In a phase 2 study focused on multiple sclerosis (MS), Roche’s BTK inhibitor, Fenebrutinib, appears to have achieved a remarkable feat by successfully crossing the blood-brain barrier. Roche recently unveiled a major milestone in the development of its MS drug during the phase 2 FENopta study, indicating its potential as a groundbreaking treatment for the disease.
During the ECTRIMS-ACTRIMS meeting in Milan, Roche presented the results of the FENopta study, which involved 109 adults with relapsing MS. Fenebrutinib, a BTK inhibitor, demonstrated highly promising outcomes. Notably, it displayed a 90% reduction in new or enlarging gadolinium-enhancing T1 lesions, a crucial measure assessed via MRI scans at the 12-week mark, successfully meeting the primary endpoint of the trial. Moreover, the drug exhibited a remarkable 95% reduction in T2 lesions, a secondary endpoint, during the same period. Patients treated with Fenebrutinib were four times more likely to remain free from any new T1 Gd+ brain lesions or T2 brain lesions at weeks 4, 8, and 12 compared to those who received a placebo.
One standout achievement highlighted by Roche was Fenebrutinib’s ability to penetrate the blood-brain barrier, an extraordinary accomplishment in drug development. Roche measured the drug’s concentration in the cerebrospinal fluid of a subgroup of 11 patients, revealing a mean Fenebrutinib concentration of 43.1 ng/mL. This suggests that Fenebrutinib can reach levels within the brain and central nervous system that are sufficient to reduce disease activity and progression in MS patients.
Dr. Alexandra Goodyear, Roche’s global development lead for Fenebrutinib explained that affecting cells in the periphery have shown a profound impact on MS disease activity, and Fenebrutinib’s dual mechanism of action, targeting both B cells and myeloid cells, holds the potential to impact resident B cells within the central nervous system and microglia if it can penetrate the brain.
While previous trials involving BTK inhibitors have encountered challenges related to serious adverse events, Roche’s trial reported a consistent safety profile. The rate of adverse events for patients taking Fenebrutinib was 38%, compared to 33% for those on a placebo. Notably, the most common adverse event not observed in the placebo group was abnormal liver enzyme levels, affecting 5.5% of patients receiving Fenebrutinib.
Unlike competing candidates, Fenebrutinib is a non-covalent BTK molecule intentionally designed to prioritize long-term safety for patients. Nevertheless, further insights into safety will emerge from ongoing phase 3 trials. Roche is currently conducting two phase 3 studies in relapsing MS and a late-stage study in primary progressive MS, where Fenebrutinib will be compared to the renowned MS drug Ocrevus. However, significant data from these late-stage trials will not be available until later, suggesting a longer timeline for their results to become known.