In a promising development in multiple sclerosis research, tolebrutinib delayed the onset of disability progression in patients with nrSPMS.
In the HERCULES phase 3 study, tolebrutinib, an oral brain-penetrant BTK inhibitor, met the primary end point of improvement in delaying time to onset of confirmed disability progression (CDP) compared with placebo in patients with non-relapsing secondary progressive multiple sclerosis (nrSPMS), according to a news release from Sanofi.1
This trial was the first and only to show reduction in disability accumulation in nrSPMS, a condition for which there are currently no existing treatments approved and there is a large unmet health care need. In their release, Sanofi says that these results will form the basis of higher-level discussions with global regulatory agencies.1
“Tolebrutinib represents an unprecedented breakthrough as a potential first-in-disease treatment option with clinically meaningful benefit in disability accumulation,” Houman Ashrafian, MD, PhD, head of research and development at Sanofi, said in the news release. “Addressing disability accumulation, thought to be driven by smoldering neuroinflammation, remains the greatest unmet medical need in people with non-relapsing secondary progressive MS today.”1
Further results, coming from the GEMINI 1 and 2 phase 3 studies evaluating tolebrutinib, indicate the primary end point of reducing annualized relapse rate (ARR) was not met when compared with teriflunomide in patients with relapsing forms of MS. Despite this, upon examination of the key secondary end point of pooled confirmed disability worsening (CDW) data, a considerable delay in time to onset was found.1
Emma Gray, assistant director of research at the Multiple Sclerosis Society, expressed encouragement at the release of the results. “MS can be debilitating, exhausting and unpredictable and these initial results suggest that it could become a much-needed option for people who aren’t currently eligible for any disease-modifying therapies. These results increase our understanding of how drugs like tolebrutinib work and we look forward to seeing the full trial results later this year.”2
HERCULES was a randomized, double-blind trial that evaluated the safety and efficacy of tolebrutinib compared with placebo. At baseline, nrSPMS was defined as having an SPMS diagnosis with an expanded disability status scale (EDSS) score between 3.0 and 6.5, no clinical relapses across the previous 24 months, and documented evidence of disability accumulation in the prior 12 months.1
Trial Name: Nonrelapsing Secondary Progressive Multiple Sclerosis (NRSPMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) (HERCULES)
ClinicalTrials.gov ID: NCT04411641
Sponsor: Sanofi
Completion Date: August 2024
The primary target of current MS therapies to date has been peripheral B and T cells, while innate immunity—which could be a driver of disability accumulation—has remained largely unaddressed.1
The mechanism of action in tolebrutinib modulates both B lymphocytes and activated microglia in the central nervous system, which is thought to address underlying mechanisms linked to smoldering neuroinflammation in the brain and spinal cord that leads to disability accumulation in MS.1
Pharmacists play an essential role in the management of MS. Pharmacists are key in managing symptoms for patients, providing patients recommendations for addressing specific symptoms or pain. Community pharmacists can form a close relationship with their patients and can personalize their treatment using medicines that work for them.3
As these positive results put tolebrutinib on track to eventual FDA approval for patients with nrSPMS, pharmacists should educate themselves on the drug and prepare their practices for providing this drug and others for MS treatment, depending on the specific health needs of the patient.3
Disease-modifying therapies such as tolebrutinib can make a major impact in improving outcomes for patients with MS, but only if pharmacists can effectively distribute and prescribe the drug for those who need it. Above all, collaboration with a patient’s care team remains critical as tolebrutinib and other MS drugs are evaluated in clinical trials.3
Results from these trials are expected to be presented at the European Committee for Treatment and Research in Multiple Sclerosis medical meeting in September.1
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