- Moderna and Merck released detailed Phase 3 results Thursday showing their personalized mRNA vaccine, intismeran autogene, cut the risk of melanoma recurrence or death by 42% when added to Keytruda versus Keytruda alone. The combination also cut the risk of distant spread or death by 38% in the trial of roughly 1,100 patients whose tumors were surgically removed.
- Six melanoma specialists told CNBC the results are a clinically meaningful advance that could become a standard of care after surgery, and Memorial Sloan Kettering’s Michael Postow, a trial investigator, told Bloomberg he was “quite impressed” and that the full therapeutic effect may not yet be visible. A further analysis showed a 58% reduction in the risk of recurrence or death after the six-month mark, which one doctor linked to the roughly six weeks needed to custom-manufacture each shot.
- Investors reacted very differently, with Moderna shares falling as much as 25% Thursday after partial data leaked on social media, and Merck shares also fell. RBC’s Trung Huynh said the result landed at the low end of expectations versus the roughly 49% risk reduction in Phase 2, and wrote that “while approval seems likely, commercial success is far less certain.”
- The stakes go beyond melanoma, since Moderna is trying to build a business beyond its Covid vaccine and Merck is preparing for the eventual loss of patent protection on Keytruda. Moderna shares are still up nearly 600% this year on cancer-shot optimism and, even after Thursday’s drop, remain far above where they were before the company announced in August that the shot worked.
What Happened?
Moderna and Merck published detailed Phase 3 data on their individualized cancer vaccine on Thursday, after partial results leaked on social media days before the presentation planned for thousands of oncologists at the European Society for Medical Oncology meeting in Madrid. The shot trains the immune system to hunt residual cancer cells based on the mutations in each patient’s tumor, and it was tested alongside Keytruda in patients after surgery. Inova’s Sekwon Jang called it a potential major breakthrough and said he expects more of his patients to choose the combination if it is approved, while NYU Langone’s Janice Mehnert said it is the first time adding something to immunotherapy has been seen to boost its efficacy. MD Anderson’s Hussein Tawbi also highlighted relatively mild side effects, including injection-site reactions.
Why It Matters?
The gap between doctors and investors comes down to expectations: Wall Street had priced the vaccine as the starting point for a broader oncology franchise, and the limited data suggested its ability to prevent distant spread may not be as robust as expected. Huynh said the data raise “fundamental questions” about the vaccine’s value proposition versus the current gold-standard therapy, which has similar benefits at potentially much lower cost. Washington University’s George Ansstas noted the Phase 3 trial enrolled some patients at lower risk of recurrence than in Phase 2, which makes the data consistent with the earlier study. Commercial scale is the other open question, because each vaccine must be made for an individual patient, and Oxford’s Lennard Lee said the logistics “could make Amazon look simple.”
What’s Next?
Moderna and Merck will present the detailed results, including safety data, at the ESMO conference in Madrid on Saturday, where a broader swath of oncologists will weigh in. Key open questions include whether the combination helps patients live longer, how long the benefit lasts and which patients benefit most. Moderna CEO Stéphane Bancel said the company is finishing a regulatory filing to get the drug fully approved next year. The companies are also under pressure to prove the approach in non-small cell lung, bladder and renal cell cancers, and Merck’s Dean Li cautioned that success in one tumor type does not guarantee others.
