The company was expecting a decision from the FDA by Sept. 28 for its oral drug tolebrutinib, but an update to the drug’s application package convinced the agency to take more time to review.
The FDA review for Sanofi’s oral, brain-penetrating Bruton’s tyrosine kinase inhibitor tolebrutinib will take a little longer than expected as the agency kicked its expected decision from Sept. 28 to Dec. 28, according to an announcement from the company on Monday.
During the review for tolebrutinib to treat non-relapsing, secondary progressive multiple sclerosis (nrSPMS), Sanofi submitted additional data that the FDA said constitutes a major amendment to the new drug application (NDA). The agency therefore extended the time needed to review the full package.
The ongoing review is based on a handful of clinical studies, including the Phase III trials HERCULES, GEMINI 1 and GEMINI 2.
Sanofi did not reveal the nature of the new analyses submitted to the FDA. Analysts at Leerink Partners speculated that the FDA might be waiting for additional safety data from another Phase III trial, called PERSEUS, testing the drug in primary multiple sclerosis and expected to wrap up in November.
All trials testing the drug were paused in 2022 due to multiple cases of drug-induced liver injury. Sanofi CEO Paul Hudson has noted the possibility that weekly liver monitoring will be required during the first 90 days of treatment with tolebrutinib. This “could constrain commercial adoption,” Leerink wrote.
That testing “seems very sensible to us,” Hudson said at a Sept. 10 investor conference, according to Leerink. “It was a choice that we made to go to weekly monitoring if something was manageable for patients. We know where there were some cases of elevated liver that were picked up in the monitoring within the week that returned to normal.”
Safety hasn’t been the only speed bump for tolebrutinib on the road to the FDA. Once the trials resumed following the 2022 hold, the drug missed the primary efficacy endpoints in both GEMINI 1 and GEMINI 2, unable to significantly improve relapse rates in patients with relapsing MS. In HERCULES, however, the drug did hit significance, delaying disability progression in patients with nrSPMS.
Tolebrutinib snagged the FDA’s breakthrough therapy designation in December 2024 on the heels of data from the successful HERCULES study. The drug came to Sanofi through the 2020 acquisition of Principia Biopharma for $3.7 billion.
