Obexelimab for Relapsing MS Meets Primary Endpoint in Phase 2 Trial
In the Phase 2 MoonStone trial of obexelimab in relapsing multiple sclerosis (RMS), the investigational drug met the primary endpoint with a 95% relative reduction in new gadolinium (Gd)-enhacing (GdE) T1 hyperintense lesions over week 8 and week 12 compared with placebo (p=0.0009). The results were announced by Zenas BioPharma, Inc.
Obexelimab is a bifunctional monoclonal antibody designed to address the pathogenic role of the B cell lineage in chronic autoimmune diseases by binding to CD19 and FcyRllb to constrain cell activity without depleting them.
“These profound MoonStone trial results, including the near elimination of new GdE T1 lesions, provide strong evidence of the deep and sustained inhibitory mechanism of obexelimab and further validate the potential for obexelimab to become a meaningful therapy across multiple autoimmune diseases,” said Lonnie Moulder, Founder and Chief Executive Officer of Zenas.
The randomized, double-blind, placebo-controlled trial enrolled 116 patients who were randomized 2:1 to receive either 250 mg of obexelimab or placebo through subcutaneous injection once a week over a 12-week treatment period. Following the 12-week double-blinded phase, all patients entered a 12-week open-label period, with those previously receiving placebo transitioned over to treatment with obexelimab.
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Outcomes were evaluated using magnetic resonance imaging (MRI) endpoints commonly used in other clinical trials on the RMS population with annualized relapse rate as an endpoint. In addition to the primary endpoint, MoonStone had secondary and exploratory endpoints including standardized assessments, imagining, and biomarkers to measure the effect of obexelimab on disease progression.
By week 8 and through week 12, obexelimab almost completely inhibited new GdE T1 hyperintense lesions, which are markers of active inflammation. The adjusted mean number of new GdE T1 hyperintense lesions per scan in the obexelimab group was 0.01 (95% CI: 0.00, 0.06) compared to 0.23 (95% CI: 0.11, 0.51) with placebo. Obexelimab also significantly reduced the cumulative number of new and/or enlarging T2 weighted hyperintense lesions compared to placebo. The safety profile of the drug remained consistent with that of previous trials. The most common adverse effect was mild reactions at the injection site.
“The observed clinical activity in the MoonStone trial, combined with obexelimab’s unique inhibitory mechanism of action, subcutaneous self-administration and tolerability profile, position obexelimab as a potential option to broadly address the pathogenic role of B cells in autoimmune diseases,” said Lisa von Moltke, M.D., Head of Research and Development and Chief Medical Officer of Zenas. “With these highly statistically significant data, we look forward to reporting 24-week data in the first quarter of 2026, which will include additional secondary and exploratory endpoints that may inform obexelimab’s potential impact on disability progression and help us determine next steps for future development of obexelimab in relapsing MS.”
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