FDA Refusal-to-File Resets mRNA Flu Strategy

Agency’s decision signals tougher trial standards for seasonal vaccine approvals as pandemic-era flexibility recedes  

12 Feb 2026

The US Food and Drug Administration has declined to review a late-stage application for an mRNA-based seasonal influenza vaccine, signalling a shift towards stricter evidentiary standards in the post-pandemic market.

In February, the regulator issued a refusal-to-file letter to Moderna, stating that the company’s submission did not meet the requirements needed to begin a formal review. The agency cited shortcomings in the design of the pivotal trial, notably the absence of a head-to-head comparison with what it considers the most appropriate comparator vaccine for older adults. The FDA did not raise safety concerns.

A refusal-to-file decision differs from a rejection following a full scientific assessment. It indicates that regulators believe essential elements are missing from the application. In this case, the agency determined that without direct comparative data, the filing did not satisfy the threshold for evaluation.

The decision is being closely watched across the industry. During the Covid-19 pandemic, vaccine approvals were often accelerated under emergency conditions. As that urgency fades, applications are increasingly assessed under conventional standards that emphasise rigorous trial design, appropriate comparators and clear clinical differentiation.

Seasonal influenza is a mature and competitive market, particularly among older adults, where high-dose and enhanced vaccines dominate prescribing patterns. Demonstrating advantage over existing products is therefore central to regulatory and commercial success.

The implications extend beyond a single programme. Other groups developing mRNA-based vaccines, including Pfizer and BioNTech, are likely to face similar scrutiny over study design and endpoint selection. Regulatory engagement earlier in development is becoming more critical, especially in established vaccine categories.

Investors have responded by reassessing execution risk in the influenza segment. Some analysts suggest capital may shift towards therapeutic areas with clearer unmet need, such as oncology or rare diseases, where clinical pathways and competitive dynamics differ.

The episode does not undermine the broader scientific promise of mRNA technology. Instead, it highlights a higher evidentiary bar. For vaccine developers, future approvals are likely to depend as much on precise trial strategy and regulatory alignment as on platform innovation itself.