Influenza Vaccine, Adjuvanted(Seqirus GmbH)

Facing an investigation from the European Commission (EC) over its "misleading" influenza vaccine campaign, Sanofi has offered to stop telling healthcare professionals (HCPs) its Efluelda jab is safer or more effective than CSL Seqirus' rival flu shot Fluad, among other promises.The French drugmaker's proposed resolution comes less than two weeks after the EU regulator opened a probe to determine whether Sanofi disparaged Fluad — the only other flu vaccine, besides Efluelda, recommended for vulnerable patients with risk factors — and thus violated anticompetitive rules.The EC said there are "indications" that since 2024, Sanofi's HCP-targeting communication campaign in Germany and France — two markets where Efluelda is considered to hold a dominant position — misrepresented national vaccine recommendations and the supporting data for Fluad.Sanofi allegedly claimed the evidence behind Fluad is "weaker" than that for Efluelda, while also suggesting German vaccine recommendations for CSL's shot are "subject to unresolved scientific objections from medical professional societies."To address the anticompetitive concerns, the EC said Wednesday that Sanofi has offered to post a statement on its website acknowledging that Efluelda and Fluad both have "a robust evidence base" and are recommended equally for elderly individuals in Germany. A separate statement on its French website would clarify that the two shots are "equivalent" under the country's recommendations. In future communications with HCPs about flu vaccines, Sanofi said it will not criticise, cast doubt on, or contradict a country's vaccination recommendations, nor will it portray Fluad or its supporting data negatively.The EC is now fielding feedback on Sanofi's proposal, with comments due by Aug. 21. If the regulator accepts the pharma's commitments, they would remain in effect until March 2030, and any violation on Sanofi's part could result in a fine of up to 10% of its worldwide annual turnover, or a periodic penalty payment of 5% per day of its daily turnover for every day of non-compliance.

Caught in the crossfire of the US's tumultuous and controversial vaccine policy overhaul, Moderna is the latest drugmaker stunned by a negative decision from the FDA that seemed to contradict earlier feedback. The biotech said Tuesday it received a refusal-to-file (RTF) letter from the FDA's Center for Biologics Evaluation and Research (CBER) after using a priority review voucher to speed along its regulatory filing for mRNA-based influenza vaccine candidate mRNA-1010, submitted in January.The letter, signed by CBER Director Vinay Prasad, did not identify any issues with mRNA-1010's safety or efficacy. Instead, the FDA's decision not to review the vaccine's application was based on the company's use of a licensed seasonal flu vaccine comparator in clinical studies. "It should not be controversial to conduct a comprehensive review of a flu vaccine submission that uses an FDA-approved vaccine as a comparator in a study that was discussed and agreed on with CBER prior to starting," Moderna CEO Stéphane Bancel said in a company release.According to Moderna, the letter cited the lack of an "adequate and well-controlled" study with a comparator arm that "does not reflect the best-available standard of care." However, the biotech argued that the RTF letter was "inconsistent with previous written communications from CBER," pointing to feedback it received on its Phase III study protocol.In an April 2024 note, CBER wrote that "it would be acceptable to use a licensed standard dose influenza vaccine as the comparator," though it recommended the drugmaker instead use a vaccine recommended for adults ages 65 and up by the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP), such as Fluzone HD, Fluad or Flublok. The agency concluded that if Moderna proceeded "with using a standard dose influenza vaccine comparator in participants ≥65 years of age, we agree with your plan to include statements in the Informed Consent Form." According to the drugmaker, CBER did not flag any issues with the study protocol before it was launched in September 2024 — but did so after the Phase III efficacy trial had finished and met its agreed-upon primary endpoints. In the study, which recruited 40,817 participants aged 50 and older, mRNA-1010 achieved a relative vaccine efficacy against influenza illness of 26.6% compared to Fluarix, a flu shot marketed by GSK.Following a pre-submission meeting with CBER in August 2025, Moderna said the agency requested that supportive analyses on the comparator be included in the submission, noting that it would be a "significant issue during review of your BLA." The drugmaker did so, and also shared data from a separate Phase III trial that evaluated mRNA-1010's safety and immunogenicity against a licensed high-dose influenza vaccine. In that trial, the mRNA shot demonstrated superior seroconversion rates and geometric mean titre ratios against all strains included in the vaccine."At no time in the pre-submission written feedback or meeting did CBER indicate that it would refuse to review the file," Moderna said. It has requested a Type A meeting with CBER "to understand the basis for the RTF letter." The drugmaker noted that regulators in the EU, Canada and Australia have all accepted its mRNA-1010 application for review, and more global submissions are expected this year. Vaccines in the crosshairs The RTF letter is the latest setback for Moderna since the US began reworking its vaccine policies under the direction of Health and Human Services (HHS) Secretary Robert F. Kennedy Jr., who has shepherded stricter vaccine development guidelines and an overhaul of the CDC's childhood vaccine schedule (see – ViewPoints: 'It's only going to get worse' — Offit's 2026 vaccine outlook).Amidst the flurry of changes in the past year, mRNA technology in particular has come under fire. In August, HHS cancelled funding for 22 mRNA vaccine programmes, including Moderna's experimental mRNA-based bird flu jab. At the time, Kennedy said the wind-down of agency support for the technology was because "the data show these vaccines fail to protect effectively against upper respiratory infections like COVID and flu," though he did not provide any data to support his claim.Increased scrutiny on mRNA-based vaccines also prompted Moderna last year to withdraw its FDA application for mRNA-1083, a combination influenza/COVID-19 candidate, based on a request for additional Phase III flu efficacy data. The biotech had planned to submit a filing for the combo vaccine once the review for mRNA-1010 was under way. Fellow vaccine developer Pfizer also has an mRNA flu shot in late-stage development, though it's unclear whether it will also be hit with an RTF letter. In a Phase III trial, the pharma's jab demonstrated superiority over Fluzone on the study's primary endpoint of relative efficacy.FDA about-faceOutside of the vaccine landscape, other drugmakers have raised concerns with unexpected FDA rejections on products that succeeded in pivotal testing. Most recently, Regenxbio's Hunter syndrome gene therapy received a complete response letter (CRL), though the company asserted on Monday that it had addressed all issues raised "through the submission of additional data and responses to numerous information requests."Regenxbio and Moderna are part of a growing cohort of companies who have called out inconsistent feedback from the FDA.Sanofi's tolebrutinib was rebuffed by the FDA late last year in what it called a "significant and meaningful change in direction from the feedback the agency previously provided." Similarly, Corcept Therapeutics' relacorilant was rejected in December in what the company called a "surprise and disappointment" in the face of a pivotal trial that had met its primary endpoint.For a breakdown on other high-profile rejections from the agency last year — including those handed down to Ultragenyx Pharmaceuticals, Capricor Therapeutics, Atara Biotherapeutics and Replimune — see Vital Signs: The FDA's 2025 report card.