Benefits of fenebrutinib in MS study sustained up to 2 years: Data
Treatment reduced relapses, disability progression in patients in trial extension
Almost two years of treatment with fenebrutinib — an investigational oral tablet for multiple sclerosis (MS) — helped patients with relapsing forms of the disease remain nearly free of relapses and disability progression.
That’s according to new data from the open-label extension of FENopta (NCT05119569), a Phase 2 clinical trial that tested fenebrutinib against a placebo, both taken twice daily for three months, among people with relapsing-remitting MS or active secondary progressive MS. Following the trial, participants could enter the open-label extension to receive fenebrutinib for up to 192 weeks (about 3.5 years).
“These data show that patients treated with fenebrutinib experienced an annualised relapse rate equal to one relapse every 17 years and no observed disability progression up to two years,’’ Levi Garraway, MD, PhD, Roche’s chief medical officer and head of global product development, said in a company press release. Fenebrutinib is being developed by Roche subsidiary Genentech.
The data were presented in an oral presentation, titled “Fenebrutinib Maintains Low Disease Activity in Relapsing Multiple Sclerosis: Results from the Fenopta Open-Label Extension” at The Consortium of Multiple Sclerosis Centers annual meeting in late May in Phoenix.
Number of new brain lesions reduced by 90% with treatment
Fenebrutinib works by inhibiting Bruton’s tyrosine kinase (BTK), an enzyme that activates immune cells such as B-cells and microglia. In MS, these immune cells are overly active, contributing to inflammatory damage in the brain and spinal cord. As a BTK inhibitor, fenebrutinib is expected to reduce inflammation and prevent damage.
In FENopta, three months of treatment with fenebrutinib reduced by 90% the number of new brain lesions with active inflammation on MRI scans compared with the placebo, the data showed. Of the 109 adults who started the clinical trial, 99 entered the open-label extension and 93 remained on treatment after 96 weeks (nearly two years).
Patients had an annualized relapse rate, a measure of the number of relapses adjusted to a one-year time window, of 0.06 — meaning an average of one relapse every 17 years. None experienced worsening on the Expanded Disability Status Scale (EDSS), a widely used tool to measure disability in MS.
MRI scans revealed no new T1 gadolinium-enhancing lesions, which show active inflammation in the brain. In patients who had initially received the placebo and then switched to fenebrutinib, the number of new or growing T2 lesions, which represent long-term damage, decreased from 6.72 to 0.34 by week 96.
‘Near-complete suppression’ of relapsing disease seen with fenebrutinib
Fenebrutinib was generally well tolerated, with a safety profile similar to earlier clinical trials. The most common side effects were COVID-19 (10%), urinary tract infections (10%), throat inflammation (6%), and respiratory infections (5%). Two patients experienced serious side effects, and one patient had a temporary increase in a liver enzyme, which resolved after stopping treatment.
“Participants treated with fenebrutinib for 2 years had near-complete suppression of clinical and imaging manifestations of relapsing disease,” the researchers wrote. Consistent with earlier clinical trials, “no new safety concerns were identified.”
Three fenebrutinib Phase 3 clinical trials are now underway. FENhance 1 (NCT04586010) and FENhance 2 (NCT04586023) are comparing fenebrutinib with Aubagio (teriflunomide), an approved oral therapy, in relapsing forms of MS. FENtrepid (NCT04544449) is comparing it with Ocrevus (ocrelizumab), another approved treatment, in primary progressive MS. Data are expected by the end of 2025.
Garraway noted that the therapy “is potent, highly selective, and the only reversible BTK inhibitor currently in Phase [3] trials for multiple sclerosis.”
“We look forward to seeing the first of those [trial] results later this year,” Garraway said.
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