Personalised melanoma mRNA vaccine on track for 2026 approval

A personalised mRNA melanoma vaccine cut the two-year risk of cancer recurrence or death when added to standard immunotherapy, and regulators in the US, Europe and the UK are expected to approve it next year. In a late-stage trial of more than 1100 adults, 82 per cent of those who received the bespoke vaccine plus pembrolizumab were alive without recurrence at roughly two years, against 70 per cent of those on pembrolizumab alone.

The trial, run by Moderna with Merck (known as MSD outside the US), recruited adults who had undergone surgery for high-risk melanomas judged likely to recur or spread to distant sites. Two-thirds of participants were randomly assigned to the tailored vaccine on top of pembrolizumab (an immunotherapy that helps the immune system find and destroy cancer cells); the remainder received placebo injections plus the same drug. Both treatments were delivered every three weeks for up to a year. Side effects were similar between the groups.

How does the vaccine work?

Manufacturers sequence a small sample of a person's tumour and compare it with DNA from the individual's healthy blood cells, pinpointing mutations unique to the cancer. The vaccine, built on the same mRNA platform used in covid-19 vaccines, encodes proteins carrying up to 34 of those mutations.

"The jab contains a fingerprint of proteins specifically associated with the cancer," said Rebecca Lee of the University of Manchester. "This helps [immune] T-cells recognise the cancer better, and then pembrolizumab prevents those T-cells from becoming exhausted once they've started attacking the cancer cells."

What do the numbers actually show?

The headline figure combines recurrence and death into a single endpoint. Alan Melcher of the Institute of Cancer Research in London, who was not involved in the trial, cautioned that because a treated cancer must recur before it causes death, the result should be read mainly as evidence of reduced recurrence. Participants have not been followed long enough to establish whether the vaccine improves overall survival; Lee said those data should arrive within a few years.

Independent experts nevertheless expect rapid regulatory action. "I think approval could be quick, and next year sounds reasonable," said Melcher. Lee agreed: "It's highly likely the US and Europe [including the UK] will approve it next year." She called the result "really exciting" and estimated, based on the trial population, that thousands of people in the UK alone could benefit. In the UK, 19,400 melanoma cases are diagnosed annually, and about 25 per cent are classified as high risk.

Who pays the cost?

The vaccine's economics may prove harder than its science. Because each dose must be tailored to and manufactured for an individual patient, the treatment is expected to be very expensive. A January Reuters report suggested a price near $200,000 per treatment. Moderna and Merck did not respond to a request about cost.

"If it was a cheap drug, I'd definitely say it will get approved [for NHS use], but it's going to be expensive," said Lee, flagging the possibility that the vaccine may not be deemed cost-effective for the UK's National Health Service.

What remains unknown?

Melcher stressed that researchers still cannot identify which patients will benefit most. Some participants may carry mutations in their vaccine that fail to stimulate anti-cancer immunity as predicted, or pembrolizumab may work so well that the vaccine adds nothing. "If we can find immune markers in the blood or tumour that predict patient responses, we could use those to determine who to give the jab to," he said.

James Larkin, also at the Institute of Cancer Research, said personalised vaccines could extend to other immunotherapy-treated cancers, including those of the lung, bladder and kidney — though further research is needed to confirm this and to test whether the vaccines could work as standalone treatments. Pending survival data and payer decisions, dermatology teams managing high-risk melanoma should watch the approvals process as much as the trial results.