Sanofi is stopping clinical development of Tolebrutinib for MG

Decision means Phase 3 URSA trial is being discontinued

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Sanofi is stopping the clinical development of tolebrutinib for treating myasthenia gravis (MG), the company announced in a recent press release.

The decision was made after “careful evaluation of the emerging competitive treatment landscape in MG,” according to Sanofi, and will result in discontinuing the Phase 3 URSA trial (NCT05132569), which was testing tolebrutinib in adults with generalized MG.

Clinical testing of tolebrutinib in people with multiple sclerosis (MS) is still ongoing.

Tolebrutinib is an oral small molecule designed to inhibit Bruton’s tyrosine kinase (BTK), an enzyme that plays an important role in the development and activation of B-cells, the immune cells responsible for producing antibodies. By inhibiting BTK, tolebrutinib may be able to prevent B-cells’ excessive activation that leads to self-reactive antibodies being produced in MG and other autoimmune diseases.

Tolebrutinib was first developed by Principia Biopharma, which licensed it to Sanofi in 2017. Sanofi later acquired Principia.

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Launched in 2021, the URSA trial was investigating the safety and effectiveness of tolebrutinib in up to 154 adults, ages 18-85, with moderate-to-severe generalized MG at sites in the U.S., Canada, China, Hungary, Spain, Poland, Italy, Japan, and the U.K.

Participants were randomly assigned to receive tolebrutinib or a placebo, once daily for 26 weeks, or about six months. URSA was also expected to have an open-label extension phase, wherein all the participants would receive tolebrutinib for up to two years.

In addition to safety, URSA’s main goal was to evaluate its impact on daily life, assessed using the MG-activities of daily living (MG-ADL) scale, after six months. Other measures of severity were also being assessed as secondary goals.

The U.S. Food and Drug Administration (FDA) placed a partial clinical hold on all Phase 3 trials of tolebrutinib last summer, including URSA and other trials in MS patients, due to some cases of reversible medication-induced liver injury. Most of the people affected had other underlying conditions that may have predisposed them to this type of injury.

With the pause, participants who had been in a study for fewer than 60 days had to stop using the medication, while those who had been treated for at least 60 days could continue it.

Enrollment of new patients in the trials was also paused in the U.S., while enrollment in sites outside the U.S. could continue under a new safety and monitoring protocol.

Following a recommendation from a safety monitoring committee, Sanofi also paused recruitment globally for all Phase 3 trials. Recruitment for URSA had resumed in October, ahead of Sanofi’s decision to stop the trial.