Roche presents new 48-week data for the Bruton’s tyrosine kinase (BTK) inhibitor fenebrutinib from the phase II FENopta open-label extension (OLE) study at the ECTRIMS conference.

Results demonstrate that patients with relapsing multiple sclerosis (RMS) treated with fenebrutinib for up to one year maintained very low levels of disease activity and no disability progression.

During the OLE period, 96% of patients treated with fenebrutinib were free of relapses at one year, with an annualised relapse rate (ARR) of 0.04, and no change in disability over 48 weeks as measured by the Expanded Disability Status Scale (EDSS).

Fenebrutinib treatment suppressed disease activity in the brain as measured by MRI scans. At 48 weeks, 99% of patients were free of T1 gadolinium-enhancing (T1-Gd+) lesions, markers of active inflammation. Over the 48 weeks of OLE with continued fenebrutinib treatment, there was three times more reduction in the volume of T2 lesions, which represent chronic disease burden, compared to the end of the double-blind period (-0.33 cm3 vs. -0.11 cm3, respectively).

The safety profile of fenebrutinib in the OLE was consistent with previously reported data. The most common adverse events (AEs) in >5% of patients were urinary tract infection (8%), COVID-19 (7%) and pharyngitis (5%). Serious AEs occurred in one patient (1%). In the OLE, an asymptomatic alanine aminotransferase elevation occurred newly in one patient (1%) and resolved with treatment discontinuation.

Three Phase III clinical trials are ongoing, including the FENhance 1 and 2 trials in RMS and the FENtrepid trial in primary progressive multiple sclerosis (PPMS). Data from these studies, which will characterise the effects of fenebrutinib on disease progression across the multiple sclerosis spectrum, are expected at the end of 2025.

The FENopta study was a global Phase II, randomised, double-blind, placebo-controlled 12-week study to investigate the efficacy, safety and pharmacokinetics of fenebrutinib in 109 adults aged 18-55 years with relapsing multiple sclerosis (RMS). The primary endpoint was the total number of new T1 gadolinium-enhancing (T1-Gd+) lesions as measured by MRI scans of the brain at 4, 8 and 12 weeks. Secondary endpoints included the number of new or enlarging T2-weighted lesions as measured by MRI scans of the brain at 4, 8 and 12 weeks, and the proportion of patients free from any new T1-Gd+ lesions and new or enlarging T2-weighted lesions as measured by MRI scans of the brain at 4, 8 and 12 weeks. The goal of the FENopta study was to characterise the effect of fenebrutinib on MRI and soluble biomarkers of disease activity and progression, and it included an optional substudy to measure cerebrospinal fluid fenebrutinib levels and biomarkers of neuronal injury.

Data from the 12-week study showed that fenebrutinib is central nervous system (CNS) penetrant (crosses the blood-brain barrier) and has the potential to impact mechanisms underlying chronic progressive disease biology in multiple sclerosis patients. Fenebrutinib significantly reduced new T1-Gd+ lesions and new/enlarging T2 lesions compared to placebo. The safety profile of fenebrutinib was consistent with previous and ongoing fenebrutinib clinical trials and there were no new safety concerns identified.

Patients who completed the FENopta study were given the option to take part in an open-label extension (OLE) study, in which all patients receive fenebrutinib up to 192 weeks. Ninety-nine patients entered the OLE and 96 remained in the OLE after one year.