The real test for Moderna's cancer vaccine isn't about beating Keytruda. It's keeping cancer from coming back in the long term.

By Jaimy Lee

The first Phase 3 data for a cancer vaccine has raised questions about whether a potential new treatment is worth it

Moderna's stock was down slightly Friday, after plunging 17.6% on Thursday.

Moderna and Merck proved their custom cancer vaccine cut the risk of melanoma returning for longer than the cancer drug Keytruda, but it may take several years to understand if a therapeutic vaccine is better at beating the disease than immunotherapies.

The companies on Thursday released the highly anticipated Phase 3 data for intismeran, showing that a combination of the experimental vaccine and Merck's immunotherapy Keytruda reduced the risk of the cancer returning or the patient passing away by 42% after about two years compared to patients only taking Keytruda.

Though a seemingly striking outcome, the vaccine wasn't as efficacious as some investors had hoped. But the real test of intismeran will be how well the vaccine keeps cancer at bay over time. If it's successful, the custom treatment could radically change how certain patients with cancer are treated.

For now, however, the reaction to the data has been mixed. The study's results were unexpectedly released two days early as a result of a broken embargo, sending down the shares of both companies. Moderna's stock (MRNA) plummeted by as much as 25% on Thursday afternoon to close 17.6% lower. Merck's shares (MRK) closed 1.7% lower.

On Friday, Moderna's stock slipped 1.3%, as did Merck's shares.

Analysts speculated that the haphazard way that the Phase 3 results came out may have rattled investors. Investors are also asking broader questions about whether a brand-new technology like intismeran is as game-changing as it's promised to be, especially when compared to neoadjuvant immunotherapy, which is the practice of giving Keytruda and other immunotherapies to patients before they go through surgery to have their tumors removed.

"While approval seems likely, commercial success is far less certain," RBC Capital Markets analyst Trung Huynh told investors on Thursday. "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."

Keytruda is often given to patients after surgery to prevent the return of their cancer, but sometimes it's administered to patients in advance of surgery to shrink the tumor.

A study published in 2023 found that giving Keytruda to patients with melanoma before surgery significantly extended how long they lived until the cancer came back or spread, or until the patient died, compared to those who received it after surgery. A Phase 3 trial of Yervoy and Opdivo, both of which are immunotherapies owned by Bristol Myers Squibb (BMY), had a similar outcome when given to patients with late-stage melanoma before surgery.

Both studies, however, were done in patients with clinically detectable Stage 3 cancer. That's how the doctors knew to administer the treatment before surgery. But the patients enrolled in the intismeran trial didn't know what stage of cancer they had until after they had surgery, according to Daniel Olson, an oncologist in the UChicago Medicine hospital system, which is 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."

Other analysts also questioned whether comparing studies with different patient populations is fair game.

"While we're not sure this is the right comparison, we see signs [intismeran and Keytruda] have a more durable effect," Jefferies analysts wrote in a note on Friday.

That's the big hope for intismeran, which is a therapeutic vaccine. Experts believe that the protective qualities that we associate with vaccines will work in cancer, hopefully creating lasting stretches of time before cancer comes back than what the currently available drugs can offer.

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

She believes that's why there was no difference between the patients who got the vaccine and those who got Keytruda in the first six months of the Phase 3 study. It takes time for the immune system to be trained, and for Healy, that means the benefits of a therapeutic vaccine will come later.

"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."

In the Phase 2 study for the vaccine, the hazard ratio - an important metric for understanding how well a new treatment performs compared to another drug or placebo - was 0.56 after about two years. But the most up-to-date data shows that the hazard ratio didn't degrade much over time, which commonly happens after experimental therapies move from smaller Phase 2 trials into larger Phase 3 studies. It was 0.51 after five years.

"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, later adding: "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."

-Jaimy Lee

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10-23-26 1706ET