FDA Places Partial Hold on Phase 3 Clinical Trials of Tolebrutinib

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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The U.S. Food and Drug Administration (FDA) has placed a partial clinical hold on Phase 3 trials that are testing Sanofi’s experimental BTK inhibitor tolebrutinib.

The move affects a trial in people with myasthenia gravis (MG), as well as several studies evaluating tolebrutinib for different types of multiple sclerosis (MS).

Enrollment of new participants at study sites in the U.S. is now paused. For participants already in the trial, those who have been in the study for less than 60 days will stop taking the medication. Participants who have been in the study for at least 60 days will continue dosing uninterrupted.

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The FDA’s decision was based on “a limited number of cases of drug-induced liver injury that have been identified with tolebrutinib exposure in Phase 3 studies,” according to a company press release.

Most of the individuals who experienced liver injury had underlying conditions that are known to predispose them toward medication-induced liver injury, Sanofi noted. In all of the cases, markers of liver injury reversed after patients stopped taking tolebrutinib.

The trial protocols were revised in May to update monitoring frequency and add exclusion criteria related to liver injury, following earlier discussions with the FDA.

Outside of the U.S., enrollment in tolebrutinib clinical trials is continuing under the revised protocol. Sanofi said it is working closely with study investigators, and with a panel of independent experts tasked with ensuring the safety of clinical trial participants, to evaluate the effectiveness of new precautionary measures.

Tolebrutinib is an oral therapy designed to block the activity of Bruton’s tyrosine kinase (BTK), a protein that plays a key role in the survival and activity of antibody-producing B-cells, which behave abnormally in many autoimmune diseases like MG and MS.

The Phase 3 trial testing tolebrutinib in people with MG is called URSA (NCT05132569). The study, sponsored by Sanofi, seeks to enroll about 154 adults, ages 18–85, with moderate to severe generalized MG. The study is open to patients on standard care who are positive for anti-AChR or anti-MuSK — the two most common types of MG-driving antibodies.

Trial participants will be assigned randomly to take tolebrutinib or a placebo once daily for 26 weeks (about six months). Then, all participants will be given tolebrutinib for an additional two years.

The study’s main goal is to assess how treatment affects participants’ daily life, as assessed with the MG-activities of daily living total score. Other standardized measures of MG severity, as well as safety-related outcomes, also will be evaluated.

URSA is being conducted at sites in the U.S., Canada, China, Hungary, Spain, Poland, Italy, and the U.K.