Moderna mRNA Cancer Vaccine Meets Phase 3 Goal, Stock Soars 177%, Biotech Stocks Rally

On August 19, Moderna and Merck announced that their jointly developed individualized mRNA cancer vaccine, Intismeran autogene (mRNA-4157), met the primary endpoint in a pivotal phase 3 clinical trial. The trial, INTerpath-001, enrolled 1,137 patients with high-risk (stage IIB-IV) melanoma who had undergone complete surgical resection. Patients were randomized 2:1 to receive either the vaccine combined with the PD-1 inhibitor Keytruda or Keytruda alone. A pre-specified interim analysis showed that the combination achieved statistically significant and clinically meaningful improvements in recurrence-free survival (RFS) and the key secondary endpoint of distant metastasis-free survival (DMFS). The safety profile was consistent with previous studies, with no new safety signals observed.

Following the announcement, Moderna's stock surged 177% in a single day, adding approximately US$44 billion to its market capitalization, marking the largest single-day gain since the company went public. The positive news also triggered a broad rally in the A-share biotech sector, with many stocks hitting their daily limit, while Hong Kong-listed mRNA vaccine concept stocks also advanced.

In a separate development, on August 28, BioNTech announced the termination of a phase 2 clinical trial (BNT122-01) of its individualized mRNA cancer vaccine, autogene cevumeran, developed in collaboration with Genentech (a Roche subsidiary), for the adjuvant treatment of colorectal cancer.

The exploration of therapeutic cancer vaccines has a history spanning more than a century. In 2010, the vaccine sipuleucel-T (Provenge), used to treat prostate cancer, was approved by the US FDA, becoming the first therapeutic cancer vaccine to be marketed in the United States. As a monotherapy, it extended the overall survival of patients by an average of 4.1 months, but it had limitations including modest efficacy, high pricing, and complex manufacturing processes. In 2011, its developer Dendreon terminated a partnership with GSK and took on production and sales independently, but the company eventually filed for bankruptcy in 2014.

Neoantigens are mutant proteins that arise from DNA replication errors during tumor cell division. They are expressed only in tumor cells and not in normal tissues, allowing the immune system to recognize them as foreign and mount an attack. This technological approach is based on phase 1 clinical results published in Nature in 2017 by two research teams from the United States and Germany, which provided the first clinical evidence that neoantigen cancer vaccines can effectively activate the immune system. In 2021, a long-term clinical case report in Nature Medicine showed that melanoma patients who received the neoantigen vaccine NeoVax had immune responses that lasted up to four years.