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Pressing for label change, vaccine giant Sanofi takes Seqirus influenza imbroglio to the FDA

Sanofi is challenging influenza rival Seqirus on the regulatory level, arguing labels for two of the CSL Limited subsidiary’s flu shots should be amended to reflect their mixed results in post-approval trials. Seqirus, for its part, says it stands behind the safety and efficacy of its vaccines.

Sanofi made its case to the FDA in a citizen petition published earlier this month. Its complaint hinges on Seqirus’ Fluad–an adjuvanted, trivalent flu shot that snagged accelerated approval in November 2015–and Fluad Quadrivalent, a quadrivalent formulation of the same vaccine that received a speedy green light in Feb. 2020.

For the quadrivalent formulation, Seqirus is on deck to wrap up a confirmatory study by March 31, 2024. Trivalent Fluad, meanwhile, scored accelerated approval in 2015, also on the condition that Seqirus demonstrate the vaccine’s efficacy in a post-approval trial.

Problem is, Seqirus used the quadrivalent formulation in its Fluad confirmatory trial, rather than the trivalent formulation that snagged approval, Sanofi argues. Even then, the quadrivalent formulation missed the mark in efficacy trial V118_18, Sanofi points out.

“Ultimately, the absolute vaccine efficacy was estimated to be 19.80%, which did not meet the pre-specified criterion of lower limit ≥ 40%,” Sanofi wrote in its petition. “The company explained this failure to meet its primary endpoint by stating that most influenza cases were caused by A/H3N2 strains and were antigenically unmatched to the vaccine strain.”

Fluad Quadrivalent did meet a secondary immunogenicity endpoint in the trial, Sanofi added.

The two years in which Seqirus ran Fluad’s confirmatory trial “proved to be challenging seasons to conduct efficacy and effectiveness studies because there was a predominant circulation of A/H3N2 influenza strains which were antigenically unmatched to the vaccine strains chosen by the World Health Organization (WHO),” a Seqirus spokesperson said over email.

The effect of the mismatch was “seen worldwide,” with overall effectiveness of all influenza vaccines lower in older adults–including that of Sanofi’s Fluzone High-Dose shot–the Seqirus spokesperson continued. One “inconclusive study” doesn’t paint the full picture of a seasonal flu shot’s efficacy, she added.

While its quadrivalent formulation missed the mark in V118_18, Seqirus subsequently sought accelerated approval of the new formulation, which it supported with another study Sanofi refers to as Immunogenicity Trial V118_20. That study compared Fluad Quadrivalent to the licensed trivalent formulation plus another adjuvanted trivalent shot containing an alternate flu strain.

“Ultimately,” Sanofi argues, “Immunogenicity Trial V118_20 met the primary endpoint requiring noninferior immunogenicity as compared to the aTIV formulations, but failed to meet the co-primary endpoint of immunogenicity criteria needed to support accelerated approval based on relevant [FDA] guidance.”

Because Fluad and Fluad Quadrivalent’s labels don’t reflect the shot’s confirmatory study struggles, Sanofi argues the labels are “inconsistent” with FDA regulations, guidance and precedents.

“Neither the labeling for Fluad, nor the labeling for Fluad Quadrivalent, refers to the failed absolute efficacy confirmatory study, Efficacy Trial V118_18, despite the fact that FDA labeling regulations and guidance repeatedly underscore the importance of labeling that informs the safe and effective use of the product, including by describing limitations of the available evidence,” Sanofi argued in its petition.

Sanofi cited precedent in GlaxoSmithKline’s influenza vaccine FluLaval, which it claims is “the only influenza vaccine besides Fluad that was approved through the accelerated approval pathway for which the confirmatory study required as a condition of approval was unsuccessful in meeting its primary endpoints.”

In that instance, the product’s label was updated to include “not only the subsequent successful confirmatory studies but also the initial unsuccessful confirmatory study, so as to accurately and completely portray the limitations of the existing effectiveness data,” Sanofi said.

Seqirus, for its part, told Fierce Pharma it stands by the “demonstrated safety and efficacy profiles” of its vaccines, including Fluad Quadrivalent. “Furthermore, we have confidence in the regulatory framework that provides for rigorous review of vaccine candidates and is the foundation of the public’s trust in vaccines,” the company’s spokesperson said.

“We are disappointed to see Sanofi Pasteur, a company with a long-standing history in vaccines, attempt to erode confidence in proven public health institutions, processes and tools,” Seqirus’ spokesperson continued. “We believe that Sanofi Pasteur continues to attempt to improperly influence an independent scientific process which should be focused on all of the available data and public health considerations and not on the commercial aspirations of one manufacturer.

Meanwhile, last month, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) for the first time acknowledged the benefits of an enhanced flu shot versus standard egg-based influenza vaccines, Seqirus said. Fluad Quadrivalent is one of three vaccines ACIP classifies as enhanced, along with Sanofi’s Fluzone High-Dose and Flublok.

Importantly, “ACIP clearly stated that the overall evidence directly comparing EIVs with one another—based on data including millions of patients and multiple seasons—does not indicate superiority of one EIV over the others,” Seqirus’ representative said.

Sanofi and Seqirus’ influenza imbroglio comes as Sanofi presses ACIP to revise its flu shot guidance for older adults. Specifically, the drugmaker wants ACIP to update its recommendations in favor of Sanofi’s Fluzone high-dose shot for adults ages 65 and older.