The official Phase 3 data showed a 42% cut in the risk of melanoma recurrence or death, a hazard ratio of 0.58. The curves did not separate for six months, and a key secondary measure fell short of the earlier, smaller trial. Shares closed down 17.6%, off their lows.
Moderna and Merck released the full results of their Phase 3 melanoma vaccine trial at 2:59 p.m. Eastern on Thursday, two days ahead of the scheduled presentation, after the European Society for Medical Oncology said its embargo on the data had been breached and lifted it.
The numbers met the trial's goals. In the INTerpath-001 study of 1,137 patients with resected stage IIB to IV melanoma, adding intismeran autogene to Merck's Keytruda reduced the risk of recurrence or death by 42% compared with Keytruda alone, a hazard ratio of 0.58, at a median follow-up of 24.6 months. The risk of distant metastasis or death fell 38%, a hazard ratio of 0.62. At two years, 82.2% of patients on the combination were alive and recurrence-free, against 70.0% on Keytruda alone.
Overall survival data are not yet mature, the companies said, but show a favorable trend. They are engaging with regulators.
Moderna shares closed at $202.63, down 17.6% from Wednesday's $245.81. At the close, the company had lost about $17.2 billion of market value in a day. The stock was indicated near $197 in premarket trading on Friday.
Inside every published bar
Measured against the thresholds published before the release, 0.58 clears all of them, from the 0.70 ceiling Goldman Sachs had set to Citi's 0.65 line for a clear win. RBC Capital Markets said investors had hoped for 0.50 to 0.59 and called 0.58 "the low end of expectations," the weakest result within that band, since a lower hazard ratio is better. RBC called the data clinically meaningful and likely approvable, and said U.S. approval could come in 2027.
So why the drop? Investors were anchored on the much smaller Phase 2b study, whose long-term results came in at 0.51 on recurrence and 0.411 on distant metastasis. Set beside those, Thursday's 0.62 on metastasis was the clearest letdown. The trials differ in size and length of follow-up, so the comparison is not like for like, but it is the one investors made.
BMO Capital Markets analyst Evan Seigerman said the reaction likely reflects inflated expectations rather than an indictment of the vaccine's efficacy. He also said the results were not enough to drive confidence given those expectations, and noted that neoadjuvant Keytruda has reached similar hazard ratios in earlier trials, which raises questions about the need for the added therapy.
The six-month question
The most important detail for both sides is the shape of the curve. In the first six months, the two arms were indistinguishable, with a hazard ratio of 0.99. After six months, a pre-specified sensitivity analysis showed a hazard ratio of 0.42 for recurrence and 0.50 for distant metastasis.
Bulls can read that as a feature of how an individualized vaccine works: it takes time to manufacture and to train the immune system, so the benefit appears later and then grows. Skeptics can point out that the 0.42 figure comes from a sensitivity analysis, not the primary endpoint, and that a treatment with no effect for half a year has to justify its cost and complexity against standard care.
William Blair analyst Myles Minter flagged a lack of major differences in efficacy across patients with different tumor mutational burdens, a finding that bears on how well the platform might work in other cancers. Investors had been valuing the program across tumor types, not just melanoma.
The price path
The low of the day, $180.80, came before the official release, after an early posting of what appeared to be the data. Shares recovered after the companies published, rising from about $185.50 at 2:45 p.m. to the close, a gain of about 9%. The broader tape was weak as well, with the Invesco QQQ Trust down 2.9%, though biotech indexes fell less than 1%. Merck closed down 1.8% at $147.24.
Even after Thursday, Moderna is up about 587% this year from $29.49.
What to watch
The full presentation at the congress on Saturday at 10:30 a.m. Eastern and Moderna's investor webcast at 1 p.m., which will add the discussant's view and subgroup detail. Monday is the first trading session afterward. Any regulatory filing timeline and the next overall survival update are the longer-term tests.