Evobrutinib reduces relapse and MRI lesion activity

Evobrutinib significantly reduced MRI activity and patient numbers with qualified MS relapses regardless of baseline blood neurofilament light chain levels.

Patients with high NfL had a higher disease burden at baseline

NfL is an established biomarker of neuro-axonal damage in MS. In a post-hoc analysis of a phase 2 randomized trial (NCT02975349), evobrutinib 75 mg BID significantly lowered blood NfL levels at weeks 12 and 24. In a new analysis, the interaction of serum NfL (sNfL) levels and the effects of a BTK inhibitor in MS patients was evaluated for the first time. A total of 162 patients were included in the modified intent-to-treat population for whom NfL values at baseline were available (excluding the dimethyl fumarate control arm of the original study).

Participants were stratified by high dose (evobrutinib 75 mg QD or BID; n = 74) or placebo/low dose (placebo or evobrutinib 25 mg QD; n=88). They were also stratified by mean NfL levels on baseline as high (n=80) or low (n=82) NfL, with a cut-off value of 11.36 pg/ml. Treatment effect on qualified relapses was evaluated over 24 weeks, and on gadolinium-enhancing (Gd+) T1 and T2 lesions over weeks 12, 16, 20 and 24. Patients with high NfL had a higher disease burden at baseline, with more clinical relapses in the past 2 years, a higher EDSS score, more Gd+ T1 lesions, and a higher T2 lesion volume.

Treatments results showed the following:

The odds of qualified relapse were significantly higher in the high baseline sNfL group (OR 6.07; p=0038), and were significantly reduced in the evobrutinib high dose group versus placebo/low dose (OR 0.12; p=0.0028).
Patients with high sNfL at baseline had higher Gd+ T1 activity. The cumulative number of Gd+ T1 lesions was significantly reduced in the high evobrutinib dose group: both the high sNfL group (RR -69.2%; p=0.0018) and the low sNfL group (RR -69.4%; p=0.0102).
Patients with high sNfL at baseline also had higher T2 lesion activity. New or enlarging T2 activity was observed for the high EVO dose group, regardless of sNfL. In the high sNfL group, RR=54% (p=0.0458), in the low sNfL group, RR=73.4% (p=0.0012).

The authors concluded that these outcomes further support the value of blood NfL levels as a prognostic marker of MS disease activity.

Reference

Kuhle J, et al. Evobrutinib significantly reduces relapses and magnetic resonance imaging outcomes in patients with multiple sclerosis: association with baseline neurofilament light chain levels. Abstract 116, ECTRIMS 2021, 13–15 Oct.