- The phase 3 HERCULES clinical trial examined tolebrutinib’s effectiveness in slowing disability accumulation in people with non-relapsing secondary progressive MS (nrSPMS).
- The preliminary study results show that tolebrutinib significantly delayed the time to onset of confirmed disability progression compared to placebo (mock treatment) in people with nrSPMS.
- This is the first study to date to show reduction in disability accumulation in nrSPMS.
What are Bruton’s Kinase (BTK) inhibitors?
Bruton’s tyrosine kinase (BTK) is an enzyme (a biological molecule that speeds up reactions within cells) that is important for many B cells as well as immune cells in the brain and spinal cord. Many of these cells are thought to be involved in the MS disease process and therefore BTK presents an excellent target for potentially curtailing disease progression. Unlike therapies available today, BTK inhibitors only target B cells that contain BTK and therefore do not reduce the level of all B cells. Additionally, they can cross into the brain to target immune cells within the brain tissue. Therefore, BTK inhibitors can target specific immune cells without compromising the overall immune system, offering a potentially safer and more targeted treatment to those that are currently available.
Tolebrutinib and the HERCULES clinical trial
Tolebrutinib is an experimental oral drug being studied for its ability to penetrate the brain and potentially treat non-relapsing secondary progressive MS (nrSPMS). People with nrSPMS have stopped experiencing relapses but continue to experience accumulation of disability due to their MS. Currently, there are no approved treatments for this population of people living with MS and therefore it is a significant unmet need.
In the HERCULES clinical trial, participants either received an oral daily dose of tolebrutinib or matching placebo (mock treatment) for up to 48 months. In this clinical trial, tolebrutinib delayed time to onset of confirmed disability progression in people with nrSPMS compared to people taking placebo. Preliminary analysis of liver safety was consistent with previous tolebrutinib studies.
Tolebrutinib was also tested in phase 3 clinical trials for relapsing MS (GEMINI 1 AND 2), to see if tolebrutinib reduced relapse rates compared to teriflunomide. The results showed that relapse rates were not improved in the GEMINI 1 AND 2 clinical trials. However, there was a considerable delay in disability worsening at the 6-month mark, supporting the results observed in the HERCULES clinical trial.
What does this mean for people with MS?
This is the first and only study that shows a reduction in disability accumulation in people with nrSPMS. At this stage, tolebrutinib is under clinical investigation, and its safety and effectiveness have not been evaluated by any regulatory authority. These results will serve as a foundation for future discussions with regulatory authorities. If these discussions are positive, then tolebrutinib could potentially address the unmet need for people with non-relapsing secondary progressive MS with disability progression, who have no treatment options.
Clinical trial results for HERCULES and GEMINI 1 and 2 will be presented at the upcoming European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) medical meeting this month in Copenhagen, Denmark.
Tolebrutinib is also being studied in primary progressive MS in the PERSEUS phase 3 study, where time to onset of disability worsening will also be evaluated. Results for this study are anticipated in 2025.
The commitment of researchers and trial participants remains crucial in our quest for better MS treatments and solutions for other conditions. Collaborating with industry and research institutions showcases our collective determination to positively impact the lives of those with MS.
