Moderna's Next-Gen COVID-19 Vaccine Shows Promise Against Latest Variant

Moderna has reported encouraging early results from human trials of its updated COVID-19 vaccine, mNEXSPIKE, demonstrating strong immune responses against the rapidly spreading LP.8.1 sublineage of SARS-CoV-2. The pharmaceutical company's latest data underscores the potential of its next-generation vaccine to offer enhanced protection against emerging virus variants.

Clinical Trial Results

In a postmarketing clinical study, Moderna's mNEXSPIKE vaccine induced an average greater-than-16-fold increase in neutralizing antibodies against the LP.8.1 sublineage in individuals 12 years of age or older. This response significantly outperformed the company's first-generation mRNA vaccine, Spikevax, which generated a greater-than-eightfold increase in LP.8.1-neutralizing antibodies across the same age groups.

The updated mNEXSPIKE formula, specifically designed to target the LP.8.1 variant, received FDA approval in August 2025 for use in high-risk individuals aged 12 to 64 and all adults 65 and older. Moderna is currently conducting two studies as part of its postmarketing commitments: a single-arm phase 3b/4 study in the approved age groups and a placebo-controlled phase 4 trial in adults ages 50 to 64 without high-risk conditions.

Regulatory Landscape and Future Requirements

The FDA's recent approvals for LP.8.1-adapted COVID shots, including Moderna's mNEXSPIKE, were primarily based on preclinical data. This approach followed a period of uncertainty regarding the need for additional in-human clinical trials for updated COVID vaccines. Moderna emphasized that the latest clinical data "underscore the predictability of preclinical data" that supported the FDA's approval of the new mNEXSPIKE formula.

However, the regulatory landscape may be evolving. FDA's top vaccines official, Vinay Prasad, M.D., has indicated that new requirements may be implemented for vaccine makers seeking to promote coadministration of multiple shots. In a decision memo related to Pfizer and BioNTech's updated COVID shot Comirnaty, Prasad stated that randomized, controlled trials with clinical disease outcomes as the primary endpoint would be required for any claims of coadministration or specific vaccine sequences.

As the pharmaceutical industry continues to adapt to the evolving nature of the SARS-CoV-2 virus, these developments highlight the ongoing efforts to enhance vaccine efficacy and navigate the complex regulatory environment surrounding COVID-19 immunizations.