Claseprubart Heads to Phase 3 Study of Myasthenia Gravis Following Positive MaGic Trial

Tuan Vu, MD

Newly announced data from the phase 2 MaGic trial (NCT06282159) showed that treatment with claseprubart (Dianthus Therapeutics), an investigational complement-targeting agent, led to statistically significant improvements in a number of efficacy-related outcomes in patients with generalized myasthenia gravis (gMG). Based on these findings, Dianthus is planning an end-of-phase 2 meeting with the FDA to align on a phase 3 study of claseprubart, pushing the treatment one step closer to potential approval.¹

MaGic, a double-blind, placebo-controlled trial, included 65 patients with acetylcholine receptor antibody positive (AChR+) gMG who received subcutaneous claseprubart or placebo every 2 weeks (Q2W) at a dose of 300 mg/2mL or 600 mg/4mL. After 13 weeks of treatment, both groups showed statistically significant and clinically meaningful improvements in the primary and secondary end points of Myasthenia Gravis Activities of Daily Living (MG-ADL) score and Quantitative Myasthenia Gravis (QMG) score.

Overall, those in the claseprubart 300 mg group had clinically meaningful mean improvements of 4.6 points in MG-ADL scores (placebo-adjusted improvement, 1.8 points; P = .0013), with statistically significant changes observed as early as week 1. A greater, but nonsignificant effect was seen in the 600 mg group, with mean MG-ADL improvements of 5.4 points (placebo-adjusted, 2.6 points; P = .0006) that were seen as early as week 1. Of note, the difference in MG-ADL scores between the claseprubart 300 mg and 600 mg groups never reached statistically significant at any time point.

"gMG is a chronic condition that can be treated with complement and FcRn inhibitors. The ideal drug should provide continuous symptom control and have low infection risks, infrequent side effects, convenient dosing schedule, and minimal administration burden," Tuan Vu, MD, professor of neurology at the University of South Florida Morsani College of Medicine, said in a statement. "If these impressive results were replicated in a Phase 3 trial, claseprubart may be a differentiated treatment option for patients with gMG."

At the 13-week mark, those in the claseprubart 300 mg and 600 mg Q2W groups achieved statistically significant mean improvements of 4.4 and 4.5 points, respectively, in QMG score, with effects seen as early as week 1 in both groups. Overall, this led to respective placebo-adjusted improvements of 2.4 (P = .0144) and 2.5 (P = .0111), with no significant difference observed between the investigational cohorts.

In the study, those in the claseprubart 300 mg Q2W dose group showed statistically significant and clinically meaningful improvements in other end points, including Minimal Symptom Expression (MSE), Myasthenia Gravis Composite (MGC) score, and Myasthenia Gravis Quality of Life Scale (MG-QoL-15r). More specifically, it led to a 23% placebo-adjusted change in MSE (P = .0550), –5.6-point difference in mean MGC scores (P = .0008), and a –2.2-point placebo-adjusted difference in MG-QoL-15r (P = .0414).

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Claseprubart, a monoclonal antibody engineered to selectively target the classical pathway by inhibiting only the active form of the C1s protein, was shown to be safe and well tolerated in both dosed groups. Over the study period, there were no symptoms indicative of autoimmune activation, no infection signals, and no related serious bacterial infections. In addition, there were no serious adverse events in the active group, with injection site reactions that were considered infrequent and generally mild.

Otherwise known as DNTH103, claseprubart is also currently being studied in a phase 3 trial of chronic inflammatory demyelinating polyneuropathy (CIDP) and a phase 2 study of multifocal motor neuropathy (MMN). The CIDP trial, dubbed CAPTIVATE (NCT06858579), is a large-scale study of nearly 480 patients, with expected results to come in the 2^nd half of 2026. Dianthus’ MoMeNtum trial, which assesses the efficacy and safety of claseprubart in 36 patients with MMN, is anticipated to have topline data read out in the 2^nd half of 2026.

"Based on the comparable efficacy data demonstrated in MaGic by the 300mg and 600mg Q2W doses, as well as encouraging early data from the open-label extension, we are planning for an end-of-Phase 2 meeting with the FDA to align on the proposed design of a Phase 3 trial for claseprubart in Myasthenia Gravis that investigates both 300mg Q2W and 300mg Q4W doses vs. placebo," Marino Garcia, president and chief executive officer at Dianthus, said in a statement.

Claseprubart, a complement-inhibiting treatment, binds only to the activated C1s enzyme, blocking downstream C4/C2 cleavage, thus preventing C3b opsonization and C5/MAC formation triggered by AChR antibodies in gMG. The agent is also anti-C1s but is designed to bind the active form with extended half-life and low-volume subcutaneous self-administration tailored for neuromuscular conditions like gMG.

Garcia added, "2026 will be a catalyst-rich year, with the initiation of the Phase 3 gMG trial followed by results from the interim responder analysis of the Phase 3 CAPTIVATE trial in Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) and top-line results from the Phase 2 MoMeNtum trial in Multifocal Motor Neuropathy (MMN), both in 2H’26."

REFERENCE
1. Dianthus Therapeutics Announces Positive Data for Claseprubart (DNTH103) from the Phase 2 MaGic Trial in Generalized Myasthenia Gravis, Supporting Its Potential Best-In-Class Profile. News release. Dianthus Therapeutics. September 8, 2025. Accessed September 8, 2025.