In the Phase 2 study, which met its primary and secondary endpoints, Roche’s investigational, potent and highly selective oral Bruton’s tyrosine kinase (BTK) inhibitor fenebrutinib significantly reduced the brain lesions compared to placebo


Roche Diagnostics administration and R&D buildings. (Credit: F. Hoffmann-La Roche Ltd)

Swiss pharmaceutical firm Roche has unveiled positive results for its new drug, fenebrutinib, in treating adults with relapsing multiple sclerosis (RMS), from the Phase 2 FENopta study.

Fenebrutinib is an experimental, oral, reversible, and non-covalent Bruton’s tyrosine kinase (BTK) inhibitor that works to block the activity of BTK.

BTK is an enzyme that regulates B-cell development and activation and is involved in the activation of innate immune system myeloid lineage cells, such as macrophages and microglia.

FENopta is a Phase 2, randomised, double-blind, placebo-controlled study that evaluated the efficacy, safety, and pharmacokinetics of fenebrutinib in 109 RMS patients, aged 18-55 years.

The Phase 2 study met its primary and secondary endpoints and showed that the drug significantly reduced MRI markers of MS disease activity in the brain compared to the placebo.

The primary endpoint is the total number of new gadolinium-enhancing T1 lesions in the brain, as measured by MRI scans at four, eight and 12 weeks.

Secondary endpoints include the number of new or enlarging T2-weighted lesions as measured by MRI scans of the brain at four, eight and 12 weeks.

It also includes the proportion of patients free from any new gadolinium-enhancing T1 lesions and new or enlarging T2-weighted lesions at four, eight and 12 weeks.

Roche chief medical officer and global product development head Levi Garraway said: “I am encouraged by this clinical data for fenebrutinib, which is important news for people living with MS.

“Fenebrutinib’s mechanism of action which can inhibit both B cells and microglia, has the potential to both reduce MS disease activity, such as relapses, and also impact disease progression.”

Fenebrutinib is a dual inhibitor of both B-cell and microglia activation, which can reduce both MS disease activity and progression, to address a key unmet medical need in people living with MS.

According to the data from the pre-clinical studies, fenebrutinib is shown to be a potent, highly selective, and the only reversible inhibitor currently in Phase 3 development for MS.

The Phase 3 programme includes two identical clinical trials in RMS, FENhance 1 and 2, with an active teriflunomide comparator.

It also includes a clinical trial in primary progressive MS (PPMS), dubbed FENtrepid, which evaluates fenebrutinib against Ocrevus (ocrelizumab).

Currently, the Swiss drugmaker’s Phase 3 fenebrutinib clinical trial programme in RMS and primary progressive MS (PPMS) is ongoing.