The development of mRNA-1010 was a pivotal move for Moderna to build a diversified product portfolio in the "post-COVID era".

Unlike traditional inactivated or attenuated vaccines, mRNA vaccines work by introducing mRNA sequences encoding key antigenic proteins of the influenza virus into human cells, which directly instruct the cells to synthesize these antigens. This mimics the natural infection process and effectively stimulates the human body to produce a comprehensive humoral and cellular immune response.

Two Phase 3 studies of mRNA-1010 (the P303 immunogenicity study and the P304 efficacy study) were designed to evaluate its protective efficacy, immunogenicity and safety in adults, especially the elderly population. The study results showed that the data met the primary prespecified endpoints.

Compared with approved traditional influenza vaccines, vaccination with mRNA-1010 induced a stronger and broader spectrum of immune responses, demonstrating protective potential against multiple influenza virus strains including influenza A and B, with a favorable overall safety profile.

According to the timeline disclosed by Moderna, the trajectory of the shifting regulatory stance is troubling.

In 2024, the FDA clearly stated in written feedback that the use of a licensed standard-dose influenza vaccine as a control for the Phase 3 trial was acceptable. However, in August of the following year, in pre-submission feedback, the FDA first hinted that the adequacy of the control arm would be a major issue in the review. Ultimately, in February 2026, this once green-lit application was rejected.

The crux of the controversy lies in the definition of the "standard". The FDA argued that for trials in adults aged 50 and above, the control arm should use the high-dose or adjuvanted influenza vaccines recommended for people over 65, which it deemed the "best available standard of care".

Moderna, in response, countered that the use of a standard-dose vaccine as a control has long been a precedent in key influenza trials. Moreover, in more than a year of prior communications, the FDA never hinted that this would be a reason for refusing review, nor is there any regulatory precedent requiring the control arm to be the "best available option".

The ripple effect of mRNA-1010's rejection is devastating. The marketing progress of mRNA-1083, a combined influenza and COVID-19 vaccine based on the same technical platform, has consequently ground to a halt. Its influenza component fully adopts the quadrivalent influenza vaccine technical platform of mRNA-1010 (targeting influenza A H1N1, H3N2 and two influenza B strains), with only an additional COVID-19 vaccine component added.

Long before mRNA-1010 yielded positive Phase 3 results, Moderna had voluntarily withdrawn the marketing application for mRNA-1083, explicitly stating that it needed to wait for the complete efficacy data of mRNA-1010 as the basis for the approval of the combined vaccine.

This retrospective change of standards has created tremendous uncertainty. As described by industry media, companies are caught in a general anxiety over "regulatory chaos". External investors such as Blackstone Life Sciences, which provided up to $750 million in financing for the mRNA-1010 project, are undoubtedly facing a predicament where their investment logic has been upended by non-commercial risks.

The storm originated at the highest level.

In February 2025, Robert F. Kennedy Jr., a long-time vaccine skeptic, took the helm of the U.S. Department of Health and Human Services (HHS) and set the tone for a comprehensive overhaul.

In March of the same year, Peter Marks, Director of CBER, announced his resignation. A veteran scientist hailed as the industry's anchor, Marks stated in his resignation letter that the new leadership demanded compliance with their misinformation and lies, rather than science-based facts and transparency. His departure sent Moderna's stock price plummeting by more than 12% in a single day, which the market interpreted as a sign of the collapse of the scientific independence of regulation.

Policy upheavals followed one after another.

Subsequently, in May, the FDA released a brand-new approval framework for COVID-19 vaccines, completely abandoning the accelerated pathway based on immunogenicity biomarkers and instead requiring large-scale clinical endpoint trials for each age and risk subgroup. This requirement, criticized by experts as "unnecessary and unethical", has greatly increased R&D costs and complexity.

At the same time, institutions designed to provide independent scientific advice have also undergone systematic restructuring.

By June, Kennedy unilaterally dismissed all experts on the Centers for Disease Control and Prevention's (CDC) Advisory Committee on Immunization Practices (ACIP), and in the following months, filled the committee with several members who lack traditional vaccinology backgrounds but are known for questioning routine vaccines (such as the measles vaccine).

These measures, together with HHS's abrupt termination of multiple mRNA R&D projects funded by the Biomedical Advanced Research and Development Authority (BARDA), have jointly created a regulatory environment that is highly hostile to vaccine innovation, particularly mRNA technology.

Against this backdrop, the review decisions of regulatory officials represented by Prasad have inevitably aligned with the upper-level political will. Coupled with revelations by The Wall Street Journal that he is facing multiple personnel complaints within the agency, Prasad has once again been thrust into the eye of the storm.

Citing anonymous sources, The Wall Street Journal reported that Prasad is the subject of internal complaints involving "sexual harassment, retaliation against subordinates, and verbal abuse of employees", in addition to large travel expenses.

A senior FDA official told Endpoints News that Prasad has assigned meaningless work to certain subordinates and verbally attacked employees. Prasad himself has not responded to requests for comment, nor have HHS and the FDA.

Last year, Prasad resigned from the FDA over a similarly controversial decision on Sarepta's gene therapy for Duchenne muscular dystrophy (DMD), but returned to his post a few weeks later.

Furthermore, according to Endpoints News, Prasad has also claimed that COVID-19 vaccines have caused a large number of child deaths. However, the FDA has yet to release an analysis report on these so-called death cases, which was originally scheduled to be published at the end of last year.

The FDA's refusal to accept Moderna's mRNA influenza vaccine is just a microcosm of the agency's larger communication crisis over the past nine months.

Moderna is far from the only company to feel the impact. Capricor's cell therapy for Duchenne muscular dystrophy, Biohaven's drug for spinocerebellar ataxia, and uniQure's gene therapy for Huntington's disease have all seen their approvals delayed due to the FDA's flip-flopping guidance.

An extreme case comes from Sarepta. Two adolescent patients died after receiving its approved DMD gene therapy Elevidys, yet the FDA informally recommended the company to suspend shipments—a request that Sarepta, like the public, learned about only from media reports.

The core of this chaos points to the FDA's CBER, the division responsible for the review of biological products such as cell and gene therapies and vaccines, which places particular emphasis on clinical trial design. However, for rare disease patients with extremely small patient populations, traditional randomized controlled trials (RCTs) are often not feasible.

CBER's earlier guidelines had relented, acknowledging that biomarkers could be used as surrogate endpoints, and single-arm trials were also included in multiple documents encouraging accelerated approval.

But in actual implementation, past and present issues have been settled together. uniQure's AMT-130 had received written approval from the FDA that natural history external controls combined with single-arm trial data could be used to apply for accelerated approval. However, in November 2025, the FDA reversed this position, stating that the data was insufficient to support a Biologics License Application (BLA). Atara Biotherapeutics' cell therapy Ebvallo was also rejected due to its single-arm study, with the company directly accusing the FDA of "inconsistency" in a press release.

"Regulations are issued but fail to be implemented," noted Roberta Duncan, former Chief Scientific Officer of Arcturus Therapeutics, referring to the rational mechanistic pathway proposed by The New England Journal of Medicine in 2025—a review channel specifically designed for ultra-rare diseases—which remains nothing more than paper talk to this day.

Of course, many company executives have defended CBER's caution, stating that the FDA is striking a balance between safety and efficiency with extremely rigorous pharmacovigilance.

The U.S. HHS has also publicly backed Prasad, with a spokesperson stating that the FDA's rejection was due to Moderna's failure to comply with the 2024 guidelines by not using CDC-recommended vaccines as controls for safety and efficacy comparisons. Moderna pointed out that the FDA's vaccine development guidelines have never required the use of the "best standard of care" as a control.

An anonymous senior FDA official revealed that Moderna used an inferior control to exaggerate the product's efficacy, and suggested that refiling with a focus on the 50-64 age group would have a higher success rate. The official stated that the FDA has not closed the door to resubmission, and if approved eventually, physicians can use the vaccine flexibly, but Moderna needs to "show humility".