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FDA Places Hold on Recruitment in the U.S. for Phase 3 Studies of Experimental Tolebrutinib

June 30, 2022

Enrollment in the United States of people with MS in phase 3 studies of experimental tolebrutinib has been placed on hold by the U.S. Food and Drug Administration due to some cases of liver injury that occurred in people enrolled in these trials. The studies – called HERCULES, PERSEUS, GEMINI 1 and GEMINI 2 – are sponsored by Sanofi. In the affected people, discontinuing tolebrutinib reversed the elevated laboratory values used for monitoring liver injury, according to the sponsor’s press release  dated June 30, 2022.

Background: Tolebrutinib inhibits an enzyme called “Bruton’s tyrosine kinase,” reducing the activation of B cells, which are immune cells that play a role in the response that affects the brain and spinal cord in MS. Tolebrutinib also penetrates the brain and spinal cord and inhibits immune cells in the brain called microglia, which have been linked to MS progression. Tolebrutinib is one of several “BTK” inhibitors being tested in the MS pipeline.

Pause of Enrollment: According to the press release, new enrollment in the U.S. is paused, and treatment is being discontinued in participants in the U.S. who have been in the trial for less than 60 days. U.S. participants who have completed at least 60 days in the trial can continue to receive treatment and remain in the trial.

Study protocols were revised in May 2022 to increase monitoring for indications of liver injury and enrollment criteria were revised to exclude people who had preexisting risk factors for liver dysfunction. The study is continuing to enroll with these revisions outside of the United States.

Next Steps: If you are a participant in this study, and you have concerns, please reach out to the site at which you enrolled in the study. Or, for further information, please contact Sanofi via email,, or phone (US & Canada), 800-633–1610, option 6.

About Multiple Sclerosis

Multiple sclerosis is an unpredictable disease of the central nervous system. Currently there is no cure. Symptoms vary from person to person and may include disabling fatigue, mobility challenges, cognitive changes, and vision issues. An estimated 1 million people live with MS in the United States. Early diagnosis and treatment are critical to minimize disability. Significant progress is being made to achieve a world free of MS.


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