Melanoma was slower to recur in patients receiving Merck and Moderna’s mRNA vaccine with Keytruda, supporting use of the combination in adjuvant treatment. The partners plan to take the data to the FDA.
Merck and Moderna have linked the combination of Keytruda and an investigational personalized mRNA cancer vaccine to improved outcomes in patients with melanoma, positioning the partners to file for regulatory approvals. Moderna’s share price jumped 91% to $120 in premarket trading Wednesday morning following the announcement.
The highly anticipated readout came earlier than expected for RBC Capital Markets. “This is a surprisingly positive development as we were expecting a year-end readout,” the analysts wrote in a note to investors on Wednesday. “The strength of the underlying data must have been compelling to trigger significance at the interim analysis, meaningfully exceeding investor expectations.”
The Phase 3 INTerpath-001 trial tested intismeran autogene, an mRNA-based cancer vaccine also called V940 or mRNA-4157, in combination with Merck’s blockbuster checkpoint inhibitor. Investigators randomized 1,137 patients 2:1 to receive the combination or single-agent Keytruda for approximately one year after having cutaneous melanoma removed surgically.
People taking the combination lived longer without melanoma returning, achieving the trial’s primary endpoint of recurrence-free survival (RFS). The study also hit a secondary endpoint that looked at how long patients lived without metastatic lesions appearing in other parts of the body.
“We see today’s update as a clear positive for shares and Moderna’s fundamental business,” William Blair analysts said in a note to investors. “We are upgrading shares to Outperform from Market Perform given that we believe Moderna has a clear line of sight to revenue diversification from the COVID business (SPIKEVAX and mNEXPSIKE) now.”
The improvements in RFS and distant metastasis–free survival seen at the prespecified interim analysis are clinically meaningful, Merck and Moderna said in Wednesday’s release. The partners have yet to share specific data, choosing instead to hold these back for a future medical meeting. On safety, Merck and Moderna only said that the drugs’ profiles were consistent with earlier studies and that no new signals were seen.
In June, the partners reported no grade 4 or 5 adverse events in their five-year analysis of Phase 2 data. The analysis raised expectations for the Phase 3 readout, with the study linking the combination to a 49% reduction in the risk of recurrence or death and a 59% reduction in the risk of distant metastasis or death.
The Phase 2 data also showed an encouraging trend toward improved overall survival (OS), the partners said at the time. The companies will continue to evaluate OS in the Phase 3 trial, although as Moderna President Stephen Hoge noted on an earnings call in May, it will take time to accrue the level of data collected in the Phase 2. Hoge expressed confidence in the effect on OS, arguing that “RFS really is survival in this case.”
Merck and Moderna plan to use the Phase 3 data to inform talks with regulators about approval filings. The companies held preliminary discussions with regulators in 2024 about seeking approval based on Phase 2 data, only to receive discouraging feedback from the FDA. Now, Merck and Moderna will enter talks with a larger dataset, plus longer-term follow up from the Phase 2 study.
Analysts have tipped intismeran to generate “multi-billion dollar peak sales.” The forecast makes the asset an important drug candidate for Merck and Moderna, which are respectively contending with the anticipated loss of exclusivity on Keytruda and the collapse of COVID-19 vaccine sales.
Exactly how high intismeran sales go will depend on data in other indications. The efficacy of checkpoint inhibitors in bladder cancer provides confidence that intismeran can work in that setting, David Berman, chief development officer at Moderna, said on an earnings call last month. The “big question” is whether intismeran works in indications where checkpoint inhibitors have failed, Berman added.
“Positive results from the INTerpath-001 study in adjuvant melanoma add positive read-through for ongoing studies of intismeran in other cancer types,” William Blair analysts said. “A readout from the Phase 2 study in adjuvant [renal cell carcinoma] is likely the next to come, with data potentially by year-end. We note that this Phase 2 study may be registrational.”
RBC appeared to agree, writing in their Wednesday note that “INTerpath-001 success validates mRNA cancer approach, unlocking potential upside across oncology.”
