mRNA technology was lifted into commercial success during the pandemic, with two major mRNA vaccines, Pfizer’s/BioNTech’s Comirnaty and Moderna’s Spikevax. With that market closing, where does the mRNA pipeline stand? Is oncology the next wave?

By Patricia Van Arnum, Editorial Director, DCAT, pvanarnum@dcat.org

Putting mRNA on the map
Vaccines using mRNA technology came into prominence during the COVID-19 pandemic, with two major mRNA vaccines: Pfizer’s/BioNTech’s Comirnaty, which posted peak sales of $37.8 billion in 2022, and Moderna’s Spikevax, which posted peak sales in 2022 of $18.44 billion. The success of these mRNA vaccines transformed mRNA technology from a promising area of vaccine and therapeutic development to one with great commercial success, which was realized due to the pressing public health need to develop a COVID-19 vaccine.

Pfizer’s/BioNTech’s Comirnaty was granted full US Food and Drug Administration (FDA) approval in August 2021 for people ages 16 and older. Before that, it was the first COVID vaccine to receive FDA Emergency Use Authorization in December 2020. Moderna’s Spikevax gained full FDA approval for people 18 and older in January 2022 and was granted FDA Emergency Use Authorization in December 2020. The original COVID mRNA vaccines from both Pfizer/BioNTech and Moderna protected against the original SARS-CoV-2 virus, the virus that caused COVID-19. Both vaccines have been updated since over time to target new virus variants. The high revenue growth of these mRNA vaccines has also evolved since their peak sales in 2022 due to declining demand for COVID-19 vaccines and the shift from government-funded COVID vaccine programs to US commercial sales in September 2023 following a declaration of the end of the COVID-19 public health emergency in May 2023. On a revenue basis, both Pfizer and Moderna have seen declining sales for their respective COVID vaccines, with Pfizer posting sales for its mRNA vaccine, Comirnaty, of $5.35 billion in 2024, and Moderna posting 2024 product sales, largely from its COVID vaccine, of $3.08 billion.

Shifting US policy on mRNA vaccines
While the success of mRNA vaccines for COVID-19 was a strong marker for mRNA technology, US government support for mRNA vaccine development took a hit earlier this year (August 2025) when the US Department of Health and Human Services (HHS) announced the wind-down of mRNA vaccine-development activities under the Biomedical Advanced Research and Development Authority (BARDA), including the cancellation and de-scoping of various contracts and solicitations. In all, BARDA is terminating funding for 22 mRNA vaccine-development projects worth about $500 million. The move reflects a shift in US government policy toward mRNA vaccines. Operation Warp Speed, a partnership between HHS, including the Centers for Disease Control and Prevention, the National Institutes of Health, and BARDA, and the US Department of Defense, was launched in 2020 to provide US government funding to help accelerate the development of COVID-19 vaccines, with mRNA technology one platform technology supported through US government funding under Operation Warp Speed.

The wind-down from HHS’ BARDA of mRNA vaccine development activities affect a range of programs including:

• Termination of contracts with Emory University and Tiba Biotech.
• De-scoping of mRNA-related work in existing contracts with Luminary Labs, ModeX, and Seqirus.
• Rejection or cancellation of multiple pre-award solicitations, including proposals from Pfizer, Sanofi Pasteur, CSL Seqirus, Gritstone, and others, as part of BARDA’s Rapid Response Partnership Vehicle and VITAL Hub. The Rapid Response Partnership Vehicle is a multi-purpose program designed to support medical countermeasures, such as vaccines, therapeutics, and medical technology products from early-stage development through advanced development, procurement, sustainment, and commercialization, including manufacturing infrastructure development. VITAL Hub is a BARDA Accelerator Network Hub supporting the development and acceleration of next-generation therapeutic and vaccine platforms and technologies to promote health security.
• Restructuring of collaborations with the US Department of Defense–Joint Program Executive Office affecting nucleic acid-based vaccine projects with AAHI, AstraZeneca, HDT Bio, and Moderna/UTMB.

While some final-stage contracts (e.g., Arcturus and Amplitude) will be allowed to run their course to preserve prior taxpayer investment, no new mRNA-based projects will be initiated, reported HHS. HHS has also instructed its partner, Global Health Investment Corporation, which manages BARDA Ventures, to cease all mRNA-based equity investments. In total, this affects 22 projects worth nearly $500 million. Other uses of mRNA technology within the department are not impacted by this announcement, according to HHS.

Advances in mRNA development
Despite the cutback at BARDA, mRNA technology continues to be a promising field in drug and vaccine development in both academia and in the bio/pharmaceutical industry.

The 2025 European Society for Medical Oncology (ESMO) Congress, held earlier this month (October 17-21, 2025) in Berlin, Germany, highlighted the latest research in oncology, including some advances in mRNA technology. One study of particular note was a study by researchers at the University of Texas MD Anderson Cancer Center that showed improved survival rates for cancer patients being treated with immuno-oncology drugs who also had been treated with a mRNA COVID vaccine. The study was led by Steven Lin, M.D., Ph.D. Professor of Radiation Oncology, and Adam Grippin, M.D., Ph.D., Senior Resident in Radiation Oncology, at the University of Texas MD Anderson Cancer Center.

This study included multiple cohorts of several cancer types, which evaluated patients who had received an mRNA vaccine within 100 days of starting immunotherapy treatment. The study included more than 1,000 patients treated between August 2019 and August 2023.

“This study demonstrates that commercially available mRNA COVID vaccines can train patients’ immune systems to eliminate cancer,” said MD Andersen’s Grippin, in an October 19, 2025, press release in commenting on the study. “When combined with immune checkpoint inhibitors, these vaccines produce powerful antitumor immune responses that are associated with massive improvements in survival for patients with cancer.”

The discovery that mRNA vaccines were immune activators came from research conducted by Grippin during his graduate work at the University of Florida in the lab of Elias Sayour, M.D., Ph,D. While developing personalized mRNA-based cancer vaccines for brain tumors, Grippin and Sayour found that mRNA vaccines trained immune systems to eliminate cancer cells, even when the mRNA did not target tumors directly.

This finding led to the hypothesis that other types of mRNA vaccines might have the same effect, and the approval and use of mRNA-based COVID vaccines created an opportunity to test this hypothesis. Lin and Grippin initiated the study to retrospectively evaluate if MD Anderson patients who received mRNA COVID vaccines lived longer than those who did not receive these vaccines. A multi-center, randomized Phase III trial currently is being designed to validate these findings and investigate whether COVID mRNA vaccines should be part of the standard of care for patients receiving immune checkpoint inhibition.

At ESMO, Moderna presented clinical, safety and translational data from a Phase I/II study evaluating its investigational candidate, mRNA-4359, in combination with pembrolizumab in checkpoint inhibitor-resistant/refractory melanoma patients. mRNA-4359 is an early-stage investigational immune-evasion targeted cancer antigen therapy (CAT) that encodes epitopes of two common immune escape pathways, PD-L1 and IDO1, to elicit antigen-specific T cell responses that may directly kill tumor cells and deplete tumor suppressor cells. mRNA-4359 is being evaluated in an ongoing Phase I/II study as a monotherapy and in combination with pembrolizumab in patients with advanced melanoma and non-small cell lung cancer.

mRNA-4359 is one of several investigational oncology candidates being evaluated by Moderna using mRNA technology. Moderna is partnered with Merck & Co. for mRNA-4157 (intismeran autogene), a personalized therapeutic cancer vaccine, which is being evaluated in multiple cancers with pembrolizumab, including in metastatic melanoma. mRNA-4157 is also being evaluated across other cancers, including non-small-cell lung cancer, renal cell carcinoma, bladder cancer, and other solid tumors.