FDA Rejects Moderna’s Flu Vaccine Review Over Trial Design

Moderna Inc. announced on Tuesday that the U.S. Food and Drug Administration has refused to review its application for an experimental seasonal flu vaccine called mRNA-1010. The FDA's decision rests on the vaccine's Phase 3 trials using a standard-dose flu shot as the comparator, which the agency now says does not meet the bar for an adequate study. Moderna, based in Cambridge, Massachusetts, had used a priority review voucher to speed up the process, but the FDA sent a refusal-to-file letter instead.

Background

Moderna rose to fame during the COVID-19 pandemic with its mRNA vaccine, one of the first approved for emergency use. That success pushed the company to apply the same technology to other diseases, including the flu. Flu shots save lives each year, but they are not perfect. The viruses change, and protection can wane, especially for older adults. Moderna aimed to improve on that with mRNA-1010, targeting people 50 years and older.

The company ran two large Phase 3 trials with a total of 43,808 participants. These studies compared mRNA-1010 to existing flu vaccines. Both trials hit their main goals, showing the mRNA shot worked better in preventing flu than the controls used. Moderna worked closely with the FDA before starting these trials. In April 2024, the agency gave written feedback that allowed using a standard-dose flu vaccine as the comparator. Later, in August 2025, after the trials wrapped up, Moderna met with FDA officials again. The agency asked for extra data on the comparator but gave no sign it would block the review.

Moderna submitted its biologics license application late last year, hoping for quick approval thanks to the priority voucher. This tool lets companies pay for faster review, often cutting months off the timeline. The FDA's Center for Biologics Evaluation and Research, led by Director Vinayak Prasad, issued the refusal letter. It pointed only to the comparator choice, saying the study lacked an 'adequate and well-controlled' arm that reflects the 'best-available standard of care.' The letter raised no issues with the vaccine's safety data or how well it worked.

Key Details

The refusal letter specifies that Moderna's trials used a licensed standard-dose seasonal flu vaccine against mRNA-1010. The FDA said this does not match current standards, particularly for older adults who often get higher-dose shots for better protection. Moderna notes that FDA rules and guidance on flu vaccines do not require a 'best-available' comparator. The company included extra analyses from a third trial, called P303 Part C, which pitted mRNA-1010 against a high-dose flu vaccine in people 65 and older. Even so, the FDA stood firm.

Trial Results and Design

The two main Phase 3 studies enrolled thousands of adults. They measured flu prevention through lab-confirmed cases. mRNA-1010 showed statistical superiority over the standard shots in both. Safety profiles matched expectations for mRNA vaccines, with common side effects like sore arms and fatigue. No new red flags emerged. The FDA had signed off on the study designs before they began, making the reversal a surprise to Moderna.

Moderna posted the full FDA letter on its website for anyone to read. The company wasted no time responding. It requested a Type A meeting, the fastest kind regulators offer for big issues. These meetings happen within 30 days and aim to clear up roadblocks. Moderna wants straight answers on how to move forward.

"Refusal to review the submission is inconsistent with feedback at pre-Phase 3 and pre-submission consultations; Moderna has requested a Type A meeting to understand the path forward." – Moderna Inc. statement

Meanwhile, the vaccine's application is moving ahead elsewhere. Regulators in the European Union, Canada, and Australia have accepted it for review. Moderna plans submissions in more countries this year. The company eyes first approvals in late 2026 or early 2027, depending on those processes.

What This Means

For Moderna, this setback delays a key product. The flu vaccine is part of its plan to grow beyond COVID shots. Sales of those have dropped as the pandemic fades, leaving the company hunting for new revenue. A flu vaccine could bring in billions yearly if approved, especially for older adults. Moderna also eyes a combo COVID-flu shot down the line, but that depends on standalone success. The firm pulled a prior combo application to focus here.

The FDA's move highlights its push for tougher standards in vaccine trials. Regulators want head-to-head comparisons with top existing options, not just any licensed shot. This could slow other mRNA flu efforts from rivals. It also spotlights debates over what counts as 'adequate' evidence. Moderna argues its data is solid and meets prior agreements, but the FDA disagrees on the benchmark.

Investors watched closely Tuesday. Moderna's stock, traded as MRNA on Nasdaq, felt pressure from the news. The company stressed no change to its 2026 financial plans. It still projects breaking even by 2028, banking on flu and other vaccines. Recent flops, like a cytomegalovirus shot in Phase 3, add urgency to get mRNA-1010 right.

Patients and doctors await better flu options. Each winter, flu hospitalizes tens of thousands, mostly seniors. An mRNA vaccine could offer stronger, longer protection with quicker updates for new strains. While the U.S. path is blocked for now, global reviews keep hope alive.

Moderna stays focused. Its team prepares for the Type A meeting, ready to tweak plans if needed. The full story depends on that talk and what regulators say next. For now, mRNA-1010 sits in limbo stateside, but advances abroad.