CONFERENCE UPDATE: AAN 2021
Evobrutinib reduces neuroaxonal damage in multiple sclerosis
Evobrutinib is a highly selective Bruton’s tyrosine kinase (BTK) inhibitor that targets B-cells and myeloid cells including macrophages and microglia.1-3 In a previous phase 2 placebo-controlled, randomized trial among patients with relapsing multiple sclerosis, evobrutinib reduced total T1 gadolinium-enhancing (Gd+) lesions over 24 weeks when compared to placebo.4 The low annualized relapse rate (ARR) achieved by evobrutinib 75mg twice daily (BID) at week 48 (ARR=0.11; 95% CI: 0.04-0.25) was also maintained in the long-term extension study through 108 weeks (ARR=0.12; 95% CI: 0.06-0.22).5 Thereby, prior studies have demonstrated promising results with evobrutinib in treating relapsing multiple sclerosis.4,5
Blood neurofilament light chain (NfL) levels are a biomarker of neuroaxonal damage in multiple sclerosis, with proposed prognostic value for monitoring disease progression.6,7 To evaluate the effect of evobrutinib on blood NfL levels in patients with relapsing multiple sclerosis, a post-hoc analysis was conducted by Dr. Jens Kuhle from the Department of Biomedicine at University Hospital Basel, Switzerland, and colleagues. “These data on NfL dynamics are the first to be reported for any BTK inhibitor investigated for multiple sclerosis,” highlighted Dr. Kuhle.
The analysis consisted of three treatment arms (evobrutinib 25mg and 75mg once daily [QD] and 75mg BID) in addition to the placebo arm. NfL was measured blinded to the treatment allocation at baseline, week 4, 12 and 24. Drawing from the patient population randomized in the phase 2 study (modified intention-to-treat [mITT] population, n=267), 166 patients had NfL values at baseline and ≥1 post-baseline and were included in the NfL analysis population. At week 24, 148 patients remained in the NfL analysis population. No difference in baseline demographics between the mITT and NfL population was identified.
The effect of evobrutinib versus placebo on NfL over time was evaluated using a mixed model repeated measures (MMRM) model, controlling for significant baseline covariates including age (p=0.023), T2 lesion volume (p=0.008) and Expanded Disability Status Scale (EDSS) score (p=0.022).
At week 12 and 24, significant reduction of blood NfL levels was observed with the use of evobrutinib 75mg BID as compared to placebo with relative reductions of 18.9% and 16.8%, respectively (p=0.040). However, a significant reduction was observed with evobrutinib 75mg QD at week 12 but not at week 24. Also, there was no significant difference observed between evobrutinib 25mg QD and placebo.
In conclusion, evobrutinib 75mg BID significantly lowered blood NfL levels as early as week 12 with reduced levels maintained until week 24 in patients with relapsing multiple sclerosis. “These results are promising and indicate that an efficacious dose of evobrutinib 75mg BID has a beneficial effect on reducing neuro-axonal damage in multiple sclerosis,” concluded Dr. Kuhle.
Optimizing therapy in mantle cell lymphoma
Mantle cell lymphoma (MCL) is an uncommon but aggressive subtype of lymphoid malignancy, generally considered to have a poor prognosis.1 Although the disease responds well to initial treatment, relapse will inevitably occur,1