Fenebrutinib Found Effective in Suppressing Relapsing Multiple Sclerosis Disease Activity

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Forty-eight week data from the Phase II FENopta open-label extension (OLE) study demonstrated that fenebrutinib, Roche’s investigational Bruton’s tyrosine kinase (BTK) inhibitor, effectively suppressed disease activity and halted disability progression in patients with relapsing multiple sclerosis (RMS). According to the company, patients treated with fenebrutinib for up to one year maintained very low levels of disease activity and no disability progression.¹

“After a year of treatment, our BTK inhibitor fenebrutinib was able to suppress nearly all disease activity and disability progression in people with multiple sclerosis,” said Levi Garraway, MD, PhD, chief medical officer, head, global product development, Roche, in a press release. “If these results are validated in the ongoing Phase III trials, fenebrutinib could further advance the treatment landscape for people living with multiple sclerosis.”

Fenebrutinib was designed to block the function of BTK, which is an enzyme that regulates B-cell development and activation and is also a part of the activation of innate immune system myeloid lineage cells, including macrophages and microglia. Roche stated that the drug has been found 130 times more selective for BTK compared to other kinases.

The global Phase II, randomized, double-blind, placebo-controlled 12-week FENopta study investigated the efficacy, safety, and pharmacokinetics of fenebrutinib in 109 adults aged 18-55 years with RMS. The primary endpoint of the study was the total number of new T1 gadolinium-enhancing (T1-Gd+) lesions as measured by MRI scans of the brain at four, eight, and 12 weeks. Secondary endpoints included the number of new or enlarging T2-weighted lesions as measured by MRI scans of the brain at four, eight, and 12 weeks, and the proportion of patients free from any new T1-Gd+ lesions and new or enlarging T2-weighted lesions as measured by MRI scans of the brain at four, eight, and 12 weeks.

After one year of treatment, 96% of patients experienced no relapses, with an annualized relapse rate of just 0.04, and no progression in disability according to the Expanded Disability Status Scale. Additionally, 99% of patients were free of T1-Gd+lesions at 48 weeks. During the 48 week OLE with continued fenebrutinib treatment, there was a three times greater reduction in the volume of T2 lesions, which represent chronic disease burden, compared to the end of the double-blind period.

Fenebrutinib’s safety profile remained consistent, with only mild adverse events (AEs) reported, including urinary tract infection, COVID-19, and pharyngitis. Only one patient experienced a serious AE, while a patient in the OLE experienced elevated asymptomatic alanine aminotransferase.¹

According to the National Multiple Sclerosis Society (NMSS), around 85% of people with MS are diagnosed with relapsing-remitting MS, making it the most common form of the disease.2 In the United States, an estimated one million people have been diagnosed with MS, while around 2.3 million people worldwide have been diagnosed with the disease.

Last year, NMSS funded an analysis of available information to determine the disease’s prevalence among adults in the United States. Results found that the prevalence was increasing due to people living longer and improvements in diagnosis. Full data from FENtrepid as well as FENhance 1 and 2 trials in RMS are expected by the end of next year, with Phase III clinical trials in progress.¹

References

1. Roche’s fenebrutinib demonstrated near-complete suppression of disease activity and disability progression for up to 48 weeks in patients with relapsing multiple sclerosis. Roche. September 4, 2024. Accessed September 6, 2024. https://www.roche.com/media/releases/med-cor-2024-09-04

2. Relapsing-Remitting Multiple Sclerosis (RRMS). NMSS. Accessed September 6, 2024. https://www.nationalmssociety.org/understanding-ms/what-is-ms/types-of-ms/relapse-remitting-ms#:~:text=Approximately%2085%25%20of%20people%20with%20MS%20are%20initially%20diagnosed%20with%20RRMS.

3. MS Prevalence. NMSS. Accessed September 6, 2024. https://www.nationalmssociety.org/about-the-society/who-we-are/research-we-fund/ms-prevalence#:~:text=Prevalence%20of%20MS,in%20the%20world%20have%20MS.