Based on positive results from the HERCULES trial, the new designation will allow for more thorough regulatory review and development of the multiple sclerosis treatment.
The FDA has granted breakthrough therapy designation to tolebrutinib (Sanofi) for the treatment of adult patients with non-relapsing secondary progressive multiple sclerosis (nrSPMS), based on positive data from the phase 3 HERCULES (NCT04411641) clinical trial, according to a news release from Sanofi.1,2
Tolebrutinib is an oral brain-penetrant Bruton tyrosine kinase inhibitor (BTKi) that achieves cerebrospinal fluid concentrations to modulate B lymphocytes and disease-associated microglia. Study results
Reduction of CDP was determined to be 31% compared with placebo (HR 0.69; 95% CI, 0.55-0.88; p=0.0026), while a further analysis of secondary end points found that the number of patients who reported an improvement in disability increased by nearly 2-fold with tolebrutinib treatment (10% with tolebrutinib compared with 5% with placebo [HR 1.88; 95% CI 1.10 to 3.21; p=0.021]).4
Among trial participants, liver enzyme elevations (>3xULN) were demonstrated in 4.1% of patients receiving tolebrutinib, compared with 1.6% in those receiving placebo. Further, 0.5% of participants in the tolebrutinib group experienced peak ALT increases of >20xULN, which all occurred within the first 90 days of treatment. Importantly, all but 1 case of liver enzyme elevation were resolved without necessitating further medical intervention.1
With the granting of this breakthrough designation, expedited review and development of tolebrutinib for this indication can be undertaken. Drugs that may qualify for this designation must demonstrate preliminary clinical evidence that the medicine can lead to substantial clinical improvements regarding significant end points over other available drugs.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 29, 2024
Patients with nrSPMS have ceased experiencing MS relapses but have continued to accumulate their disability. The condition is experienced as symptoms including fatigue, cognitive impairment, gait and balance issues, sexual dysfunction, and loss of bowel and/or bladder function, among others, according to the news release.1
“This breakthrough therapy designation demonstrates the potential for tolebrutinib to delay disability progression, a critical unmet need for people living with multiple sclerosis,” Erik Wallström, MD, PhD said in the news release.1
Peripheral B and T cells have remained the primary target of current therapies for MS. Innate immunity has been generally unaddressed in clinical trials to date. Pharmacists can play a critical role in evaluating patients for potential inclusion in clinical trials if they stand to benefit, while closely watching new treatments such as tolebrutinib as they make their way through the clinical trial pipeline. The ability to prescribe patients MS treatments that derive from innate immunity could lead to better treatment outcomes in this patient population.1,3
