By Jaimy Lee

Doctors and patients are excited about the possible breakthrough, but some analysts believe there's too much enthusiasm

Moderna and Merck said an experimental cancer vaccine paired with Keytruda helped prevent the recurrence of melanoma in a Phase 3 trial.

In 2019, a friend noticed a suspicious mole on Angela Evatt's back that turned out to be melanoma, which had spread to her lymph nodes.

Evatt, who was then 43, had surgery to remove the tumor. Her doctor at Georgetown University's Lombardi Comprehensive Cancer Center then suggested she participate in a Phase 2 clinical trial testing Moderna's personalized cancer vaccine in combination with Merck's Keytruda, one of the immunotherapies considered the standard treatment for this type of cancer.

She and her husband mulled it over - neither of them had heard of mRNA technology at that point - and decided to go for it. Evatt started treatment in March 2020, around the same time that the rest of the world was learning about Moderna and its mRNA-based vaccines, and whether they could prevent COVID-19 infections.

"It was somewhat surreal," Evatt said.

The treatment went well, apart from the shots every three weeks that made her feel tired and sluggish - much like the side effects of an mRNA-based COVID shot. Evatt's cancer hasn't returned. And the experimental cancer vaccine that she received is now making waves after the companies announced Wednesday that it had been successful in a Phase 3 trial.

Investors were thrilled and Moderna's stock (MRNA) soared, closing 177% higher on Wednesday. The stock gave up some of those gains on Thursday, falling 23%. Merck's stock (MRK) - along with the shares of four other pharmaceutical companies - closed at a record high amid a sectorwide rally. Despite the excitement, there are still questions about how strong the Phase 3 data will be when it's published in full and whether this type of technology will work in other types of cancer.

"While data is encouraging for [the] broader cancer vaccine space, [questions] remain on translatability of the data outside adjuvant melanoma," Jefferies analyst Akash Tewari told investors on Wednesday.

Reducing the risk of recurrence

The technology is a therapeutic vaccine, meaning it can help prevent recurrence and metastasis, but it can't keep someone from getting melanoma in the first place.

"This is an individual-level based vaccination for somebody's individual tumor," said Michael Christopher, a dermatologist in Tucson, Ariz., who specializes in early detection of skin cancer.

Here's how the technology works: When a patient's tumor is surgically removed, it's sent to a Moderna lab in Massachusetts to be sequenced, and then researchers identify the unique mutated proteins found on the patient's cancer cells. An algorithm selects up to 34 of those mutated proteins, which are called neoantigens, and the researchers produce an mRNA strand made up of those mutations for a vaccine that is administered the same way as Moderna's COVID shot. Keytruda is administered at the same time to help make sure the patient's immune response activates against the leftover cancer cells.

For about a year, the patient undergoes treatment, which is a combination of the therapeutic vaccine, intismeran autogene, and Keytruda, the world's top-selling cancer drug. There is already evidence that Keytruda and other immunotherapies like Bristol Myers Squibb's (BMY) Opdivo lower the risk of relapse, but doctors are eager to have a treatment that can do more to lessen that risk.

"As it gets higher stage, the risk of relapse gets higher," said Michael Atkins, a researcher for the Phase 2 trial and deputy director of the Lombardi cancer center. "What this vaccine does is reduce that risk of relapse significantly."

The Phase 3 study found that the intismeran-Keytruda combo is better for patients than Keytruda alone, and the Phase 2 trial in which Evatt was a participant showed a 49% improvement in the risk of recurrence or death and a 59% reduction in the risk of distant metastasis or death.

As promising as it sounds - and the technology still has to be reviewed by the Food and Drug Administration before it's approved - not all patients will qualify. The tumors have to be a certain size, for example, according to Christopher.

Wall Street's mixed view

If approved in melanoma, the personalized vaccine could bring in $5.4 billion in sales for each company by 2040, according to William Blair analyst Myles Minter, based on a price of $475,000, which is on par with the prices of CAR T-cell therapies, a type of cancer treatment with a similar process that involves removing some of the cancer cells in a patient's body to create a therapy.

That would be a major win for Moderna, which had $1.9 billion in total revenue last year and has struggled to find its place after sales of the COVID vaccine dwindled.

But some analysts believe the announcement was overhyped.

Melanoma has what is called a high tumor mutational burden, or TMB, which means it has many mutations inside the DNA, making it a strong target for this type of treatment. Not all cancers do, and that implies the vaccine's success in melanoma may not translate to other types of cancer it's being tested in, such as renal-cell carcinoma and bladder cancer.

"We agree the win validates the appropriateness of the adjuvant setting for a vaccine," Leerink Partners analyst Daina Graybosch wrote in a note on Thursday. "But we see relatively little biologic read-through to other indications given melanoma, as the most immune-sensitive and highest-TMB tumor, is uniquely suited for a vaccine."

The other reason for some skepticism is that Moderna and Merck haven't yet released any specifics about how the vaccine performed. Instead, they simply said the experimental therapy met the primary and secondary endpoints in the Phase 3 trial, the defined outcome that was being measured. Analysts expect that the full data will be released in October at an important cancer conference in Madrid.

This is how drugmakers often roll out clinical trial updates. In some instances, a preliminary update like the one this week is far more promising than what the actual clinical data show.

"The reception was overly optimistic and creates expectations that we believe will be difficult to meet," Graybosch wrote.

-Jaimy Lee

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08-20-26 1501ET