Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that the first Phase III (FENhance 2) of two pivotal, similarly-designed Phase III studies (FENhance 1 and 2) in patients with relapsing multiple sclerosis (RMS) met its primary endpoint. Fenebrutinib, an investigational Bruton’s tyrosine kinase (BTK) inhibitor, significantly reduced the annualized relapse rate (ARR) compared to teriflunomide over a period of at least 96 weeks of treatment.
Additionally, the Phase III FENtrepid pivotal study evaluating fenebrutinib, compared with Ocrevus® (ocrelizumab) in patients with primary progressive multiple sclerosis (PPMS), met its primary endpoint. The results showed that fenebrutinib was non-inferior compared to ocrelizumab, the only approved therapy in PPMS, as measured by a delay in the onset of composite confirmed disability progression over a period of at least 120 weeks of treatment. A numerical benefit for fenebrutinib compared to ocrelizumab was seen as early as week 24, and lasted throughout the observation period.
“Fenebrutinib substantially reduced the number of relapses in RMS and slowed disability progression in PPMS. These unprecedented results suggest that fenebrutinib could potentially become a best-in-disease medicine as the first high-efficacy, oral treatment for people with RMS or PPMS,” said Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development. "Therefore, these pivotal results for fenebrutinib may offer new hope for people living with MS, and they reaffirm our enduring commitment to the MS community.”
Liver safety was consistent with previous fenebrutinib studies. Additional safety data is being further evaluated. The results of the second RMS Phase III trial (FENhance 1) are expected by the first half of 2026.
Fenebrutinib targets cells in the immune system known as B cells and microglia. Targeting B cells helps control the acute inflammation that causes relapses, while targeting microglia inside the brain addresses the chronic damage that is thought to drive long-term disability progression. Fenebrutinib, a non-covalent BTKi, is designed to have high potency, selectivity and reversibility. This design allows it to act throughout the body, and also to cross the blood-brain barrier into the central nervous system (CNS) targeting chronic inflammation.
About the FENhance 1 and 2 studies
FENhance 1 and 2 are similarly designed Phase III multicenter, randomized, double-blind, double-dummy, parallel-group studies to evaluate the efficacy and safety of investigational fenebrutinib compared with teriflunomide in a total of 1,497 adult patients with RMS. Eligible participants were randomized 1:1 to receive treatment with either oral fenebrutinib twice a day (and placebo matched to oral teriflunomide once a day) or oral teriflunomide once a day (and placebo matched to oral fenebrutinib twice a day) for at least 96 weeks.
The primary endpoint is annualized relapse rate (ARR). Key secondary endpoints include the time to onset of composite 24-week confirmed disability progression (cCDP24), 12-week confirmed disability progression (CDP12) and 24-week confirmed disability progression (CDP24).
Following the double-blind treatment period, patients have the option to enter an open-label extension (OLE) phase, in which all patients receive treatment with fenebrutinib.
About the FENtrepid study
FENtrepid is a Phase III multicenter, randomized, double-blind, double-dummy, parallel-group study to evaluate the efficacy and safety of fenebrutinib compared with Ocrevus in 985 adult patients with PPMS. Eligible participants were randomized 1:1 to receive treatment with either daily oral fenebrutinib (and placebo matched to intravenous [IV] Ocrevus) or IV Ocrevus (and placebo matched to oral fenebrutinib) for at least 120 weeks.
The primary endpoint is the time to onset of 12-week composite confirmed disability progression (cCDP12). The cCDP incorporates three measures of disability – total functional disability measured by the Expanded Disability Status Scale (EDSS), walking speed measured by the timed 25-foot walk (T25FW), and upper limb function measured by the nine-hole peg test (9HPT). This comprehensive composite endpoint offers greater sensitivity than the EDSS alone, capturing additional aspects of disability and often earlier. Key secondary endpoints include the time to onset of 24-week composite confirmed disability progression (cCDP24), 12-week confirmed disability progression (CDP12) and 24-week confirmed disability progression (CDP24).
Following the double-blind treatment period, patients have the option to enter an open-label extension (OLE) phase, in which all patients receive treatment with fenebrutinib.
https://en.wikipedia.org/wiki/Fenebrutinib
