Global Phase 3 Trials of Fenebrutinib Enrolling Relapsing and PPMS Patients

Two global Phase 3 clinical trials comparing fenebrutinib, an investigational oral BTK inhibitor by Roche, with Aubagio (teriflunomide) are now enrolling adults with relapsing forms of multiple sclerosis (MS), the National MS Society announced in a press release.

The twin studies, called FENhance 1 (NCT04586023) and FENhance 2 (NCT04586010), aim to enroll a total of 1,468 adults, ages 18 to 55, diagnosed within the last 10 years with relapsing MS, which includes relapsing-remitting (RRMS) and active secondary progressive (SPMS) disease. These trials are recruiting at sites in the U.S., Canada, Europe, Argentina, Peru, Korea, and Turkey. Contact and location information is available here and here.

A separate Phase 3 trial, called FENtrepid (NCT04544449), is enrolling up to 946 primary progressive MS (PPMS) patients, ages 18 to 65. Participants are being recruited at 70 sites worldwide — including across the U.S., Canada, and Europe — and will be randomly assigned fenebrutinib or Ocrevus (ocrelizumab) for 120 weeks (about 2.3 years).

In the FENhance studies, patients will be randomly assigned to daily treatment with either fenebrutinib plus an oral placebo matching Aubagio, or Aubagio plus an oral placebo matching fenebrutinib for 96 weeks (roughly two years).

Each trial’s main goal is to evaluate changes in patients’ annualized relapse rates and the time until disability progression, as measured by the composite 12-week confirmed disability progression.

Secondary outcomes include disability worsening sustained for at least 24 weeks, evidence of disease activity on magnetic resonance imaging (MRI) scans, and changes in physical function and cognition, as well as safety.

Participants must attend up to 20 in-person visits at their respective study sites. During these visits, they will undergo MRI scans, blood draws, clinical exams, and fill out questionnaires. Roche notes that COVID-19 precautions are in place to limit the risks inherent to in-person visits.

Upon completion of the treatment phase, patients may be eligible for an open-label extension study, during which all will be treated with fenebrutinib for up to 96 weeks.

FENtrepid also includes a placebo matched to fenebrutinib or Ocrevus, either of which will be given PPMS patients in its two treatment groups to maintain a blinded study, and in-person site visits. Its main goal is time to onset of 12-week confirmed disability progression using a composite measure. Safety, changes in total brain volume as measured on MRI scans, and patient evaluations of the disease’s physical impact are among secondary goals.

An open-label extension may follow FENtrepid, depending on benefits seen.

Fenebrutinib is an oral small molecule designed to slow MS progression by preventing certain immune cells from driving the inflammation that damages nerve cells.

The medicine is designed to enter the central nervous system (the brain and spinal cord) to block the activity of Bruton’s tyrosine kinase (BTK), an enzyme that plays a key role in activating B-cells and microglia. When activated, these cells can trigger an inflammatory immune response.