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Moderna's Cancer Vaccine Worked. The Data Leaked Early, and Its Stock Fell 17%.

Moderna and Merck's mRNA melanoma vaccine cut recurrence risk 42% in Phase 3. The data leaked two days before ESMO, and Moderna lost $17 billion in a day.

Sheida Mohassesy
5 min read
#moderna#merck#mrna#cancer-vaccine#melanoma#clinical-trials#stock-market
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Moderna and Merck's personalized mRNA cancer vaccine, intismeran autogene, cut the risk of melanoma returning or death by 42% when added to Merck's Keytruda in a 1,137-patient Phase 3 trial, the companies confirmed on Thursday, October 22, hours after the results leaked on social media and two days before their scheduled debut at the ESMO Congress in Madrid. It is the first Phase 3 win for an individualized neoantigen therapy and for any mRNA-based cancer treatment. Moderna's stock closed down more than 17% the same day, erasing more than $17 billion in market value, because Wall Street had priced in something better.

The Numbers Behind the 42%

The INTerpath-001 trial randomized patients with completely resected stage IIB to IV melanoma two to one: intismeran plus Keytruda, or Keytruda plus placebo. After a median follow-up of 24.6 months, the combination cut the risk of recurrence or death by 42%, a hazard ratio of 0.58. At two years, 82.2% of vaccine patients were recurrence-free versus 70.0% on Keytruda alone. The risk of cancer spreading to distant organs, or death, fell 38%, with two-year distant metastasis-free survival of 88.5% versus 80.2%.

The curves tell a story the headline number hides. In the first six months the two arms were indistinguishable, with a hazard ratio of 0.99. After six months, the hazard ratio dropped to 0.42. That lag is baked into the product: each dose is built from the patient's own tumor, encoding up to 34 neoantigens, and the median time from enrollment to first vaccine dose was 64 days. The companies said they manufactured a vaccine for more than 99% of the 757 patients in the combination arm, though 302 of the 1,749 people screened were excluded because their tumor samples were inadequate.

Overall survival is not mature. The hazard ratio of 0.77 trended in the vaccine's favor but did not meet the pre-specified statistical boundary, and follow-up continues.

How the Data Got Out

The results were due on Saturday, October 24, in ESMO's Presidential Symposium, with publication accepted by The New England Journal of Medicine. Instead, Bloomberg reported that details first surfaced on Thursday from unverified accounts on X. One account shared a report credited to Oncology Central describing a 42% reduction in recurrence or death; the link it posted was not live. BioPharma Dive reported that ESMO then released the study details ahead of the meeting, and Merck and Moderna issued the full data in a press release at 2:59 p.m. Eastern.

By the time Professor Georgina Long of the Melanoma Institute Australia stood up in Madrid to present the late-breaking abstract, the market had already rendered its verdict on screenshots. It was a familiar pattern: earlier this month a Chinese memory maker's unverified DRAM claim knocked 5.5% off Korea's Kospi before anyone saw a spec sheet.

Why a Win Cost Moderna $17 Billion

The problem was the bar, not the result. BioPharma Dive reported that Wall Street expected a 40% to 50% relative reduction, and Moderna itself had said 35% would be clinically significant. The smaller Phase 2 trial had shown 44% initially and a 49% reduction (hazard ratio 0.51) at five years. Against that, 42% read as slippage, and Moderna's shares had swelled more than four-fold since the August 19 topline announcement that the trial had succeeded.

Moderna fell as much as 25% intraday on Thursday, Bloomberg reported, and closed down more than 17%, its worst day since August 20, according to Yahoo Finance. Merck slipped too, by around 1% to 3.9% depending on the time of day. On Friday, Moderna lost more than 1% further and closed near $200.

Analysts split along the obvious line. William Blair's Myles Minter said a "sell-the-news reaction is playing out." RBC Capital Markets' Trung Huynh called the results the "low end" of expectations, showing "deterioration" from earlier testing, and wrote that approval seems likely but commercial success is far less certain. TD Cowen's Tyler Van Buren said the data "represent a highly compelling efficacy profile." The split echoes the week Jensen Huang vouched for CoreWeave and its stock fell 12% anyway: when a stock has already priced the good news, the good news is the trigger.

What Oncologists Saw Instead

Doctors treating melanoma read the same numbers differently. Hussein Tawbi of MD Anderson told BioPharma Dive that after many failed trials, "We were resigned to the fact that this was the best we can do for patients." Roughly a third or more of people with late-stage melanoma die or see their cancer return within five years even with Keytruda. Long, the principal investigator, said the results "have the potential to make a foundational shift" in adjuvant treatment.

The price is side effects, mostly the flu-like kind. Treatment-related adverse events hit 95.8% of combination patients versus 90.0% on Keytruda alone, but grade 3 to 5 events were close: 14.2% versus 13.4%. Fever affected 52.2% of vaccine patients, injection-site pain 51.0% and fatigue 38.5%. Patients stopped a study drug because of side effects more often with the vaccine, 14.0% versus 8.7%. Two treatment-related deaths occurred in the combination arm, both attributed to pembrolizumab, and none to intismeran. Janice Mehnert of NYU Langone, a study investigator, said the side effects are likely "something a lot of patients would be willing to take on" for a longer life.

What Happens Next

Merck and Moderna said they are "engaging with regulatory authorities" and gave no filing timeline. The partners are also running intismeran studies in lung, bladder and kidney cancer; Huynh expects interim kidney results late in 2026 or in the first half of 2027. The field's other big bet, BioNTech's personalized vaccine, recently failed a mid-stage colorectal cancer trial, which makes INTerpath-001 the only Phase 3 proof that the approach works.

Whether the vaccine gets approved is now a regulatory question. Whether it was worth four times Moderna's August share price was answered on Thursday, two days before anyone was supposed to know.

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Frequently asked questions

What did the INTerpath-001 melanoma vaccine trial show?

In 1,137 patients with surgically removed stage IIB to IV melanoma, adding Moderna and Merck's personalized mRNA vaccine intismeran autogene to Keytruda cut the risk of recurrence or death by 42% (hazard ratio 0.58) after a median follow-up of 24.6 months. At two years, 82.2% of vaccine patients were recurrence-free versus 70.0% on Keytruda alone.

Why did Moderna stock fall after positive cancer vaccine results?

Investors had expected a 40% to 50% reduction in recurrence risk and the Phase 2 trial had shown 49% at five years, so 42% landed at the low end. Moderna shares had also risen more than four-fold since the August topline announcement. The stock closed down more than 17% on October 22, 2026, erasing more than $17 billion in market value.

How did the Moderna melanoma data leak?

On Thursday, October 22, 2026, screenshots of the results circulated on X from unverified accounts, two days before the scheduled presentation at the ESMO Congress in Madrid. ESMO then released the abstract early and Merck and Moderna published the full numbers that afternoon.

How does intismeran autogene work?

Intismeran autogene (also called mRNA-4157 or V940) is made for each patient. Doctors sequence the patient's tumor and normal DNA, pick up to 34 tumor-specific mutations called neoantigens, and encode them in a synthetic mRNA. Once injected, the body produces those neoantigens and trains T cells to attack cells carrying them.

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