Orelabrutinib highly effective in relapsing-remitting MS, based on MRI results

Based on MRI imaging data, orelabrutinib was highly effective in patients with relapsing-remitting MS in a double-blind, phase 2 trial. The treatment effect occurred quickly and was sustained through 24 weeks. The once daily (QD) 80 mg dose had the most favourable efficacy and safety profile and will be further evaluated in phase 3 studies.

Bruton’s tyrosine kinase (BTK) inhibitors have recently generated much interest as promising MS treatments. Orelabrutinib is a highly selective BTK inhibitor that achieves a high concentration in the brain. A phase 2 study (NCT04711148) enrolled 158 patients with relapsing-remitting MS to evaluate the efficacy and safety of orelabrutinib [1]. Participants were randomised 1:1:1:1 to placebo, orelabrutinib 50 mg QD, 80 mg QD, or 50 mg twice daily (BID). The placebo group switched to orelabrutinib 50 mg QD at week 13. The primary endpoint was the cumulative number of new gadolinium‐enhancing (Gd+) T1 brain lesions at week 12, based on MRI scans at weeks 4, 8, and 12.

Prof. Yan Xu (Peking Union Medical College Hospital, China) presented the results of the 115 participants of whom MRI data of all 3 MRI assessments was available. After 12 weeks, the cumulative number of new Gd+ T1 lesions was significantly lower in all 3 actively treated groups than with placebo. The orelabrutinib 80 mg QD group saw the highest reduction. The respective numbers of new Gd+ T1 lesions were:

• placebo (n=27): 4.34;
• orelabrutinib 50 mg QD (n=30): 1.14 (-73.8%; P=0.0278);
• orelabrutinib 50 mg BID (n=29): 0.82 (-81.0%; P=0.0073); and
• orelabrutinib 80 mg QD (n=29): 0.42 (-90.4%; P=0.0018).

The cumulative number of new/enlarging T2 lesions was also significantly lower in all 3 orelabrutinib groups between weeks 12 and 24. The incidence of treatment-emergent adverse events (TEAEs) at week 12 was similar across the 3 orelabrutinib groups and slightly higher than in the placebo group. Most TEAEs were of grade 1–2. There were no serious TEAEs in the 80 mg QD group.

1. Xu Y, et al. Positive Phase 2 results of orelabrutinib in patients with relapsing-remitting multiple sclerosis. P094, ACTRIMS 2025, 27 February–01 March 2025, West Palm Beach, FL, USA.

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Posted on 28 March 2025