6th September 2024
Sanofi announced that Tolebrutinib – an experimental, oral BTK-inhibitor – met the primary endpoint of delaying time to onset of confirmed disability progression in the HERCULES study among people with non-relapsing secondary progressive multiple sclerosis.* Tolebrutinib did not reach the primary endpoint of reducing relapses significantly more than a disease-modifying therapy in the two GEMINI studies in people with relapsing forms of MS.
These results were announced in a press release on September 2. Detailed results will be presented at the 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis later this month.
Background: Tolebrutinib inhibits an enzyme called “Bruton’s tyrosine kinase,” reducing the activation of B cells, which are immune cells that play a role in the response that affects the brain and spinal cord in MS. Tolebrutinib also penetrates the brain and spinal cord and regulates immune cells in the brain called microglia, which have been linked to MS progression. Tolebrutinib is one of several “BTK” inhibitors being tested in the MS pipeline.
Details:
- The primary endpoint in the HERCULES Study was time to confirmed disability progression as measured by the EDSS scale of disability progression. Tolebrutinib delayed the time to progression significantly more than inactive placebo.
- Preliminary assessment of liver safety was consistent with previous studies, according to the press release. (In June 2022, enrollment in Tolebrutinib studies was paused by the U.S. Food and Drug Administration due to some cases of liver injury that occurred in people enrolled in the trials. Most impacted participants were predisposed to liver injury and the studies continued with enhanced safety monitoring.)
- The primary endpoint in the GEMINI trials was annualized relapse rate, used to measure the average number of relapses a group of patients experience in a year. Tolebrutinib did not reduce relapses significantly more than Aubagio® (teriflunomide, Sanofi). Analysis of a secondary endpoint showed that Tolebrutinib delayed disability worsening, as measured by the EDSS scale, more than Aubagio.
- A fourth phase 3 study, the PERSEUS study, is ongoing in people with primary progressive MS. Results are expected in 2025.
*In this study, non-relapsing secondary progressive multiple sclerosis was defined as disability progression during the 12 previous months and no clinical relapses for the past 24 months.