The potential of mRNA vaccines was established during the COVID-19 pandemic. Now, a new wave of candidates could soon hit the market for cancer, influenza and more.
The arrival of the COVID-19 pandemic heralded an unprecedented period for the pharmaceutical industry, with vaccines progressing from R&D to worldwide rollout in record time and garnering record-breaking profits for developers. The FDA approval of the mRNA vaccines themselves was also a landmark event, acting as a proof of concept and ushering in this new class of treatments.
“COVID-19 accelerated the timelines of the mRNA pipeline, opening the aperture for the companies to start expanding more broadly into other infectious diseases and then to continue to advance the non-infectious disease part of their mRNA pipelines,” said Jennifer Heller, a partner at McKinsey & Company, which recently published a report on innovation in vaccine development.
This is what happened for Moderna, which recently followed its COVID-19 vaccine with the FDA approval of a respiratory syncytial virus (RSV) vaccine.
The global mRNA therapeutics market size is expected to reach $68 billion by 2030, according to Statista. Within the overall vaccine pipeline, Heller told BioSpace that mRNA technology is disproportionately represented when compared to other technologies, particularly in Phase I trials.
One advantage for mRNA developers is that they can rapidly develop a potential product, as happened during the pandemic. This means that the growth in mRNA vaccines at the early stage of the pipeline could soon be seen later on. It could also establish the technology’s advantage over traditional vaccines, which typically take between five and 10 years to develop and bring to the market.
“The advantage of being able to rapidly create a product that can be tested in the clinic lends itself to accelerated development and that’s been the promise of this technology platform,” Heller said. “I think we’re still in early days and so we’ve only had a few products to look at, but I think the trend suggests favorable timelines.”
Here, BioSpace highlights five mRNA vaccine candidates that could reach patients in the near future.
Pfizer/BioNTech’s PF-07252220
Influenza and an influenza/COVID-19 combo
Since successfully developing COVID-19 vaccine Comirnaty, Pfizer and BioNTech have extended their collaboration to build a pipeline of mRNA vaccines. The next likely candidate for approval is an influenza vaccine, PF-07252220, with Pfizer last year releasing Phase III trial results that demonstrated “superiority to a licensed flu vaccine” in participants 18 to 64 years of age.
The partners also plan to move forward with a combination mRNA vaccine against both influenza and COVID-19. However, this move was struck a recent blow when the companies announced that the vaccine met only one of its two primary immunogenicity endpoints. While specific data were not provided, they reported that the combination vaccine had strong efficacy against influenza A but was weaker against the influenza B strain. The companies said they will consider “adjustments” to the candidate, but this is likely to result in delays before any potential approval and the possibility of losing ground to rivals.
Moderna’s mRNA-1083
Influenza/COVID-19 combo
With Pfizer hitting a stumbling block, Moderna’s COVID-19/influenza vaccine, mRNA-1083, could be the first such combination vaccine to reach the market. In June, the company posted results from a Phase III trial that showed mRNA-1083 produced a strong immune response against both COVID-19 and influenza. In releasing the results, Moderna also became the first and, due to Pfizer/BioNTech’s struggles, only company to date to post positive Phase III results for a combination COVID-19/influenza vaccine.
The efforts by both Pfizer/BioNTech and Moderna can be seen as a strategy to extend the sales enjoyed by the standalone COVID-19 vaccines. One of the obvious marketing benefits would be the ability to provide the vaccine annually, each flu season. An additional selling point could be improved efficacy over existing vaccines, with Moderna stating that its combination vaccine candidate was more effective at providing immunity in adults over the age of 50 than competing influenza and COVID-19 shots.
Moving forward, Moderna plans to add its newly approved RSV vaccine to the combination, creating a triple shot against all three infectious diseases.
GSK/CureVac’s GSK4382276 and GSK4388067
Influenza and, separately, COVID-19
GSK is also targeting both influenza and COVID-19, though currently with separate products. In July, the British multinational bought the global rights to develop CureVac’s investigational mRNA vaccines against COVID-19 (GSK4388067) and influenza (GSK4382276), with the option to develop a combination and an additional vaccine against avian flu. GSK4388067 and GSK4382276 are both currently in Phase II trials and are therefore not too far behind their rivals. On securing full rights to the vaccines, GSK Chief Scientific Officer Tony Wood said in a statement that the company would apply its capabilities “to deliver these promising vaccines at pace.”
Moderna’s mRNA-4157
Head and neck cancer and melanoma
Oncology is one of biopharma’s key markets, and if mRNA vaccines can prove effective in the space, it could be a validation of the technology’s broader therapeutic and commercial potential. Moderna is developing mRNA-4157, a therapeutic vaccine currently being explored in Phase III. The vaccine is being developed in partnership with Merck and paired with Merck’s Keytruda in hopes that it will be able to boost the efficacy of the PD-1 inhibitor to provide a greater anti-tumor effect. The product is currently being trialed in various oncology indications, including head and neck cancer and melanoma.
Heller said that though McKinsey is seeing significant investment go into the therapeutic vaccine space, particularly for those targeting oncology, the “business case needs to be proven.” She added that should mRNA vaccines prove to be effective in the space McKinsey expects a number of follow-on assets to emerge, which could target other indications such as rare diseases. For the moment, the main focus of the vaccine pipeline remains infectious disease and respiratory conditions, Heller said.
Moderna’s mRNA-1647
Cytomegalovirus
Finally, Moderna is developing mRNA-1647 for cytomegalovirus (CMV), the most common infectious cause of birth defects in the U.S. The vaccine is currently being evaluated in Phase III for primary CMV infection in women 16 to 40 years of age.
The first interim analysis of the vaccine’s efficacy is expected by the end of 2024, Moderna stated in March. The company has also advanced indication expansion studies in adolescents 9 to 15 years old and in adult transplant patients. In Phase II results, antigen-specific immune responses were observed at all dose levels in both CMV-seronegative and -seropositive participants, with the vaccine also being found to be generally safe and well-tolerated.
There are currently no approved vaccines to prevent congenital CMV and no treatments for CMV in pregnancy. The virus is typically harmless to adults but can cause a range of health problems in babies and people with a weakened immune system.
