Moderna, Merck Fall on leaked melanoma data

Moderna (MRNA) and Merck shares fell sharply after detailed phase 3 data for their personalized melanoma vaccine intismeran autogene, given with Keytruda, leaked online ahead of a scheduled presentation. Moderna’s stock fell 21% after the release, as the full dataset landed at the low end of investor expectations despite meeting key efficacy endpoints.

The data were due to be presented at the European Society for Medical Oncology Congress 2026 and have been accepted for publication in The New England Journal of Medicine. The early leak, followed by the formal release later that day, appeared to weigh on market sentiment even as the results were characterized as meaningful for patients and positive relative to many Wall Street forecasts.

In the landmark phase 3 INTerpath-001 trial in completely resected stage IIB-IV melanoma, adding intismeran autogene to pembrolizumab (Keytruda) significantly reduced the risk of recurrence or death by 42% compared with pembrolizumab alone, with a hazard ratio of 0.58 and a 95% confidence interval of 0.45 to 0.75 at the primary pre‑specified analysis. The combination also reduced the risk of cancer spreading to distant parts of the body or death by 38% relative to Keytruda alone.

At two years, about 82% of patients who received the personalized vaccine plus Keytruda were alive without their melanoma returning, versus 70% of those treated with Keytruda alone. Overall survival data are not yet mature, although the companies reported a favorable trend.

The treatment regimen involved a six‑month course of intismeran immunization. During the first six months, efficacy for recurrence or death was comparable between the combination and control arms, with a hazard ratio of 0.99 and a 95% confidence interval of 0.66 to 1.49. For distant metastasis or death in that initial period, the hazard ratio was 1.01 with a 95% confidence interval of 0.58 to 1.79.

After completion of the six‑month immunization regimen, a prespecified sensitivity analysis showed a 58% reduction in the risk of recurrence or death for the combination versus Keytruda alone, with a piecewise hazard ratio of 0.42 and a 95% confidence interval of 0.30 to 0.58. In the same post‑six‑month period, the risk of distant metastasis or death was reduced by 50%, with a hazard ratio of 0.50.

A modified intention‑to‑treat analysis that excluded participants who did not receive at least one dose of intismeran or placebo showed reductions of 49% for recurrence or death and 45% for distant metastasis or death, with hazard ratios of 0.51 and 0.55, respectively.

Treatment‑related adverse events occurred in 95.8% of patients receiving intismeran plus Keytruda and in 90.0% of those on Keytruda alone. Grade 3‑5 treatment‑related adverse events were reported in 14.2% of patients in the combination arm and 13.4% in the Keytruda‑only arm, indicating broadly similar rates of higher‑grade toxicity between regimens.

A trial investigator described the added benefit of the vaccine as coming with milder toxicity and side effects such as injection‑site pain compared with other cancer treatments. The companies plan to present the detailed dataset during the ESMO 2026 Presidential Symposium, underscoring the trial’s status as a landmark study in adjuvant melanoma therapy.

Despite the risk reductions in recurrence and distant metastasis and the higher two‑year recurrence‑free survival rate with the combination, investor expectations had been elevated by earlier announcements. The primary recurrence‑free survival result was viewed as landing at the low end of what some market participants had anticipated.

Analysts characterized the observed relative reduction in recurrence or death as clinically meaningful, even as the share price reaction reflected disappointment against high hopes. The divergence between market response and trial outcomes highlights a gap between financial expectations and clinical benchmarks for success in this high‑profile oncology program.