FDA holds clinical trial enrollment for Tolebrutinib Phase 3 Studies

June 30, 2022
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Patient enrollment of phase III tolebrutinib trials paused in the U.S.

Paris, June 30, 2022. The U.S. Food and Drug Administration (FDA) has placed Phase 3 studies of tolebrutinib in multiple sclerosis (MS) and myasthenia gravis on partial clinical hold. As a result, new enrollment in the United States (U.S.) is paused, and participants in the U.S. who have been in the trial for fewer than 60 days shall suspend study drug. Importantly, U.S. participants who have completed at least 60-days in the trial should continue treatment.

The FDA action was based on a limited number of cases of drug-induced liver injury that have been identified with tolebrutinib exposure in Phase 3 studies. The majority of the impacted patients were determined to have concurrent complications known historically to predispose to drug-induced liver injury. Importantly, the elevations of laboratory values used for monitoring liver injury were reversible after drug discontinuation for all cases. Following earlier dialog with FDA about these cases, study protocols were revised in May 2022 to update the monitoring frequency, and enrollment criteria were revised to exclude preexisting risk factors for hepatic dysfunction.

Enrollment in the clinical program continues with the revised study protocols and enhanced safety monitoring in countries outside of the U.S. Sanofi is working closely with the independent data monitoring committee members and investigators around the world to evaluate the effectiveness of safety measures. The program in MS has been enrolling patients since 2019 and includes more than two-thousand patients currently on tolebrutinib therapy with durations of treatment as long as 3 years.

Sanofi remains confident in the future of tolebrutinib as a potentially transformative oral treatment option for people living with MS.

About tolebrutinib

Tolebrutinib is an investigational brain-penetrant and bioactive Bruton’s tyrosine kinase (BTK) inhibitor that achieves CSF concentrations needed for targeting B lymphocytes and microglial cells. Tolebrutinib is being evaluated in Phase 3 clinical trials for the treatment of relapsing forms of MS (RMS), non-relapsing secondary progressive MS (nrSPMS), primary progressive MS (PPMS), and myasthenia gravis (MG) and its safety and efficacy have not been evaluated by any regulatory authority worldwide. For more information on tolebrutinib clinical trials, please visit www.clinicaltrials.gov.

About the tolebrutinib Phase III trials

GEMINI 1 (EFC16033): RMS Study of BTKi tolebrutinib
GEMINI 2 (EFC16034): RMS Study of BTKi tolebrutinib
PERSEUS (EFC16035): PPMS Study of BKTi tolebrutinib
HERCULES (EFC16645): Non-relapsing SPMS Study of BTKi tolebrutinib
URSA (EFC17262): Efficacy and Safety of Tolebrutinib in Adult Participants With Generalized Myasthenia Gravis

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