Personalized Melanoma Vaccine Shows Promise in Large Trial, Sparks Investor Jitters
Translated & summarized from Ynet by baba
A new personalized mRNA vaccine for melanoma patients, developed by Moderna and Merck, has shown significant success in a Phase 3 trial, reducing the risk of recurrence or death by 42% when combined with Keytruda. Despite positive clinical results, Moderna's stock fell due to investor expectations. The vaccine trains the immune system to target specific tumor mutations and is expected to be submitted for U.S. approval by 2027, with its availability in Israel pending regulatory processes.
The story in 5 lines · by baba
- Personalized melanoma vaccine reduced recurrence risk by 42% in Phase 3 trial.
- 82.2% of patients on vaccine plus Keytruda were alive and cancer-free after two years.
- Moderna's stock dropped 18% despite successful trial data, due to high investor expectations.
- The mRNA vaccine is custom-made for each patient based on tumor mutations.
- Companies plan to seek U.S. approval for the melanoma vaccine, potentially by 2027.
A personalized mRNA vaccine developed for melanoma patients significantly reduced the risk of disease recurrence after surgery, according to full Phase 3 trial data from Moderna and Merck released Thursday. Two years post-treatment, 82.2% of patients receiving the vaccine alongside the immunotherapy drug Keytruda remained alive and cancer-free, compared to 70% who received Keytruda alone. The combination also lowered the risk of distant metastasis or death by 38%.
The data, initially intended for presentation at the European Society for Medical Oncology (ESMO) conference in Madrid, were leaked to an oncology news site, prompting the companies to release them early. While oncologists reacted positively, investors expressed concern, causing Moderna's stock to drop approximately 18% by Thursday's close. Analysts attributed the decline to inflated expectations rather than flaws in the data, noting the results were less dramatic than those from a smaller Phase 2 trial.
The vaccine, currently named NTISENMRAN AUTOGENE, utilizes mRNA technology but functions differently from a typical vaccine. It is administered to patients whose tumors have been surgically removed, aiming to train the immune system to detect and eliminate residual cancer cells. The process involves sequencing the patient's tumor and healthy cells to identify up to 34 mutations expected to elicit the strongest immune response, with each patient receiving a custom-made vaccine produced over six weeks.
"This is a much more targeted immune boost, directed specifically against that patient's tumor," explained Dr. Michael Postow, Director of Melanoma Service at Memorial Sloan Kettering Cancer Center. The trial involved 1,137 high-risk melanoma patients (Stages IIB-IV), all of whom received Keytruda, a standard post-operative treatment that releases the 'brake' cancer cells use to hide from the immune system. The personalized vaccine is designed to complement Keytruda's action by marking precise targets for attack. Participants received either the vaccine or a placebo, with injections administered every three weeks for up to nine doses.
Statistically, the 42% relative reduction in the risk of recurrence or death is significant, translating to an absolute difference of over 12 percentage points after two years, meaning roughly one additional patient in eight remained melanoma-free in the first two years. A separate analysis showed an even greater risk reduction of 58% after the full vaccination course. The long-term impact on overall survival is still under investigation, though companies reported a "positive trend."
"This is a very statistically significant result. It's not by chance," stated Dr. Hussein Tawbi, a melanoma specialist at MD Anderson Cancer Center. He highlighted that the added benefit comes with moderate toxicity, comparable to previous studies, with side effects including fatigue, chills, and injection site pain. Dr. Postow described the vaccine as unprecedented in both efficacy and mechanism. One patient 59, diagnosed with Stage IIIC melanoma in December 2023, reported being cancer-free over a year after completing treatment, feeling well and monitored.
Moderna's CEO, Stéphane Bancel, indicated the companies are preparing to seek U.S. approval, anticipating a potential launch by 2027. The FDA's process for this novel type of cancer vaccine remains unclear, according to Knudsen, CEO of the Parker Institute. The treatment's price is also unknown. In Israel, the vaccine would require Ministry of Health registration and inclusion in the national health basket to be publicly funded, as Keytruda is. The success of this approach in other cancers, such as lung, bladder, and kidney, is being explored, although a recent mRNA vaccine for head and neck cancer by BioNTech did not meet its survival improvement goal. Dr. Dean Li of Merck likened the current stage of development to having "a few logs" rather than a complete "log cabin."