To the scientific world, Moderna's cancer vaccine's results proved that a highly personalized, immune-targeting medication can work. To investors, it didn't work well enough.
Details from Moderna's vaccine study showed that, when added to immunotherapy, it reduced the risk of melanoma returning by 42% when compared with immunotherapy alone.
Adil Daud, director of melanoma research at University of California, San Francisco, who worked on the trial, called it "a massive conceptual breakthrough." Scientists have been studying cancer vaccines for decades without success.
Moderna's stock tanked, however, down 19% in the days after the results were prematurely released.
"Investors wanted to see something that was better, something that really pointed to true differentiation," said Evan Seigerman, an analyst with BMO Capital Markets.
The disconnect shows how investors' expectations can outstrip the promise of experimental medicines -- even ones scientists say are significant advances in treatment.
While researchers celebrated the results, Wall Street was concerned that they might not be enough to persuade doctors to use what is expected to be a costly new combination. New cancer drugs are introduced at prices of around $400,000 or more a year and this therapy requires more complex manufacturing than most.
Pharma companies are under pressure to show success with new drugs. Moderna must prove that its mRNA vaccine technology has a future outside of infectious diseases, where sales have been declining for years. Merck, a co-developer of the vaccine, must prove it can make up revenue that will be lost when its blockbuster immunotherapy Keytruda goes off patent in about two years.
One problem scientists and Wall Street are puzzling over is that a different study showed using Keytruda alone before surgery appeared to produce a similar result to the vaccine in certain melanoma patients. Merck, which partially funded that study, said the two trials are in different patient populations and can't be compared.
Still, it raised questions for doctors. The cost is "definitely a consideration," said Beth Buchbinder, a medical oncologist at Dana Farber Cancer Institute. "It is a lot easier to, you know, pull a bag of pembrolizumab off the shelf," she said, referring to Keytruda.
Immunotherapies such as Keytruda and Bristol-Myers Squibb's Opdivo have substantially reduced the number of deaths attributed to melanoma since being approved over a decade ago. Their efficacy has created a high bar for treatments that have followed.
Moderna's results did validate a thesis that a cancer vaccine, when added to Keytruda, could be beneficial for some patients. The question is which and exactly how many patients that will be.
"It's quite an individualized discussion," Lisa Tachiki, oncologist at Fred Hutch Cancer Center, said, with questions ranging from how far a cancer has spread to whether a person can tolerate the side effects of immunotherapy.
It is also too soon to tell how much longer patients will live on the Moderna treatment. That data isn't expected for more than a year.
"Are we actually helping our patients live a little longer? Or are we just delaying something that potentially can still be salvaged with immunotherapy at the time of recurrence," Tachiki said.
Clinicians said the vaccine holds promise, particularly for those with less advanced melanoma who don't qualify for immunotherapy before surgery because their tumors are less visible.
Moderna and Merck are studying its potential beyond melanoma, which has been driving investor enthusiasm. The vaccine is already being studied in cancers like kidney and lung and the companies are considering other tumor types.
The drugmakers chose to start with melanoma because it is highly sensitive to immunotherapies, said Eliav Barr, chief medical officer of Merck. But he said the real question is whether the vaccine is "a melanoma product, or is this one of those new cancer interventions that may have benefit in a diverse set of cancers."
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