New therapies and applications

In a small retrospective analysis, glucagon-like peptide-1 receptor agonists (GLP-1RAs) appeared to be safe for weight management in patients with MS, but no evidence was found for improvement in MS-related disability or biomarkers of disease activity and progression.

GLP-1RAs are approved for the treatment of type 2 diabetes and obesity and have increasingly been prescribed to patients with MS in recent years. However, their safety and efficacy in the MS population have not been well established. Beyond metabolic indications, interest within the MS community has been driven by the potential neuroprotective effects in preclinical models and other neurological conditions. These proposed effects are thought to be mediated by the modulation of metabolic and inflammatory pathways. Nonetheless, both the safety profile and the impact of GLP-1RAs on clinical outcomes in MS remain incompletely defined.

Dr Rachel Rodin (Harvard Medical School, MA, USA) and colleagues conducted a retrospective single-centre study to assess the safety and clinical effect of GLP-1RAs on body mass index (BMI), Expanded Disability Status Scale (EDSS), and Timed 25-Foot Walk (T25-FW) performance in MS patients [1].

The study cohort comprised 131 patients from the Brigham and Women’s Hospital MS Center (Boston, USA) who were prescribed a GLP-1RA between 2010 and 2025. The majority were women (n=108, 82%). The mean age was 53 years (range 28–80); 98 patients (75%) had relapsing-remitting MS (RRMS) and 33 (25%) had secondary progressive MS (SPMS). Mean baseline BMI was 36.9 (range 21.5–6), and mean EDSS was 3.1 (range 0.0–8.5). Semaglutide was the most frequently prescribed GLP-1RA (31%), followed by tirzepatide (11%) and dulaglutide (9%). Nearly half of the patients (45%) switched between GLP-1RAs during the study period for various reasons.

Over a mean treatment duration of 29 months, BMI decreased by an average of 4 points. Mean weight loss was 11.3 kg (P<0.001). GLP-1RA treatment was generally safe and well tolerated; 53 patients (42%) reported adverse events, including moderate-to-severe events in 12 (9%).

Despite the significant metabolic effects, no statistically significant changes were observed in EDSS or T25-FW after maximal treatment duration. EDSS scores decreased by 0.5–2.0 points in 22 patients (17%) and increased by 0.5–4.0 points in 23 patients (18%), but the differences were not statistically significant. Clinical relapses occurred in 10 patients (7%), and 6 patients (5%) developed new or enlarging T2 lesions on MRI. Only 2 of these events occurred in patients receiving high-efficacy MS therapies.

One potential explanation for the absence of measurable neurological benefit is the limited penetration of GLP-1RAs across the blood-brain barrier. Overall, while GLP-1RAs appear safe and effective for weight reduction in patients with MS, this study did not demonstrate a meaningful impact on disease activity or disability progression.

Rodin RE, et al. Retrospective analysis of GLP-1 receptor agonists in multiple sclerosis. P422, ACTRIMS Congress 2026, 4–7 February, San Diego, California, USA.

Week 12 results from the phase 2 MoonStone trial provide the first clinical evidence supporting the efficacy of obexelimab, a novel humanised bifunctional monoclonal antibody, in patients with relapsing-remitting MS (RRMS). No new safety concerns arose from the study results.

Obexelimab is designed to inhibit B-cell activation and function by co-engaging cluster of differentiation 19 (CD19) and the inhibitory Fcγ receptor IIb (FcγRIIb). As explained by Prof. Amit Bar-Or (University of Pennsylvania, PA, USA), obexelimab “mimics the inhibitory signalling normally mediated by immune complexes.” He further noted: “It has been shown to potently inhibit B-cell antibody production, proliferation, cytokine secretion, and antigen presentation to T-cells” [1].

MoonStone (NCT06564311) is the first phase 2 trial evaluating this novel therapeutic mechanism in MS. This randomised, double-blind, placebo-controlled study enrolled 116 adults with RRMS and an Expanded Disability Status Scale (EDSS) score ≥5.5. Participants were randomised 2:1 to receive weekly subcutaneous obexelimab 250 mg (n=72) or placebo (n=38) for 12 weeks, after which the placebo group transitioned to active treatment. The primary endpoint was the cumulative number of new gadolinium-enhancing T1-weighted (Gd+) hyperintense lesions at weeks 8 and 12.

“Obexelimab met the primary endpoint, with a 95% relative reduction in the cumulative number of Gd+ T1 lesions after 8 and 12 weeks compared with placebo,” said Prof. Bar-Or. The mean number of new lesions per scan was 0.01 in the obexelimab group versus 0.23 in the placebo group (P=0.0009). The cumulative number of new lesions during this period was 2 among 72 patients receiving obexelimab, compared with 19 among 38 patients receiving placebo. Obexelimab was also associated with an 81% relative reduction in new and/or enlarging T2 lesions (P=0.0018), indicating near-complete suppression of inflammatory lesion activity over 12 weeks.

Prof. Bar-Or further noted that mean B-cell values decreased to approximately 37% at weeks 8 and 12 in the experimental group. Consistent with obexelimab’s inhibitory (rather than depleting) mechanism, these values remained within the normal range.

The safety profile was consistent with previous trials in other indications. The most common adverse events were mild injection site reactions (11.5%). Overall, these findings support continued clinical development of obexelimab in RRMS.

Okuda DT, et al. Week 12 results from MoonStone, a phase 2 study of obexelimab in relapsing multiple sclerosis. LB1.3, ACTRIMS Congress 2026, 4–7 February, San Diego, California, USA.

GLP-1RAs are safe for MS patients but do not alter disease course

Novel monoclonal antibody obexelimab demonstrates efficacy in phase 2 trial