Confidential data leaked. A major stock sell-off.

Among the chaos around us Modern And MerckWith the latest data on their personalized cancer vaccine, oncologists see something different: an important milestone in melanoma treatment.

The companies released detailed results of a phase 3 trial of their mRNA-based vaccine on Thursday after partial data leaked on social media platforms earlier in the day.

The vaccine, known as Intismeran Autogene, reduced the risk of melanoma recurrence or death by 42% when given with Merck’s immunotherapy Keytruda, compared with Keytruda alone. The combination also reduced the risk of cancer spreading to distant parts of the body or death by 38% compared with immunotherapy alone, according to a study of about 1,100 patients whose tumors were removed through surgery.

The stock market’s reaction contrasted with the assessment of six melanoma specialists, who told CNBC that the results represent a clinically meaningful advance that could eventually become the standard of care for patients undergoing surgery first who did not receive immunotherapy before their surgery.

“This has the potential to be a major breakthrough in melanoma treatment and also in cancer immunotherapy in general, opening the door to better outcomes for patients,” said Dr. Sekwon Jang, a melanoma specialist at Inova Schar Cancer and principal investigator at one of the study’s US sites.

Dr. Janice Mehnert, NYU Langone skin cancer specialist and study researcher, added, “This is the first time we’ve seen that when you add something to immunotherapy, you actually increase the effectiveness of immunotherapy.”

The vaccine is not far away from hitting the market and reaching melanoma patients for the first time. In an interview ahead of the results, Moderna CEO Stéphane Bancel said the company is completing an application to regulators to seek full approval of the drug next year.

“It’s a very, very happy moment for the specialty and for patients,” he said.

Major progress in melanoma

Immunotherapy like Keytruda awakens the immune system to recognize and attack cancer cells. Unlike preventative vaccines that protect against infections that can cause cancer, Moderna and Merck’s treatment acts like a blueprint to train the immune system to recognize and hunt down remaining cancer cells based on the specific mutations in an individual patient’s tumor.

The importance of the Phase 3 data goes beyond delaying a recurrence, doctors said. Treating melanoma can become significantly more difficult if it comes back after surgery and spreads to distant parts of the body, such as the lungs, brain, or liver. Patients with advanced disease may require additional treatments, including immunotherapy, radiation, or further surgery, and these methods cannot be guaranteed to work.

Preventing cancer recurrence could prevent patients from ever having to face the risks and complexities of metastatic disease.

“If we can essentially cure more patients with early-stage melanoma and never have to deal with unresectable metastases – that’s a wonderful advance,” said Dr. Michael Postow, director of the melanoma service at Memorial Sloan Kettering Cancer Center and researcher on the study.

Ideally, patients might be able to undergo surgery in the future and receive the vaccine and Keytruda without the need for further melanoma treatment, Postow told CNBC.

Still, questions remain about whether the combination will ultimately help patients live longer, what the benefits will be over longer periods of time, and which patients will benefit most.

The results also leave open where the personalized vaccine would fit into a changing melanoma treatment landscape, some experts said.

The study tested the vaccine alongside Keytruda after surgery, rather than against immunotherapies given before surgery. This approach is increasingly being used in eligible patients with resectable melanoma in whom the primary tumor can be removed. The data does not show that using the vaccine approach is more or less effective than immunotherapy before surgery.

The medical community will have more clarity after Moderna and Merck present detailed results at the European Society for Medical Oncology conference on Saturday.

Investors were different from doctors

Moderna shares fell as much as 25% on Thursday before regaining some ground after partial data from the trial was leaked on social media. The sell-off came despite the positive results, highlighting the gap between the treatment’s clinical promise and investors’ expectations of its commercial potential. Moderna shares have also risen nearly 600% this year on cancer vaccine optimism, creating more potential for disappointment on Wall Street.

Investors had hoped the vaccine and Keytruda would repeat results from an earlier phase 2 trial that showed a reduction in the risk of recurrence or death by about 49% after five years, RBC Capital Markets analyst Trung Huynh wrote in a note on Thursday. Huynh described the Phase 3 results as clinically meaningful and would likely support regulatory approval, but said the primary efficacy result landed at the low end of investors’ expectations.

But there was a key difference in the trials: The Phase 3 trial included patients with a broader range of risk profiles, including some with a lower risk of recurrence than those enrolled in the earlier Phase 2 trial, Dr. George Ansstas, who heads the melanoma division at Washington University in St. Louis. This may have moderated the results somewhat, as patients considered to be at lower risk are less likely to have a recurrence in the first place.

“It’s actually great data. It’s broadly consistent with what we proved in the phase 2 study,” said Ansstas, who also worked on the phase 2 study.

The combination showed little difference from Keytruda alone in the first six months of treatment, the companies said. However, a separate analysis of Phase 3 data provided a more encouraging signal about the treatment’s effect after the six-month mark. The vaccine and Keytruda reduced the risk of recurrence or death by 58% from that point on compared to Keytruda alone.

The value of 42% comes from the primary analysis, which included patient outcomes throughout the study follow-up period. The median follow-up time at the time of analysis was about two years, so the result reflects the overall treatment effect and not just what happened before or after the six-month mark.

Ansstas said it could take several months to see the benefits of the personalized cancer vaccine because each shot has to be made individually, a process that could take about six weeks, with patients starting Keytruda in the meantime. Even after vaccination begins, the immune system needs time and repeated doses to develop a response against tumors.

This timeline may help explain why the group that received the combination therapy saw even greater benefits after about six months, Ansstas said. Still, the explanation is more of a hypothesis than proof of when the vaccine takes effect.

Dr. Hussein Tawbi, a melanoma expert and study researcher at the University of Texas MD Anderson Cancer Center, also highlighted the vaccine’s relatively mild side effects, including injection site reactions, as positive.

Keytruda and other cancer therapies can cause potentially serious immune-related side effects. Detailed safety results released Saturday should help clarify the tradeoffs of adding the vaccine to immunotherapy.

There is still more work to be done

For Moderna, it’s not just about melanoma. The company is working to build a business beyond its Covid vaccine as Merck prepares for the possible loss of patent protection for Keytruda.

The companies face several hurdles, including selling an individualized therapy that takes several weeks to develop at scale for a patient.

“I think the downside is that it’s very labor intensive and you have to make vaccines for every person. So you can’t just store a million vaccines and then just send them out when someone needs them,” Dr. Adil Daud, a professor of medicine and melanoma oncologist at the University of California, San Francisco, who was the principal investigator of the phase 3 trial. “There’s time and cost, and it’s probably going to cost a lot of money.”

Moderna and Merck did not provide information on the cost of manufacturing the vaccine.

He added that most people who come to the clinic with a tumor that was not surgically removed may stick with taking Keytruda before surgery because “this approach is simpler and does not expose the patient to the delay” of producing the vaccine.

Daud said he expects the vaccine combination to be used primarily in the adjuvant setting after surgery and will not replace established immunotherapies before surgery. For patients who receive immunotherapy before surgery but have little or no response, the vaccine combination could be another option, he said, although this would likely be for a smaller group of patients.

Moderna and Merck still need to validate the approach in other cancer types, including non-small cell lung cancer, bladder cancer and renal cell carcinoma. Success in melanoma does not automatically guarantee that the approach will also work in other tumors.

“I can dream of building a log cabin, but we got some lumberjacks and just felled a tree,” said Dean Li, president of Merck Research Laboratories, in an interview before the results were published. “If you knock down a tree, you won’t get a hut or a village.”

Moderna’s Bancel sees a bright future for the vaccine and believes it can ultimately help “literally thousands and then tens of thousands and then hundreds of thousands of people with different tumors around the world.”