A cancer vaccine developed by Moderna and Merck & Co. has lived up to expectations, meeting the high expectations of industry observers and doctors by slowing the return of advanced melanoma, according to data released before a major medical meeting.
Moderna and Merck reported in August that a combination of Merck’s “intismeran autogene” vaccine and immunotherapy Keytruda outperformed Keytruda alone in a late-stage trial. This study evaluated the two treatment regimens in the “adjuvant” setting after surgical removal of a tumor.
The companies did not disclose details of the trial at the time, only noting that the combination achieved its primary goal during an early, pre-planned verification of data. Nonetheless, the results were hailed by analysts as a “historic moment” and proof that intismeran is set to generate billions of dollars in sales. Moderna’s stock price subsequently increased more than fourfold.
The announcement made the trial’s presentation next Saturday at this year’s European Society of Medical Oncology meeting one of the most anticipated in the biotechnology sector. Prior to this, Wall Street investors expected that the intismeran regimen would be associated with a 40 to 50 percent relative reduction in the risk of disease recurrence or death.
Moderna had previously stated that a 35% reduction would constitute a clinically meaningful result, which in itself was a high bar given that Keytruda alone reached the 43% mark compared to a placebo.
Screenshots of the results were leaked on social media on Thursday, prompting ESMO to immediately release the carefully guarded details of the study ahead of the meeting. According to these results, intismeran achieved its objective, since the combination reduced the relative risk of disease recurrence or death by 42% compared to Keytruda alone after a median duration of 24.6 months.
The results are slightly below the 44% figure initially seen in a smaller and equally closely monitored phase 2 trial. The long-term results of this study were even more thorough, showing that the risk of relapse was almost cut in half after five years of follow-up.
Shares of both companies immediately fell on the news, with Moderna’s stock price falling nearly 25% and Merck’s stock price falling about 1%.
Some analysts immediately came to the defense of both companies. A “news sell-off reaction is occurring,” wrote Myles Minter, an analyst at William Blair. The results “represent a very compelling efficacy profile and significantly exceed the bar set by physicians for a breakthrough data set in adjuvant melanoma,” added Tyler Van Buren, an analyst at TD Cowen.
RBC Capital Markets analyst Trung Huynh, however, noted that the results were at the “low end” of expectations and showed a “deterioration” from what was seen in previous tests.
“Although approval seems likely, commercial success is much less certain,” Huynh wrote.
Investigators interviewed by BioPharma Dive argued that the data represent a possible advance in the management of a persistent type of cancer.
Even with the availability of Keytruda – one of the most effective cancer drugs in history – a third or more of people diagnosed with advanced melanoma will die or have their disease return within five years of treatment. Drugmakers have had a hard time improving these numbers, with “PD-1” inhibitors like Keytruda as well as other drugs.
“We’ve tried really hard. I’ve done clinical trials. None of them have improved over PD-1,” said Hussein Tawbi, a professor of medicine at MD Anderson Cancer Center and an investigator in the Moderna and Merck study. “We were resigned to the fact that this was the best we could do for patients. And now we see we can do better.”
Adding intismeran to Keytruda also reduced the relative risk of cancer spreading to “distant” organs or tissues by 38% compared to Keytruda alone, the researchers found.
Trial participants who received intismeran reported similar rates of side effects, although these recipients had a significantly higher frequency of fever and pain at the injection site. About 7% of people who received intismeran stopped treatment because of an adverse event, compared with 5% of those in the comparison group.
The risk of these side effects is likely “something many patients would be willing to assume” given their chance of living longer, said Janice Mehnert, director of melanoma and cutaneous medical oncology at NYU Langone Health. Mehnert also participated in the study.
The findings are the product of decades of research into vaccines that can train the body’s immune system to better recognize and track cancer cells. Several previous projects failed because they didn’t trigger a strong enough immune response, stimulated the wrong immune cells, or couldn’t overcome tumors’ ability to thwart the body’s defenses. But more recently, developers like Moderna have turned to the mRNA technology popularized by COVID-19 vaccines to offer a new approach.
This strategy is known as “individualized neoantigen therapy.” It involves sequencing a patient’s tumor to find cancer-specific protein indicators, or “neoantigens,” then delivering the mRNA that encodes them into cells. Their presence triggers a response from immune defenders called T cells to hunt down and destroy any cells containing these proteins.
Intismeran teaches the body to spot up to 34 neoantigens. Another developer, BioNTech, offers individualized therapy in colorectal and pancreatic cancer testing.
Moderna and Merck have now shown that this approach can work in treating melanoma. But doctors and investors aren’t yet sure what impact it might have on other types of cancer or early-stage diseases. BioNTech recently reported that its personalized vaccine failed in an interim trial for colorectal cancer.
Merck and Moderna are conducting additional studies in lung, bladder and kidney cancer. Interim results from a mid-stage renal tumor trial could be obtained later this year or in the first half of 2027, RBC analyst Huynh recently wrote in a note to investors.
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