Genentech, part of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), is making headway in the race to develop new treatments for multiple sclerosis (MS). The company’s investigational drug, fenebrutinib, continues to deliver encouraging results for people with relapsing forms of MS, according to new data from a 96-week study presented at the Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting in Phoenix, Arizona.
The latest results come from the open-label extension (OLE) of the Phase II FENopta study, where 99 patients with relapsing MS were given fenebrutinib. After nearly two years, 93 participants remained in the study, and the data is striking: patients had an annualized relapse rate (ARR) of just 0.06, which works out to roughly one relapse every 17 years. Even more notably, none of the patients experienced disability progression during this period, as measured by the Expanded Disability Status Scale (EDSS).
MRI scans supported these clinical findings. After 96 weeks, no new T1 gadolinium-enhancing lesions, which indicate active inflammation, were detected in patients on fenebrutinib. For those who switched from placebo to fenebrutinib, the annualized rate of new or enlarging T2 lesions, a marker of chronic disease burden, dropped from 6.72 at the end of the initial 12-week double-blind period to just 0.34 by the end of the OLE.
Safety is always a concern with new therapies, but fenebrutinib’s profile remains consistent with earlier studies. The most common adverse events were COVID-19 and urinary tract infections (10% each), pharyngitis (6%), and respiratory tract infection (5%). Serious adverse events were rare, occurring in just two patients (2%). One patient experienced an asymptomatic elevation in liver enzymes, which resolved after discontinuing the drug.
Fenebrutinib is an oral, reversible Bruton’s tyrosine kinase (BTK) inhibitor. Unlike other BTK inhibitors, it is both potent and highly selective, and it’s currently the only reversible BTK inhibitor in Phase III trials for MS. The drug works by blocking BTK, an enzyme involved in the activation of B-cells and innate immune cells like macrophages and microglia. This dual action may help reduce both disease activity and disability progression, a key gap in current MS treatments.
Preclinical data indicate that fenebrutinib is 130 times more selective for BTK compared to other kinases, which could translate into fewer off-target effects. The drug’s ability to cross the blood-brain barrier is particularly important for MS, a disease that attacks the central nervous system.1
Genentech is not stopping here. Three Phase III trials are ongoing: FENhance 1 and 2, which compare fenebrutinib to teriflunomide in relapsing MS, and FENtrepid, which is the only trial evaluating a BTK inhibitor against Ocrevus in primary progressive MS. The first results from these studies are expected at the end of 2025. To date, more than 2,700 patients and healthy volunteers have received fenebrutinib across various clinical programs, including MS and other autoimmune disorders.
Multiple sclerosis affects more than 2.9 million people worldwide and is the leading cause of acquired non-traumatic disability in young adults. Most patients are diagnosed with relapsing-remitting MS (RRMS), but many eventually develop secondary progressive MS, which is marked by steadily worsening disability. Primary progressive MS, a less common but more debilitating form, has had limited treatment options until recently.
The ultimate goal in MS care is to slow or stop progression as early as possible. Fenebrutinib’s dual mechanism and early results suggest it could help fill this need, but the upcoming Phase III data will be crucial in determining its place in the treatment landscape.
