Sanofi’s experimental drug for multiple sclerosis (MS) has been hit with another US regulatory delay, a setback compounded by disappointing results from a Phase III trial that were announced simultaneously.
The US Food and Drug Administration (FDA) has pushed back the review of tolebrutinib in non-relapsing secondary progressive multiple sclerosis (nrSPMS) to the end of Q1 2026. Sanofi had initially been awarded a US target action date of 28 December 2025.
Share price in the French drugmaker fell 6% to €78.40 ($92.08) at market open on 15 December, compared to a market close of €83.32 on 12 December. The pharma company has a market cap of €98.3bn.
Sanofi stated that it had submitted an expanded access protocol for tolebrutinib in nrSPMS, upon the agency’s request. Expanded access is a pathway for patients with serious or immediately life-threatening diseases to access an investigational drug without needing to be enrolled in a clinical trial.
Nearly one million individuals are living with MS in the US, as per the latest data available from 2019. nrSPMS is a form of the neurological disease where disability steadily worsens without relapses.
This marks the second delay for tolebrutinib in 2025. Sanofi had originally anticipated a decision on the Bruton's tyrosine kinase (BTK) inhibitor by the end of September, but additional analyses submitted to the agency pushed the decision date back to December.
Compounding the delay, Sanofi also revealed that tolebrutinib failed a Phase III trial that was evaluating the drug as a treatment for primary progressive multiple sclerosis (PPMS). PPMS accounts for around 10%-15% of diagnoses of the overall MS population.
Results from the PERSEUS study (NCT04458051) demonstrated that tolebrutinib did not meet its primary endpoint in delaying time to six-month composite confirmed disability progression (cCDP) in PPMS patients.
"We are disappointed by today’s results; however, we do believe that these results will improve our understanding of the underlying disease biology of MS,” said Houman Ashrafian, executive vice president, head of R&D at Sanofi. Based on this, Sanofi will no longer seek regulatory registration for the drug in PPMS.
The double regulatory delay and trial disappointment mark the latest difficulties in a tumultuous development journey for tolebrutinib, an asset acquired as part of Sanofi’s $3.7bn takeover of Principia Biopharma in 2021. Despite boasting breakthrough therapy designation, the drug has faced challenges in the clinic. In September 2024, it failed two of three Phase III trials in MS patients, which ultimately forced Sanofi to focus on the nrSPMS indication.
Three years ago, the FDA placed a partial hold on further enrollment in certain tolebrutinib trials due to drug-induced liver injury in patients. In announcing the PERSEUS results, Sanofi said that drug-induced liver injury remains an identified risk of the therapy.
Analysis by GlobalData forecasts that tolebrutinib sales could reach global sales of $1.4bn by 2031 if approved, entering blockbuster territory the year prior.
GlobalData is the parent company of Clinical Trials Arena.
