South San Francisco, CA — November 30th, 2023 —
Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY) provides an update that the United States Food and Drug Administration (U.S. FDA) has placed the fenebrutinib multiple sclerosis (MS) clinical development program on partial clinical hold in the U.S. The action was based on two recent cases of hepatic transaminase (liver enzyme) elevations in conjunction with elevated bilirubin suggestive of drug-induced liver injury that was observed in the blinded Phase III FENhance relapsing multiple sclerosis (RMS) studies. Both patients were asymptomatic and elevations returned to normal levels following drug discontinuation.
New enrollment for the Phase III FENhance I trial (RMS) in the U.S. is paused; enrollment in countries outside of the U.S. continues. The Phase III trials FENhance II (RMS) and FENtrepid (primary progressive MS; PPMS) are fully enrolled. Participants in the U.S. who have received the study drug for more than 70 days will continue treatment in all studies. A small number of participants in the U.S. who have received the study drug for 70 days or less will discontinue treatment.
Patient safety is Genentech’s highest priority, and we are working closely with the independent data monitoring committee, and investigators around the world. To date, fenebrutinib has been studied in 2,500 people in Phase I, II and III clinical programs across multiple diseases, including MS and other autoimmune disorders. Genentech remains committed to evaluating the potential of fenebrutinib for people with RMS or PPMS.
Fenebrutinib is an investigational oral, reversible and non-covalent Bruton’s tyrosine kinase (BTK) inhibitor that blocks the function of BTK. BTK, also known as tyrosine-protein kinase BTK, is an enzyme that regulates B-cell development and activation and is also involved in the activation of innate immune system myeloid lineage cells, such as macrophages and microglia. Preclinical data have shown fenebrutinib to be potent, highly selective, and it is the only reversible inhibitor currently in Phase III trials for MS.
Fenebrutinib is a dual inhibitor of both B-cell and microglia activation. This dual inhibition may be able to reduce both MS disease activity and disability progression, thereby potentially addressing the key unmet medical need in people living with MS. The Phase III program includes two identical trials in RMS (FENhance I & II) with an active teriflunomide comparator and one trial in PPMS (FENtrepid) in which fenebrutinib is being evaluated against OCREVUS® (ocrelizumab).
About the fenebrutinib clinical development program
For an overview of the fenebrutinib clinical trial program and the impact of the FDA partial clinical hold in the U.S., please refer to the table below:
If you are a participant in this study and have questions, please reach out to the site at which you enrolled in the study.
Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.