Sanofi Pauses Recruitment in All Phase 3 Trials of Tolebrutinib

Study participants already on tolebrutinib will continue treatment

Vanda Pinto, PhD avatar

by Vanda Pinto, PhD |

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Sanofi has decided to pause recruitment globally in its Phase 3 clinical trials of tolebrutinib, an experimental BTK inhibitor, based on recommendations from the independent data monitoring committee (iDMC) overseeing the trials.

The company has several ongoing studies investigating tolebrutinib’s effectiveness and safety, including one testing the investigational therapy in people with myasthenia gravis (MG) and two in patients with different types of multiple sclerosis (MS).

The U.S. Food and Drug Administration (FDA) recently placed a partial clinical hold on Phase 3 trials of tolebrutinib that ceased enrolling new participants in the U.S. This decision was based on a limited number of cases of drug-induced liver injury.

Now, although health authorities outside the U.S. have allowed the studies to continue under a modified protocol, which included excluding patients with preexisting liver problems, Sanofi will cease recruitment to focus on reviewing previous data and analyze the impact of the revised protocol.

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As recommended by the iDMC, all study participants already on tolebrutinib will continue to receive treatment according to the trial protocols.

“Patient safety remains our top priority as we continue to investigate the impact of tolebrutinib on liver function during this recruitment pause. We remain confident in the future of tolebrutinib as a potentially transformative oral treatment option for people living with MS and are working closely with regulatory authorities in order to resume active recruitment within [the last quarter of] 2022,” John Reed, MD, PhD, said in a press release. Reed is global head of research and development at Sanofi.

Tolebrutinib is an oral treatment that works by blocking an enzyme called Bruton’s tyrosine kinase, or BTK, and reducing the abnormal activation of antibody-producing immune B-cells, which are known to be involved in autoimmune diseases such as MG and MS.

The Phase 3 URSA trial (NCT05132569) is investigating the safety and efficacy of tolebrutinib in up to 154 patients, ages 18–85, with moderate-to-severe generalized MG. Participants will be assigned randomly to receive tolebrutinib or a placebo once daily for 26 weeks. This will be followed by a two-year open-label extension (OLE) period, in which all participants will be given tolebrutinib.

The main goal of the study is to evaluate changes in participants’ daily life, assessed using the MG-activities of daily living total score, as well as the incidence of side effects. Researchers also will evaluate the effects of treatment on other standardized measures of MG severity.

URSA is underway in several countries, including the U.S., Canada, China, Spain, Italy, and the U.K.

Sanofi emphasized that the decision to halt recruitment was not based on any new safety findings and that it will provide the FDA with the requested safety information by the end of September.