Moderna mRNA Cancer Vaccine Gets FDA’s Breakthrough Therapy Designation

Moderna's headquarters in Cambridge, Mass., on May 8, 2020. (Maddie Meyer/Getty Images)

The U.S. Food and Drug Administration (FDA) has granted a “breakthrough therapy” designation to Moderna’s personalized mRNA skin cancer vaccine combined with a drug by Merck for treating patients with high-risk melanoma.

The “breakthrough therapy” designation has been granted to Moderna’s mRNA-4157/V940, an investigational personalized mRNA cancer vaccine, in combination with Merck’s anti-PD-1 therapy KEYTRUDA for “the adjuvant treatment of patients with high-risk melanoma following complete resection,” according to a news release on Feb. 22. The designation was based on positive data from the phase 2b trial.

Melanoma is characterized by uncontrolled growth of cells that produce pigment in the body, and is considered to be the most serious form of skin cancer.

mRNA-4157/V940 is a personalized cancer vaccine that is based on the mutational signature of an individual’s tumor. KEYTRUDA works by boosting the ability of the body’s immune system to fight tumor cells.

“mRNA-4157/V940 in combination with KEYTRUDA provided the first demonstration of efficacy for an investigational mRNA cancer treatment in a randomized clinical trial and potentially represents a new frontier in treating melanoma and other cancers,” said Stephen Hoge, M.D., Moderna’s president.

A “breakthrough therapy” designation is only granted when the FDA wants to expedite and review a particular drug that is intended to treat a serious condition, and when there is primary clinical evidence indicating that the drug could be better suitable for treating the condition compared to other therapies “on at least one significant endpoint.”

The two companies intend to initiate a phase 3 study in adjuvant melanoma in 2023 as well as rapidly expand to more tumor types, including non-small cell lung cancer.

Vaccine Trial, Adverse Events

In the phase 2b trial, mRNA-4157/V940 and KEYTRUDA were given to a group of patients over a year. The study found that the combination reduced the risk of cancer death or recurrence by 44 percent when compared to only using KEYTRUDA.

According to Eric Maroyka, senior director, Center on Pharmacy Practice Advancement at the American Society of Health-System Pharmacists (ASHP), the reason Moderna’s mRNA vaccine was used in combination with KEYTRUDA is that advanced and larger tumors prove hard to eradicate when using a vaccine alone.

Dr. Robert Malone, original inventor of mRNA vaccination as a technology, warned that making conclusions on short-term data could be misleading. “You really have to watch for longer-term outcomes” as some of the mRNA vaccines could have toxic nanoparticles, he said.

As to side effects, 14.4 percent of patients receiving mRNA-4157/V940 and KEYTRUDA experienced serious treatment-related adverse events during the phase 2b trial. This number dropped to 10 percent among those who received KEYTRUDA alone.

In the United States, skin cancer is the most common form of cancer, with one in five citizens estimated to develop it in their lifetimes. Around 9,500 individuals are believed to be diagnosed with skin cancer each day. Every hour, more than two people die of skin cancer in the country.

More than a million Americans are estimated to be living with melanoma. The American Cancer Society estimates that around 97,610 new melanoma cases will be diagnosed this year, with 7,990 people expected to die from it.

Dangers of mRNA Vaccines

Studies have shown that mRNA vaccines targeted at the COVID-19 virus have resulted in dangerous side effects.

One study by Retsef Levi, a professor at the Massachusetts Institute of Technology, found that there was a correlation between a 25 percent surge in heart attack emergency calls among young, healthy Israelis in early 2021 and the country’s mRNA vaccination efforts.

“By now, I believe that the cumulative evidence is conclusive and confirms our concern that the mRNA vaccines indeed cause sudden cardiac arrest as a sequel of vaccine-induced myocarditis. And this is potentially only one mechanism by which they cause harm,” he said in a recent video. “At this point in time, all COVID mRNA vaccination programs should stop immediately.

A peer-reviewed study from April 2022 showed that mRNA vaccines “promote sustained synthesis of the SARS-CoV-2 spike protein” and that “the spike protein is neurotoxic, and it impairs DNA repair mechanisms.”