FDA Flags Liver Injury Risk In Sanofi's Rejected Multiple Sclerosis Drug

In December 2025, the U.S. Food and Drug Administration (FDA) issued a complete response letter (CRL) for Sanofi SA's (NASDAQ:SNY) new drug application of tolebrutinib to treat non-relapsing secondary progressive multiple sclerosis (nrSPMS) in adult patients.

The press release was thin on information related to the rejection. The FDA publicly shared the complete response letter, citing both efficacy and safety concerns.

The regulatory agency wrote that, "a favorable benefit-risk profile could not be established for any patient subpopulation."

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Unraveling FDA's Rejection Reasons

The FDA determined a serious risk of severe drug-induced liver injury (DILI) identified during clinical trials and noted that the risk could not be adequately mitigated by the proposed risk evaluation and mitigation strategy (REMS).

The FDA said that Sanofi said the benefit-risk profile was favorable for patients with nrSPMS because there currently aren't any approved treatments for the subpopulation.

FDA disagreed and wrote, "We were unable to identify a population for which the benefit could be clearly established and for which that benefit would be anticipated to outweigh the serious risk of severe DILI to support approval."

FDA's review identified six cases meeting Hy's Law criteria in the tolebrutinib Phase 3 development program out of approximately 2700 subjects, including one subject who died after requiring a liver transplant, which indicates a high level of hepatotoxic risk with tolebrutinib.

The letter also noted that in the first 6 months of double-blind treatment of Study EFC16645, 3.6% of tolebrutinib-treated subjects versus 1.9% of placebo-treated subjects experienced aminotransferases greater than 3 times the upper limit of normal.

Additionally, the regulator highlighted uncertainties about the analyses provided regarding slowing disability accumulation independent of relapse activities.

"Overall, substantial evidence of effectiveness has not been established in a clinically identifiable population for whom the benefits potentially outweigh the risks," the FDA said in the letter.

SNY Price Action: Sanofi shares were up 0.53% at $47.76 during premarket trading on Tuesday, according to Benzinga Pro data.

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