Weeks after Keytruda CRL in high-risk TNBC, Merck claims a win after data mature. How soon will it return to FDA?
There’s been much afoot regarding Merck’s attempts to expand its blockbuster Keytruda drug into high-risk, early-stage triple-negative breast cancer so far in 2021.
In early February, well after Merck had submitted its supplemental BLA for the indication, the FDA’s ODAC unanimously rebuked the pharma’s pitch, saying the data were too immature to be conclusive. FDA cancer czar Richard Pazdur took the extraordinary step of admonishing Merck during the meeting, saying the company should not have assumed or hoped for a positive result before the pivotal study read out. A few weeks later, regulators unsurprisingly handed Merck a complete response letter.
Now, though, the study has reached the interim analysis checkpoint. And Merck says it’s a winner.
The KEYNOTE-522 study — the same trial under the microscope in February’s adcomm — met its dual primary endpoint of event-free survival, Merck announced Thursday morning, demonstrating a statistically significant improvement in EFS compared to the control. Its other primary endpoint, pathological complete response, had previously been met.
Roy Baynes“Now that we are seeing the data mature after four years to include a statistically significant improvement in event-free survival, we look forward to working with the FDA and other global authorities,” Roy Baynes, CMO of Merck Research Laboratories, said in a statement.
Merck has been looking to expand Keytruda into this TNBC population as both a pre-operative (with chemo) and post-op (without chemo) treatment. The early data presented at February’s adcomm proved a real sticking point, with even some patient advocates wondering what the rush was all about.
At the time of the last check-in, researchers had seen just 53% of targeted EFS events and 32% of overall survival events.
It’s not yet clear whether or not the new results will change the agency’s mind regarding this indication, given Merck says the EFS data are now good to go. OS is a secondary endpoint in this study, and Merck did not disclose any related information in Thursday’s announcement.
At least one analyst thinks Thursday’s announcement will ultimately set up Merck for a rebound at the FDA. Barclays’ Carter Gould wrote to investors that although there were no quantitative data released, Merck could see a potential approval as early as next year.
“These data should directly address the panel’s recent concern over the lack of mature EFS data, and we would expect Merck to refile based on these data,” Gould wrote. “This shouldn’t be surprising as Merck itself highlighted during the AdCom that the study had 75-95%+ chance of demonstrating a statistically significant benefit based on its modeling assumptions at the time.”
Even though Keytruda has become one of the best-selling drugs on the planet, bringing in almost $3.9 billion in this year’s first quarter, high-risk TNBC has proven a rare stumbling block for Merck. Before the adcomm rebuff, Keytruda had already come up short to Roche’s rival Tecentriq in patients with PD-L1-expressing TNBC that have unresectable and locally recurrent or metastatic tumors. Merck eventually gained the thumbs up here last November.
But Tecentriq previously failed a confirmatory study for the first-line treatment of the PD-L1 group, which may end up putting its accelerated approval in jeopardy. ODAC voted 7 to 2 in April to maintain its OK, however, as part of the FDA’s broader review of accelerated approvals that missed their primary endpoints in the confirmatory follow-ups.
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