Progressive MS Patients Urged to Enroll in Phase 3 Trials of Tolebrutinib

Investigators are looking for people with progressive forms of multiple sclerosis (MS) to participate in two Phase 3 clinical trials assessing the safety and effectiveness of tolebrutinib (SAR442168), an oral BTK inhibitor that is being investigated as a potential treatment, the National Multiple Sclerosis Society announced in a press release.

Both studies — HERCULES (NCT04411641) and PERSEUS (NCT04458051) — are being sponsored by Sanofi Genzyme, the company that holds tolebrutinib’s commercial rights. The trials are recruiting participants at several locations across the U.S., Europe, and Canada.

The studies intend to recruit about 2,280 adult patients, including 990 (ages 18–55) with primary progressive MS to be enrolled in PERSEUS, and 1,290 with non-relapsing secondary progressive MS (ages 18–60) to be enrolled in HERCULES.

Discovered originally by Principia Biopharma, tolebrutinib is an oral small selective inhibitor of the enzyme Bruton tyrosine kinase (BTK), which is important for the activity and survival of antibody-producing B-cells. These immune cells are thought to be one of the key drivers of brain and spinal cord inflammation in MS patients.

By lowering BTK activity, tolebrutinib is expected to reduce B-cells’ activity and reduce inflammation associated with MS. In addition to those effects on B-cells, the experimental therapy also is thought to inhibit the activity of microglia (the immune cells of the brain), which has been linked to MS progression.

HERCULES and PERSEUS are both double-blind, randomized, placebo-controlled studies designed to compare the safety and effectiveness of tolebrutinib to that of a placebo, when given once daily for 24–48 months (two to four years).

The main goal of both trials is to assess if tolebrutinib might be superior to a placebo at delaying patients’ disability progression, as measured by the expanded disability status scale (EDSS). Additional study goals include assessing the therapy’s safety, as well as its effects on patients’ walking speed, cognitive function, quality of life, and disease activity.

Patients enrolled in both trials will need to visit their nearest study site up to 16 times. They will undergo several clinical exams, including standard blood tests and brain MRI scans, and will complete multiple questionnaires over the course of the studies.

Importantly, since in-person visits will be required in these trials, investigators and other staff at each site will take all necessary safety precautions to reduce the risk of participants’ exposure to COVID-19.

Those who wish to know more information about the studies, including their eligibility to enroll, may contact Sanofi by email at [email protected], or by phone at 800-633-1610 (extension option six).

Of note, two other Phase 3 clinical trials — GEMINI 1 (NCT04410978) and GEMINI 2 (NCT04410991) — comparing tolebrutinib with the approved MS therapy Aubagio, also marketed by Sanofi, are currently enrolling people with relapsing MS, which includes relapsing-remitting MS and active secondary progressive MS.