Moderna said Thursday it plans to talk to regulators about the next steps after showing its next-generation candidate is more efficacious in adults than the biotech’s existing Spikevax COVID-19 shot.
Moderna said Thursday its next-generation COVID-19 vaccine achieved higher efficacy in adults in a Phase III trial than its existing Spikevax shot.
Spikevax, Moderna’s approved COVID-19 shot, is an mRNA vaccine that encodes a full-length SARS-CoV-2 S protein. The vaccine achieved 94.5% efficacy in its pivotal trial in 2020. However, real-world use revealed scope to make Spikevax more effective, notably against new variants, and to simplify logistics. The next-generation mRNA-1283 vaccine is Moderna’s attempt to deliver those improvements.
Unlike Spikevax, mRNA-1283 encodes two segments of the S protein that contain key SARS-CoV-2 neutralization epitopes, namely the N-terminal domain and receptor binding domain. Jacqueline Miller, senior vice president of infectious disease development at Moderna, explained the thinking behind the design at the biotech’s vaccine day in March 2024.
“The most effective antibodies are generated against the receptor binding domain and the N-terminal domain,” Miller said. “We believe this is really going to help enable combination vaccines, because we found that with an adapted antigen, we are able to reduce interference and we also think that this will allow us to offer a more competitive COVID-19 vaccine.”
Moderna reported that mRNA-1283 achieved a higher immune response than Spikevax in a Phase III trial in March. The latest update shows how the superior immune response translated into protection against COVID-19.
The efficacy of the investigational vaccine was non-inferior to Spikevax in the overall population, which enrolled 11,400 people aged 12 years and up, and was higher than the first-generation shot in adults. Moderna said it saw “a consistent trend” in the subset of adults aged 65 and older. The biotech reported the highest titers in older subjects when it published the immune response data in March.
The mRNA-1283 candidate matched or beat the efficacy of Spikevax despite being given at a lower dose, 10μg, than the approved product, 50μg. Moderna contends the shorter mRNA length of mRNA-1283 facilitates higher levels of protein expression at similar or lower doses than Spikevax. The design of mRNA-1283 could also allow the vaccine to be stored for longer under refrigeration.
The investigational vaccine had a similar safety profile to Spikevax in the latest study, with injection site pain, fatigue, headache and muscle aches the most commonly solicited side effects. Moderna plans to talk to regulators about the next steps for the program.
The update comes days after Moderna reported Phase III data on its combined vaccine against COVID-19 and influenza. The combined vaccine contains the next-generation COVID-19 vaccine, reflecting Moderna research that shows there is less interference with the adapted antigen. Moderna’s combination vaccine achieved superior immune responses against COVID-19 and influenza than licensed products.
Nick Paul Taylor is a freelance pharmaceutical and biotech writer based in London. He can be reached on LinkedIn.
