Sanofi’s Tolebrutinib Shows Breakthrough Potential in Slowing Disability Progression for Multiple Sclerosis Patients

Sanofi’s Tolebrutinib Shows Breakthrough Potential in Slowing Disability Progression for Multiple Sclerosis Patients

(IN BRIEF) Sanofi’s phase 3 study for its drug tolebrutinib has shown promising results in treating non-relapsing secondary progressive multiple sclerosis (nrSPMS), a condition with no current approved therapies. The HERCULES study revealed that tolebrutinib successfully delayed disability progression in nrSPMS patients, marking a significant breakthrough in MS treatment. While the drug did not meet the primary endpoint in other studies for relapsing forms of MS, it demonstrated a notable delay in disability worsening, supporting its potential use in addressing unmet needs in MS treatment. Full results will be presented at the upcoming ECTRIMS conference.

(PRESS RELEASE) PARIS, 2-Sep-2023 — /EuropaWire/ — Sanofi (EPA: SAN), a global biopharmaceutical company focused on human health, announces a major development in the treatment of multiple sclerosis (MS), with Sanofi’s tolebrutinib achieving a significant milestone in the HERCULES phase 3 study. This innovative drug is the first to demonstrate a reduction in disability accumulation for patients with non-relapsing secondary progressive multiple sclerosis (nrSPMS), a group that currently has no approved treatment options.

The HERCULES study focused on individuals with nrSPMS, a condition where patients experience a steady progression of disability without the occurrence of relapses. Tolebrutinib, an oral BTK inhibitor designed to penetrate the brain, successfully delayed the time to onset of confirmed disability progression, offering new hope for those affected by this debilitating condition.

Although tolebrutinib did not meet the primary endpoint in the GEMINI 1 and 2 studies, which evaluated its effectiveness in reducing the annualized relapse rate in relapsing forms of MS, the drug showed encouraging results in delaying disability worsening. These findings align with the positive outcomes observed in the HERCULES study, highlighting tolebrutinib’s potential in addressing the critical unmet needs in MS treatment.

Dr. Houman Ashrafian, Sanofi’s Head of Research & Development, emphasized the importance of these results, stating that tolebrutinib could represent a groundbreaking first-in-disease treatment option that addresses the smoldering neuroinflammation believed to drive disability accumulation in nrSPMS.

Sanofi plans to present the full study results at the upcoming European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) meeting in Copenhagen later this month. While tolebrutinib is still under clinical investigation and has not yet been approved by regulatory authorities, these findings mark a significant step forward in the fight against MS.

About GEMINI 1 & 2
GEMINI 1 (clinical study identifier: NCT04410978) and GEMINI 2 (NCT04410991) were randomized, double-blind phase 3 clinical studies evaluating the efficacy and safety of tolebrutinib compared to teriflunomide in participants with relapsing forms of MS. Participants were randomized in both studies (1:1) to receive either tolebrutinib and placebo daily or 14mg teriflunomide and placebo.

The primary endpoint for both studies was the annualized relapse rate for up to approximately 36 months defined as the number of confirmed adjudicated protocol defined relapses. Secondary endpoints included time to onset of confirmed disability worsening (CDW), confirmed over at least 6 months, defined as an increase of ≥1.5 points from the baseline expanded disability status scale (EDSS) score when the baseline score is 0, an increase of ≥1.0 point from the baseline EDSS score when the baseline score is 0.5 to ≤5.5 or an increase of ≥0.5 point from the baseline EDSS score when the baseline score was >5.5 in addition to the total number of new and/or enlarging T2 hyperintense lesions as detected by MRI from baseline through the end of study, the total number of Gd-enhancing T1 hyperintense lesions as detected by MRI from baseline through the end of study and the safety and tolerability of tolebrutinib.

About HERCULES
HERCULES (NCT04411641) was a randomized, double-blind phase 3 clinical study evaluating the efficacy and safety of tolebrutinib in participants with non-relapsing secondary progressive MS compared to placebo. nrSPMS was defined at baseline as having a SPMS diagnosis with an EDSS between 3.0 and 6.5, no clinical relapses for the previous 24 months and documented evidence of disability accumulation in the previous 12 months. Participants were randomized (1:1) to receive either an oral daily dose of tolebrutinib or matching placebo for up to approximately 48 months.

The primary endpoint was 6-month CDP defined as the increase of ≥1.0 point from the baseline EDSS score when the baseline score is ≤5.0, or the increase of ≥0.5 point when the baseline EDSS score was >5.0. Secondary endpoints included 3-month change in 9 hole peg test and T25-FW test, time to onset of 3-month CDP as assessed by EDSS score, total number of new or enlarging T2 hyperintense lesions as detected by MRI, change in cognitive function at the EOS compared to baseline as assessed by the Symbol Digit Modalities Test and by the California Verbal Learning Test as well as the safety and tolerability of tolebrutinib.

About tolebrutinib
Tolebrutinib is an investigational, oral, brain-penetrant, and bioactive Bruton’s tyrosine kinase (BTK) inhibitor that achieves CSF concentrations predicted to modulate B lymphocytes and disease-associated microglia. Tolebrutinib is being evaluated in phase 3 clinical studies for the treatment of various forms of multiple sclerosis and its safety and efficacy have not been evaluated by any regulatory authority worldwide. For more information on tolebrutinib clinical studies, please visit www.clinicaltrials.gov.

About Sanofi
We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people’s lives. Our team, across the world, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the center of our ambitions.
Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY

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SOURCE: Sanofi