
BTK Inhibitor Fenebrutinib Demonstrates Long-Term Suppression of MS Activity in Open-Label Extension
Key Takeaways
- Fenebrutinib demonstrated low relapse rates and no disability progression in RMS patients over two years, with no new active brain lesions observed.
- The drug is a reversible dual inhibitor of B-cell and microglia activation, currently in phase 3 trials for both relapsing and primary progressive MS.
Fenebrutinib shows promising results in reducing relapse rates and disability progression in relapsing multiple sclerosis patients over two years.
Newly presented results from the open-label extension (OLE) of the phase 2 FENopta study (NCT05119569) showed that patients with relapsing multiple sclerosis (RMS) on fenebrutinib (Genentech) had low relapse rates with no active brain lesions or disability progression after 2 years of treatment. Phase 3 studies assessing the investigational Bruton tyrosine kinase (BTK) inhibitor in relapsing and primary progressive MS are expected to start reading out at year end.1
The data, unveiled at the
"These data show that patients treated with fenebrutinib experienced an annualized relapse rate equal to one relapse every 17 years and no observed disability progression up to two years," Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Genentech, said in a statement. "Fenebrutinib is potent, highly selective and the only reversible BTK inhibitor currently in Phase III trials for multiple sclerosis, and we look forward to seeing the first of those results later this year."
Fenebrutinib remains the only reversible dual inhibitor of both B-cell and microglia activation currently in development for MS. In addition to FENopta, the medication is being tested in the phase 3 FENhance 1 (NCT04586023) and 2 (NCT045586010) trials of RMS, as well as the FENtrepid trial (NCT04544449) of primary progressive MS.
In the latest 96-week data, there were no reports of new T1 gadolinium-enhancing lesions, markers of active inflammation, and a safety profile that was consistent with previous reports. Among those who switched from placebo to fenebrutinib in the OLE, the annualized rate of new or enlarging T2 lesions decreased from 6.72 at the end of the 12-week double-blind period to 0.34 by 96 weeks.
Among fenebrutinib-treated patients, the most common adverse events (AEs) were COVID-19 (10%), urinary tract infection (10%), pharyngitis (6%), and respiratory tract infection (5%). Serious AEs occurred in 2% of patients, including 1 case of asymptomatic ALT elevation at OLE week 4 (after 16 weeks of treatment), which resolved after discontinuation.
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In the double-blind portion of FENopta,
The clinical community eagerly awaits the results from FENtrepid, a study of fenebrutinib in primary progressive MS, later this year. This double-blind, double-dummy, parallel-group trial includes 946 patients aged 18 to 65 years who are randomly assigned 1:1 to either fenebrutinib or placebo or intravenous ocrelizumab (Ocrevus; Genentech), the first and only approved therapy for progressive MS, for 120 weeks. An OLE may follow FENtrepid, depending on the observed benefits.
In November 2023, the
REFERENCES
1. Genentech’s Fenebrutinib Maintains Near-Complete Suppression of Disease Activity and Disability Progression for up to Two Years in People With Relapsing Multiple Sclerosis. News release. Genentech. May 29, 2025. Accessed May 30, 2025. https://www.gene.com/media/press-releases/15064/2025-05-29/genentechs-fenebrutinib-maintains-near-c
2. Genentech’s BTK inhibitor fenebrutinib significantly reduced brain lesions in people with relapsing forms of multiple sclerosis. News release. May 17, 2023. Accessed May 30, 2025. https://www.businesswire.com/news/home/20230516005196/en/Genentech%E2%80%99s-BTK-Inhibitor-Fenebrutinib-Significantly-Reduced-Brain-Lesions-in-People-With-Relapsing-Forms-of-Multiple-Sclerosis
3. Fenebrutinib multiple sclerosis clinical trial program update. News release. Genentech/Roche. November 30, 2023. Accessed May 30, 2025. https://www.gene.com/media/statements/ps_113023
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