• Fenebrutinib cut relapses by 51% and 58% vs teriflunomide in Phase III RMS trials (FENhance 1 & 2) while showing a consistent, positive trend in delaying disability
• Fenebrutinib became the first investigational medicine in more than a decade to slow disability progression in a Phase III PPMS trial (FENtrepid), with numerical benefit vs Ocrevus
• Fenebrutinib is designed to address two drivers of MS – acute inflammation causing relapses and chronic brain inflammation driving disability progression
• If approved, fenebrutinib would become the first BTK inhibitor and first high-efficacy oral treatment for both RMS and PPMS, offering a new option for the nearly 1 million Americans living with MS

Genentech, a member of the Roche Group (SIX: RO, ROP; OTCQX: RHHBY), announced that the U.S. Food and Drug Administration (FDA) has accepted the company’s New Drug Application (NDA) under priority review for fenebrutinib, an investigational non-covalent Bruton’s tyrosine kinase (BTK) inhibitor for the treatment of relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS). The filing acceptance is based on data from the comprehensive clinical program, including the Phase III FENhance 1 and 2 RMS studies and the Phase III FENtrepid PPMS study.

"People living with multiple sclerosis need treatments that go beyond controlling relapses to help preserve function and independence as the disease progresses," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "Three Phase III studies have demonstrated the potential for fenebrutinib to address both relapsing and progressive disease, thereby bringing us closer to an oral treatment that could make a meaningful difference across the MS spectrum."

“Ocrevus transformed how we treat MS, helping more than 525,000 people live a life less defined by their disease. Yet, over a third of all people with MS still receive lower-efficacy treatment,” said Teresa Graham, Chief Executive Officer, Pharma. “If approved, fenebrutinib could open a new chapter as the first high-efficacy oral therapy for both relapsing and primary progressive MS, helping to control disease activity while giving people more flexibility and choice.”

Concurrently addressing the life-disrupting relapses and long-term disease progression – the slow, steady loss of physical and mental abilities over time – remains one of the greatest challenges in MS. Fenebrutinib is designed to act throughout the body and to cross the blood-brain barrier into the central nervous system to target both the acute inflammation that causes relapses and the chronic inflammation that is thought to drive disability progression.

The NDA for fenebrutinib is supported by three positive Phase III studies:

• The FENhance 1 and 2 RMS studies showed that fenebrutinib significantly reduced relapses and both active and chronic brain lesions compared with standard of care, teriflunomide. Fenebrutinib reduced the annualized relapse rate (ARR) by 51.1% (p<0.001) in FENhance 1 and 58.5% (p<0.00001) in FENhance 2 compared with teriflunomide over 96 weeks. This equates to patients having approximately one relapse every 17 years, which is the lowest relapse rate seen in Phase III MS studies. In addition, measures of disability progression, including 12-week composite confirmed disability progression (cCDP12), showed consistent positive trends favoring fenebrutinib over teriflunomide.
• The FENtrepid PPMS study showed fenebrutinib met its primary endpoint of non-inferiority compared with Ocrevus^® (ocrelizumab), the current standard of care and only approved medicine for PPMS, in reducing disability progression. Fenebrutinib numerically reduced the risk of progression by 12% compared to Ocrevus, as measured by the time to onset of cCDP12 (hazard ratio [HR] 0.88; 95% confidence interval [CI]: 0.75, 1.03), with curves separating as early as 24 weeks. A consistent treatment effect on disability progression was observed across patient subgroups, including those without active inflammation, and for the entire treatment duration after 24 weeks.

The overall rate of serious adverse events for fenebrutinib and teriflunomide, respectively, was 9% and 9% in FENhance 1 and 11% and 6% in FENhance 2. The overall rate of serious adverse events in FENtrepid was 19% for fenebrutinib and 19% for Ocrevus. Liver enzyme elevations were comparable between the fenebrutinib and teriflunomide arms in the RMS studies and observed more often with fenebrutinib compared to Ocrevus in the PPMS study. While an imbalance in reported fatalities was observed across the three pivotal studies, the deaths occurred at different timepoints and had various causes. Overall, fenebrutinib has shown a manageable safety profile across the three Phase III and earlier studies, with a large safety database including more than 2,700 study participants.