Leaked confidential data. A major stock sell-off.
But beneath the chaos surrounding Moderna and Merck‘s latest data on their personalized cancer vaccine, oncologists see something else: an important milestone in melanoma treatment.
The companies on Thursday released detailed results from a Phase 3 trial on their mRNA-based shot after partial data leaked on social media platforms earlier that day.
The vaccine, known as intismeran autogene, reduced the risk of melanoma recurrence or death by 42% when given alongside Merck’s immunotherapy Keytruda, compared with Keytruda alone patients. The combination also reduced the risk of cancer spreading to distant parts of the body or death by 38%, compared with just the immunotherapy, according to the trial on roughly 1,100 patients whose tumors were removed by surgery.
The stock market’s reaction contrasted with the assessment of six melanoma specialists, who told CNBC the results represent a clinically meaningful advance that could even become a standard of care for melanoma patients after surgery.
“This has the potential to be a major breakthrough in melanoma treatment and also cancer immunotherapy in general that will open the door to greater outcomes for patients,” said Dr. Sekwon Jang, a melanoma specialist at Inova Schar Cancer and principal investigator at one of the trial’s U.S. sites.
Dr. Janice Mehnert, NYU Langone skin cancer specialist and trial investigator, added that “this is the first time we’re seeing that when you add something to immunotherapy, you actually boost the efficacy of the immunotherapy.”
Major advance in melanoma
An immunotherapy like Keytruda wakes up the immune system to detect and attack cancer cells. Unlike preventative vaccines, which 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 residual cancer cells based on the specific mutations in an individual patient’s tumor.
The significance of the Phase 3 data extends beyond delaying a recurrence, doctors said. Melanoma can become much more difficult to treat when it returns 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 those methods are not guaranteed to work.
Preventing the cancer from returning could spare patients from ever facing the risks and complexities of metastatic disease altogether.
“If we can essentially cure more patients with earlier-stage melanoma and never have to deal with unresectable metastatic disease — that’s a wonderful advance,” said Dr. Michael Postow, chief of the Melanoma Service at Memorial Sloan Kettering Cancer Center and an investigator on the trial.
Ideally, patients in the future may be able to undergo surgery and receive the vaccine and Keytruda without needing further melanoma treatment, Postow told CNBC.
Still, questions remain about whether the combination ultimately helps patients live longer, how durable the benefit is and which patients benefit most. Experts raised questions about treatment decisions for patients who are candidates for immunotherapy before surgery.
The medical community will get more clarity after Moderna and Merck present the detailed results at the European Society for Medical Oncology conference on Saturday.
Investors diverged from doctors
Moderna shares fell as much as 25% Thursday, before regaining some ground, after partial data from the trial leaked on social media. The sell-off came despite the positive results, underscoring the gap between the treatment’s clinical promise and investor expectations for its commercial potential. Moderna shares are also up nearly 600% this year due to the cancer shot optimism, creating more potential for a Wall Street letdown.
Investors had hoped the vaccine and Keytruda would replicate the results of an earlier phase 2 trial, which showed a roughly 49% reduction in the risk of recurrence or death at five years, RBC Capital Markets analyst Trung Huynh wrote in a note Thursday. Huynh described the phase 3 results as clinically meaningful and likely to support regulatory approval, but said the primary efficacy result landed at the low end of investor expectations.
But there was a key difference in the studies: The phase 3 trial included patients with a broader range of risk profiles, including some at lower risk of recurrence than those enrolled in the earlier phase 2 trial, said Dr. George Ansstas, who leads the melanoma department at Washington University in St. Louis.
“It’s great data actually. It’s consistent with what we’ve proven in the phase 2 trial,” Ansstas said.
Another analysis of the phase 3 data offered a more encouraging signal about the treatment’s effect over time. After the six-month mark, the combination was associated with a 58% reduction in the risk of recurrence or death, compared with Keytruda alone.
Ansstas said the benefit of the personalized cancer vaccine may take several months to emerge because each shot must be custom-manufactured, a process that can take roughly six weeks, while patients begin Keytruda in the meantime. After vaccination begins, the immune system also needs time and repeated doses to develop a response against tumors.
That timeline could help explain why the treatment groups’ recurrence-free survival curves diverged more noticeably around six months, Ansstas said. Still, the explanation is a hypothesis rather than proof of when the vaccine’s effect begins.
Dr. Hussein Tawbi, a melanoma expert and trial investigator at the University of Texas MD Anderson Cancer Center, also highlighted the relatively mild side effects associated with the vaccine, including injection-site reactions.
Keytruda and other cancer therapies can cause potentially serious immune-related side effects. Detailed safety results on Saturday should help clarify the trade-offs of adding the vaccine to the immunotherapy regimen.
More work to be done
For Moderna, the stakes extend beyond melanoma. The company is working to build a business beyond its Covid vaccine, while Merck is preparing for the eventual loss of patent protection on Keytruda.
The companies have several hurdles ahead of them, including selling an individualized therapy that takes several weeks to create for a patient at scale.
“I think the downside is that it’s super labor-intensive, and you’re gonna have to make vaccines for each person, and so you can’t just stockpile a million vaccines and then just ship it out when somebody needs it,” said Dr. Adil Daud, co-director of the Melanoma Center at the University of California San Francisco. “There is the time and expense, and it’s probably going to cost like a lot of money.”
He added that most people who walk into the clinic with a tumor that has not been surgically removed may stick to receiving Keytruda before an operation because “that approach is simpler and doesn’t put the patient through the delay” of creating the vaccine.
Moderna and Merck still need to validate the approach in other cancers, including non-small cell lung cancer, bladder cancer and renal cell carcinoma. Success in melanoma does not automatically guarantee that the approach will work in other tumors.
“I can dream of creating a log cabin, but we got some wood chops, and we’ve just knocked down one tree,” Merck Research Laboratories President Dean Li said in an interview ahead of the results. “Knocking one tree does not give you a cabin or a village.”
For now, the vaccine is not far from potentially entering the market for the first time and reaching melanoma patients. In an interview ahead of the results, Moderna CEO Stéphane Bancel said the company is finishing a filing with regulators to get the drug fully approved next year.
“It’s a very, very happy moment for the field, for patients,” he said.
