Data released by the FDA show that Revolution Medicine’s newly approved pancreatic cancer drug underperformed in a large subgroup of patients, but analysts say the biotech still has a clear winner.
A little over a month after Revolution Medicines received an early FDA approval for its RAS inhibitor Rasonque in pancreatic adenocarcinoma, review documents released by the agency showed that a subtype of patients had a lower objective response rate than others. While the biotech’s stock dropped more than 6% last Thursday on the news, analysts largely saw the investor reaction as overblown.
Rasonque reached a 33% objective response rate (ORR) across all KRAS mutations in the Phase 3 RASolute 302 trial, but digging deeper into that figure showed that certain subgroups fared better, as others performed worse. While patients with a G12V mutation, representing 36% of study participants, achieved an ORR of 50%, the drug’s performance in those with G12D mutations, which represented 43% of the trial’s population, led to an ORR of just 24%.
A smaller cohort with G12R mutations was the weakest subgroup with a 7% ORR, lower even than the control group that received chemotherapy. Patients with G12R mutations represent a small portion of the pancreatic cancer population, RevMed said.
Still, analysts expect a record launch for Rasonque. Prior to the newest FDA document release, analysts at Leerink Partners said that “we think this may earn a place as one of the top oncology launches of all time.”
Rasonque’s approval, which arrived months ahead of schedule, was based on overall survival of 13.2 months compared to 6.7 months for patients receiving chemotherapy. At the time, the FDA’s Oncology Center of Excellence director Angelo de Claro said the early approval was the result of “unprecedented results in an area of high unmet need,” in a disease with a five-year survival rate of just 13%. The data received widespread acclaim and greased the wheels for a quick regulatory push, which included a Commissioner’s National Priority Voucher.
Upon release of the subtype data, Leerink analysts were still bullish on RevMed’s ability to hold strong in the KRAS market, calling it “premature to assume” that Rasonque would lose its position in G12D mutation subtypes. They cited robust progression-free survival (PFS) and overall survival (OS) data, as well as RevMed’s ongoing development program with multiple approaches to KRAS mutations across subtypes.
Similarly, Truist Securities analysts called the release “a small crack in the data” that would be unlikely to change RevMed’s market trajectory in the long run.
“While the divergence warrants attention, we see more nuance, than a fundamental challenge to our RevMed PDAC thesis,” Truist analysts wrote to investors on Oct. 8. “We note that in these new data, G12D efficacy remains clinically meaningful across ORR, PFS and OS, and these exploratory analyses were not powered for cross-mutation comparisons.”
The analysts added that Rasonque is already positioned as the new second-line pancreatic adenocarcinoma standard of care with no nearby competitors in the RAS/KRAS space.
Still, even the small gap in RevMed’s data could provide an opening for others developing KRAS-based treatments in pancreatic cancer. In particular, Astellas’ setidegrasib, currently in Phase 3 studies, is designed to specifically target the G12D mutation. Analysts from Jefferies wrote in a Monday note that Rasonque’s weakness there could be a competitive opportunity for Astellas.
