The potential of Sanofi’s closely-watched BTK inhibitor in multiple sclerosis is coming into clearer view, amid plans to narrow the focus of the French company’s business drug development and get out of consumer health.
On Monday, the drugmaker said its experimental treatment tolebrutinib successfully delayed the time to disability in a Phase 3 study for patients with non-relapsing secondary progressive multiple sclerosis (nrSPMS). However, it failed to lessen relapses in two other Phase 3 trials with a wider group that included patients with relapsing forms of MS, which makes up about 85% of MS patients.
Sanofi said a pooled 6-month analysis of those two trials found a “considerable delay” in confirmed disability worsening that “supports” the finding in the nrSPMS trial, though that wasn’t the primary endpoint in those trials.
Houman AshrafianTwo years ago, the trials were placed on partial clinical hold after the FDA identified select cases of drug-induced liver damage. Sanofi R&D chief Houman Ashrafian said in an interview ahead of the data release that the company was ultimately given the okay to continue dosing new patients in the progressive MS population, and the company said in its announcement Monday that an early analysis of liver safety was “consistent with previous studies.”
Ashrafian told Endpoints News that there were “a whole bunch of patients” going through the treatment period where peak activity was expected, so he wouldn’t commit to there being no grade 4 or higher serious adverse events reported. But he said that “to date, I’ve seen nothing concerning.”
While two of the trials missing their primary endpoints of stopping relapses is certainly a negative, Ashrafian argued that slowing disability progression has a more vital real-world impact.
“Patients care about relapse because it’s irritating,” he said. “What they really care about is not being in a wheelchair.”
Sanofi and Ashrafian are hoping that regulators agree, with plans to present a data package, particularly for the progressive population, “as soon as humanly possible.” More data will also be presented at the end of September at the European Committee for Treatment and Research in Multiple Sclerosis medical meeting in Denmark.
While not a home run, the data are the most promising since tolebrutinib was acquired by Sanofi as part of its $3.7 billion buyout of Principia. The French pharma previously backed away from the drug’s potential use to treat myasthenia gravis but pressed forward in a number of multiple sclerosis indications.
Another Phase 3 readout in patients with primary progressive MS is expected to readout in 2025, which Ashrafian is confident in given that the patient population and primary endpoint are similar to the nrSPMS study.