Drugs

CRL for Sanofi Multiple Sclerosis Drug

FDA has issued a complete response letter (CRL) for Sanofi/Genzyme’s tolebrutinib NDA to treat non-relapsing secondary progressive multiple sclerosis (MS) in adults. The just-released CRL says the agency rejected the submission due to an unusually high risk of severe drug-induced liver injury (DILI) and uncertainties regarding efficacy in the targeted patient population.

FDA acknowledged Genzyme’s proposed Risk Evaluation and Mitigation Strategy (REMS) and efforts to implement enhanced liver monitoring, but it determined that the REMS would not adequately mitigate the risk of severe DILI. “Even with weekly monitoring, the predicted postmarket rate of severe DILI associated with tolebrutinib remains substantial,” the CRL states. The agency letter also notes substantial uncertainties on the efficacy from based on data from the company’s pivotal Phase 3 trial (Study EFC16645).

Given these factors, FDA concludes that no clearly defined patient population exists in which the benefits of tolebrutinib outweigh the serious risk of severe DILI. The agency emphasized that therapies with high safety risks require strong evidence of benefit, which, in this case, was not established.

A company statement says Sanofi had understood that FDA expected the PDUFA action date to extend beyond the planned 12/28/2025, and that further agency guidance was expected by the end of the first quarter of 2026.

“Today’s FDA decision is a significant and meaningful change in direction from the feedback the agency previously provided to Sanofi,” the statement says. “We are very disappointed by the agency’s action. Disability progression remains a large unmet medical need in MS, and tolebrutinib was previously awarded breakthrough therapy designation by FDA in recognition of its potential to address this critical gap. We believe that FDA should also take the advice of scientific experts, clinicians, and patients in this matter to ensure all perspectives are considered. We remain committed to working with FDA to find a path forward for tolebrutinib and ultimately serve the MS community.”

Tolebrutinib is described as an investigational, oral, brain-penetrant Bruton’s kinase inhibitor specifically designed to target smoldering neuroinflammation, a key driver of disability progression in MS. Sanofi says the mechanism addresses the underlying pathology of progressive MS by targeting the inflammatory processes that contribute to neurodegeneration and disability accumulation.

Gupta Raises Concerns About Overton’s Independence, Ideology

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FDA Classifies Boston Scientific Imager II Catheter Recall as Class I

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FDA Approves Gazyva for Childhood-Onset Idiopathic Nephrotic Syndrome

FDA has approved Roche’s Gazyva (obinutuzumab) for reducing the risk of relapse in adults and children aged 2 and older with frequently relapsing or steroid-dependent, childhood-onset idiopathic nephrotic syndrome who are in remission. The expanded approval covers the use of the CD20-directed antibody beyond its existing

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Gupta Raises Concerns About Overton’s Independence, Ideology

Overton Confirmation Remains Uncertain After Senate Hearing

FDA Classifies Boston Scientific Imager II Catheter Recall as Class I

FDA Approves Gazyva for Childhood-Onset Idiopathic Nephrotic Syndrome