Moderna shares fall 25.2% despite its vaccine cutting melanoma recurrence risk 42%
Key Facts
Phase 3 results showed that adding the personalized intismeran vaccine to KEYTRUDA reduced the risk of recurrence or death by 42% in patients with high-risk melanoma, according to the prespecified primary analysis after a median follow-up of 24.6 months. Merck and Moderna announced the results, which measure the effect of the combination therapy compared with KEYTRUDA alone. The estimated hazard ratio was 0.58, with a 95% confidence interval of 0.45 to 0.75 and a p-value of <0.001. But the improvement in recurrence does not yet settle the treatment’s effect on overall survival, as the data were immature in the interim analysis. In the market, Moderna shares fell 25.2% during the October 22 session to $183.88, their steepest relative one-day decline on record, according to Reuters.
In outcomes measured after two years, 82.2% of patients who received the combination therapy were alive without recurrence, compared with 70.0% in the KEYTRUDA-only group, according to The ASCO Post. The combination therapy also reduced the risk of distant metastasis or death by 38% in the trial analysis. The proportion of patients alive without distant metastasis after two years was 88.5% with the combination, compared with 80.2% with KEYTRUDA alone. These measures show two aspects of the result: control of tumor recurrence and limiting its spread to distant sites. Lead investigator Georgina Long said the study was “the first Phase 3 study to show that a treatment based on a patient’s unique tumor signature can reduce the risk of recurrence or death from cancer.”
The trial included 1,137 adults who underwent surgery to remove stage IIB to IV cutaneous melanoma. The study assigned 757 participants to intismeran plus pembrolizumab, while 380 received pembrolizumab plus placebo, according to The ASCO Post. The treatment combines a vaccine designed around the characteristics of the patient’s tumor with immunotherapy. Interest in the approach dates to results from the Phase 2 KEYNOTE-942 trial, which showed at five-year follow-up a 49% reduction in the risk of recurrence or death and a 59% reduction in the risk of distant metastasis or death compared with KEYTRUDA alone. The current Phase 3 results test the approach on a larger scale, while continued participant follow-up is needed to determine longer-term outcomes.
On safety, treatment-related adverse events of grade 3 to 5 were reported in 14.2% of patients receiving the combination therapy, compared with 13.4% with KEYTRUDA alone, according to Merck data. These percentages refer to treatment-related adverse events and do not represent the rate of all grade 3 or higher adverse events. Despite the clinical results, the October 22 session’s decline wiped about $24 billion from Moderna’s market value, according to Reuters. The drop came after the stock had risen more than 500% during the year through October 21, prompting analysts to describe the move as a sell-the-news reaction after a strong rally. Merck shares closed down about 1.8% in the same session, while some analysts said investors may question how far the technology can be expanded to other types of cancer.
The overall survival result remains unresolved in the interim analysis: the estimated hazard ratio was 0.77, with a 95% confidence interval of 0.45 to 1.31, and there was no statistically significant difference between the groups. The treatment’s effect on survival therefore requires longer follow-up, while the trial continues to track participants’ long-term outcomes. Merck and Moderna said they are in discussions with regulators about the data, and AP reported that the companies are discussing next steps toward an approval application. In the time-based analysis, the risk of recurrence or death was similar between the groups during the first six months, with an HR of 0.99. After completion of the vaccination regimen at month six, a prespecified sensitivity analysis showed a 58% reduction in risk, with an HR of 0.42.