Sanofi's BTK inhibitor tolebrutinib promising in phase 3 MS study

Sanofi has announced encouraging results from a phase 3 study involving its investigational BTK inhibitor, tolebrutinib, aimed at patients with non-relapsing secondary progressive multiple sclerosis (nrSPMS). These findings are expected to be pivotal for future discussions with global regulatory authorities.

The phase 3 HERCULES trial has been evaluating the efficacy of an oral dose of tolebrutinib compared to a placebo in multiple sclerosis (MS) patients who have ceased experiencing confirmed relapses but continue to face accumulating disabilities. Tolebrutinib successfully met the primary endpoint by demonstrating an improvement over the placebo in delaying the time to onset of confirmed disability progression. According to Sanofi, tolebrutinib is now the first and only drug to show a reduction in disability accumulation for this specific patient group.

Despite these promising results, Sanofi reported that tolebrutinib did not achieve the primary endpoint in two other phase 3 trials, GEMINI 1 and 2, which focused on relapsing forms of MS. These trials aimed to compare the drug's ability to reduce the annualized relapse rate against Sanofi’s current oral MS therapy, Aubagio (teriflunomide). Analysis of six-month data from the GEMINI studies indicated a “considerable delay” in onset time, but the primary endpoint was not met.

Multiple sclerosis affects approximately 2.9 million people globally. The disease occurs when the immune system attacks the protective myelin sheath covering the nerves, leading to impaired communication between the brain and the rest of the body. Relapsing MS, which involves periods of worsening neurological function followed by partial or complete recovery, accounts for about 85% of initial diagnoses. In contrast, nrSPMS is less common.

Houman Ashrafian, head of research and development at Sanofi, emphasized the significance of tolebrutinib’s trial results, stating that it represents a groundbreaking potential treatment option that offers a clinically meaningful benefit in slowing disability accumulation. Ashrafian highlighted that addressing disability accumulation, believed to be driven by smouldering neuroinflammation, remains a critical unmet medical need for people with nrSPMS.

These results come on the heels of Sanofi’s positive outcomes from a mid-stage study on another investigational drug, frexalimab, a CD40L monoclonal antibody. Frexalimab has shown significant benefits in relapsing MS and nrSPMS during its phase 3 development. After one year of treatment, frexalimab exhibited a considerable reduction in plasma levels of neurofilament light chain, a vital biomarker associated with nerve cell damage in MS.

In summary, Sanofi's phase 3 HERCULES trial results for tolebrutinib are promising, suggesting potential advancements in treating non-relapsing secondary progressive multiple sclerosis by delaying disability progression. While the GEMINI trials for relapsing MS forms did not meet their primary endpoints, the continued research in this field underscores the importance of developing effective treatments for different MS stages. These findings are likely to inform future regulatory discussions and pave the way for new therapeutic options for MS patients worldwide.