Moderna's Cancer Vaccine Cut Recurrence Risk 42% — and the Stock Still Fell

Moderna and Merck's experimental cancer vaccine intismeran cut the risk of melanoma returning or patient death by 42% after roughly two years, when combined with Merck's Keytruda versus Keytruda alone. The first Phase 3 data for a cancer vaccine still sent Moderna's stock down as much as 25% on Thursday, closing 17.6% lower. Merck's shares closed 1.7% lower.

The results leaked two days early through a broken embargo, and analysts speculated the haphazard release rattled investors. By Friday afternoon, Moderna was off another 2%, and Merck was down 1.6%. The vaccine simply wasn't as efficacious as some investors had hoped.

What does this change for practitioners? The fight is now about value, not approval odds.

What does the data actually show?

The Phase 3 trial tested intismeran plus Keytruda against Keytruda alone in melanoma patients. The combination reduced the risk of recurrence or death by 42% over about two years. Solid — but the market reaction shows the bar was higher.

RBC Capital Markets analyst Trung Huynh told investors on Thursday: "While approval seems likely, commercial success is far less certain. The data raises fundamental questions about [intismeran's] value proposition relative to standards of care, particularly neoadjuvant immunotherapy, which produces similar efficacy at potentially much less cost."

That's the competitive threat. Neoadjuvant immunotherapy means giving Keytruda and similar drugs before surgery to shrink tumors, rather than after surgery to prevent recurrence.

Is the comparison fair?

A 2023 study found that giving Keytruda to melanoma patients before surgery significantly extended how long they lived until the cancer returned, spread, or killed them, compared to receiving it after surgery. A Phase 3 trial of Bristol Myers Squibb's Yervoy and Opdivo showed a similar result in late-stage melanoma patients treated before surgery.

Both studies, though, involved patients with clinically detectable Stage 3 cancer — that's how doctors knew to treat them before surgery. The intismeran trial was different: patients didn't know their cancer stage until after surgery, according to Daniel Olson, an oncologist at UChicago Medicine, one of the sites for other intismeran studies.

"People are saying, 'What's the value of an mRNA vaccine if you can just give [Keytruda] neoadjuvantly?'" he said. "Well, these patients, you can't."

Jefferies analysts also questioned whether comparing studies with different patient populations is fair. "While we're not sure this is the right comparison, we see signs [intismeran and Keytruda] have a more durable effect," they wrote in a Friday note.

Why durability is the whole story

Intismeran is a therapeutic vaccine. It works by training a patient's immune system to respond to the neoantigens in their tumor and then attack residual cancer cells, according to Jane Healy, Merck's head of oncology early clinical development, who ran the vaccine's Phase 1 study.

That training takes time. Healy believes it explains why there was no difference between the vaccine group and the Keytruda-only group in the first six months of the Phase 3 study.

"It lends to the durability that [Keytruda] is going in and activating the immune system," she said in an interview. "But [intismeran] is training the immune system in what to recognize."

The Phase 2 data backs the durability thesis. The hazard ratio — a key metric for comparing a new treatment against another drug or placebo — was 0.56 after about two years. It held at 0.51 after five years, bucking the usual degradation that happens when experimental therapies move from small Phase 2 trials into larger Phase 3 studies.

"The longer-term data from the Phase 2 — the five years — showing durable responses in these patients out to five years makes me hopeful that this new class of therapies is capable of this durable benefit," Healy said. "I'm hopeful that we're going to finally see that long-term benefit of vaccines that we get in infectious disease playing out in the oncology setting."

Approval looks likely. Whether intismeran becomes a commercial force depends on years of follow-up data proving that vaccine-style lasting protection — familiar from infectious disease — actually transfers to cancer. If it does, custom mRNA treatment could radically change how certain cancer patients are treated.