Fenebrutinib Suppresses and Disability Progression in Majority of MS Patients in Extension Study

A number of drugmakers are racing to win the first FDA approval of a Bruton’s kinase (BTK) inhibitor to treat multiple sclerosis (MS). Roche showed it is in the thick of the competition with an announcement of positive results for its BTK candidate, fenebrutinib. In an open-label extension of the phase 2 FENopta study. According to the company's announcement, 96% of participants who received fenebrutinib had no relapses after one year and no change in Expanded Disability Status Scale (EDSS) score over 48 weeks. The overall annualized relapse rate was 0.04.

Furthermore, MRI scans showed that 99% of patients had no new T1 lesions, a measure of active inflammation, according to the Roche news release. T2 lesions, which indicate chronic disease burden, were reduced by three times during the 48-week open-label period compared to the end of the blinded trial. The safety profile was comparable to previously reported results, with the most common adverse effects being urinary tract infection, COVID-19 and pharyngitis.

The FENopta study randomized 109 adults ages 18 to 55 years with relapsing forms of MS to receive oral fenebrutinib or placebo twice daily for 12 weeks. After the three-month period, 99 participants chose to enroll in the open-label extension study, in which all participants will continue to receive daily fenebrutinib for up to three and a half years.

Roche is scheduled to present data from the extension study at the 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Copenhagen, Denmark, on September 18, 2024.

Fenebrutinib is an investigational oral, noncovalent (reversible) BTK inhibitor being developed by Genentech, a Roche subsidiary, for treating relapsing forms of MS and primary progressive MS (PPMS). In preclinical studies, fenebrutinib demonstrated 130 times more selectivity for BTK versus other kinases, a feature that, along with its reversibility, that Roche claims may help reduce off-target drug effects and potentially contribute to a favorable safety profile for fenebrutinib.

The investigational molecule is currently in three phase 3 trials for the potential treatment of various forms of MS. The FENhance and FENhance 2 trials are evaluating the use of fenebrutinib compared with Sanofi’s Aubagio (teriflunomide) in adults with relapsing forms of MS. The FENtrepid trial compares fenebrutinib with Roche’s Ocrevus (ocrelizumab) in adults with PPMS.

Other investigational BTK inhibitors in phase 3 studies for treating MS include Sanofi’s tolebrutinib, Merck KGaA’s evobrutinib, and Novartis’ remibrutinib. Trials for the four agents had previously been slammed by the FDA with patrial clinical holds because of problems with liver toxicity.