Fenebrutinib linked to reduced lesion activity, higher CSF penetration in MS at 12 weeks
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Key takeaways:
- Fenebrutinib is a highly selective, noncovalent, reversible Bruton’s tyrose kinase inhibitor.
- Treatment with fenebrutinib led to reduction of new lesion activity and higher CSF penetration in patients with MS.
In relapsing forms of multiple sclerosis, fenebrutinib treatment led to reduction of lesion activity and resulted in higher penetration into cerebrospinal fluid at 12 weeks, according to research from ECTRIMS 2023.
“Rapidly acting therapies are needed for multiple sclerosis that can control both the acute inflammation that underlies relapses and the chronic inflammation that is involved in non-relapsing progressive disease,” Amit Bar-Or, MD, FRCP, FAAN, FANA, director of the Center for Neuroinflammation and Neurotherapeutics at the University of Pennsylvania Perelman School of Medicine, and colleagues wrote. “Bruton’s tyrosine kinase is a key enzyme linked to both inflammatory components in MS, and fenebrutinib is a potent, highly selective, noncovalent, reversible BTK inhibitor.”
Bar-Or and fellow researchers sought to assess the ability of fenebrutinib to penetrate cerebrospinal fluid and to evaluate its early effects on lesion activity from the ongoing phase 2 FENopta study.
They included 106 individuals with relapsing MS, who were randomized 2:1 to receive either 200 mg twice per day of fenebrutinib or placebo for 12 weeks. Presence of new gadolinium-enhancing (Gd+) lesions, new/enlarging T2 (NET2) lesions, and new T1 hypointense lesions were assessed at weeks 4, 8 and 12, while levels of the drug were measured in lumbar puncture cerebrospinal fluid samples 12 weeks after drug administration in a subset of study participants and compared with those obtained in standard potency assays.
Results showed those in the treatment group demonstrated a 90% relative reduction in new Gd+ lesions and a 95% relative reduction in NET2 lesions compared with those given placebo at week 12.
Researchers also found proportions of participants receiving fenebrutinib compared with participants receiving placebo with new Gd+ lesions from baseline through weeks 4, 8 and 12 were 18.6% vs. 22.2%; 19.4% vs. 38.2% and 20.6% vs. 39.4%, respectively. Data additionally showed median fenebrutinib concentration within the cerebrospinal fluid of seven subset participants after 12 weeks of continuous administration was 47.4 ng/mL, higher than several standard assays.
“Early findings from FENopta indicate that fenebrutinib is brain penetrant and has the potential to modulate MS-related pathophysiological processes,” Bar-Or and colleagues wrote.