Sanofi’s multiple sclerosis drug fails in key trials

The French pharmaceutical giant Sanofi’s most advanced multiple sclerosis (MS) drug candidate, tolebrutinib, has failed to meet the primary endpoint in two Phase III trials for relapsing forms of the disease, casting doubts on the future of this class of treatments. 
Sanofi has revealed that the experimental daily pill did not surpass its existing MS medication, Aubagio, in reducing relapse rates for common relapsing forms of MS, which are characterized by intermittent flare-ups followed by periods of remission.
However, there was a silver lining for Sanofi: a separate third Phase III trial showed that tolebrutinib achieved its primary goal in treating a progressive form of MS, a condition marked by a steady worsening of symptoms and a current lack of effective treatments. In this trial, tolebrutinib demonstrated a slower progression of disability compared to a placebo.
Houman Ashrafian, Sanofi’s Head of Research & Development, described tolebrutinib as an “unprecedented breakthrough” with the potential to significantly impact the management of disability accumulation. The company intends to discuss these findings with regulatory authorities and aims to file for approval by the end of 2024.
Sanofi is diversifying its MS treatment portfolio to offset revenue losses from the expiration of Aubagio’s patent. This effort is part of a broader strategy to strengthen its position in the anti-inflammatory treatment market. 
CEO Paul Hudson has been striving to rebuild investor confidence in the company’s pipeline since abandoning 2025 margin targets last October to increase investment in drug development. Recent drug launches, including Beyfortus for respiratory infections, have contributed to a boost in the company’s stock.
Tolebrutinib, which Sanofi acquired through its $3.7 billion purchase of Principia Biopharma in 2020, is a Bruton’s tyrosine kinase (BTK) inhibitor. This class of drugs is designed to offer a more targeted approach to MS treatment by selectively blocking harmful autoimmune reactions that contribute to the disease. 
Despite its promise, the drug has faced scrutiny over concerns about liver damage and uncertain efficacy. In 2022, new patient enrolment in three of Sanofi’s tolebrutinib studies was halted due to liver safety issues. The company has stated that liver safety data remains consistent with previous findings, with further details expected to be released on 20th September.
Other BTK inhibitors from competitors like Merck KGaA and Roche have also encountered difficulties. Merck KGaA’s BTK inhibitor failed to meet its efficacy goal in MS trials last December, while Roche’s candidate has faced safety concerns. Novartis, however, has reported that its BTK drug candidate showed no signs of liver damage.
Sanofi is set to present more detailed results from the two relapsing-MS trials, GEMINI I & II, and the progressive MS trial, HERCULES, at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) conference in Copenhagen on 20th September. An additional Phase III study, PERSEUS, which is investigating another progressive form of MS, is still ongoing, with results expected in 2025.