…Opdivo + Yervoy showed an OS benefit (but not a PFS benefit) over Sutent in the CheckMate-214 trial but only in intermediate and high-risk patients and the benefit, in our view, being driven by the responses seen in patients that were PD-L1 positive. Over time, the availability of a generic version of Inlyta (we assume in 2025) could also provide a cost advantage for the Keytruda + Inlyta regimen over Opdivo + Yervoy,” Credit Suisse analyst Vamil Divan wrote in a February note.

Vamil Divan

TKI’s such as Inlyta and Sutent block chemical messengers enzymes called tyrosine kinases, which help send growth signals in cells. Some analysts have suggested that a TKI/IO combo will emerge as the standard of care in first line RCC, and that they anticipate similar results to emerge from the ongoing CheckMate 9ER trial, which is testing a combination of Bristol-Myer’s $BMY Opdivo and Exelixis’ $EXEL TKI Cabometyx versus Sutent in RCC patients.

Meanwhile, Pfizer and Germany’s Merck KGaA are not far behind. The FDA has agreed to a speedy review for their application to market a combination of their checkpoint inhibitor Bavencio and Inlyta in RCC patients — and the agency is expected to make its decision by June. The combo has shown more than 5 months of PFS benefit (13.8 months vs. 8.4 month with Sutent; HR = 0.69), but the trial has, so far, not demonstrated OS improvement.

Yaron Werber

In March, Cowen analysts surveyed RCC experts and found that 64% of polled specialists expected Keytruda + Inlyta to take the leading position in frontline RCC in the next three years. The experts “do not believe that results from CheckMate-9ER could salvage Cabo for a 1L position. We believe CaboNivo needs to show benefits in both survival and safety to be competitive. Hence the future for the drug will be in 2L where Cabo is increasingly expected to be the dominant drug,” Cowen’s Yaron Werber wrote in a note on Sunday.

About 73,820 new cases of kidney cancer will occur in 2019, and roughly 14,770 people will succumb to the disease this year, the American Cancer Society estimates.


Image: Shutterstock


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VP Oncology Biology
Skyhawk Therapeutics Waltham, MA
Associate Director CMC
Elektroki Boston, MA
Director Process Development
Elektroki Boston, MA
Research Scientist - Immunology
Recursion Pharmaceuticals Salt Lake City, UT

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