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Abstract Details

Minimal Symptom Expression with Claseprubart, an Active C1S Inhibitor, in Patients with Generalized Myasthenia Gravis
Autoimmune Neurology
P2 - Poster Session 02 (3:00 PM-4:00 PM)
1-008

Remission is a key goal in gMG and achieving minimal symptom expression (MSE) with claseprubart is a key treatment objective.

The classical complement pathway plays a significant role in generalized myasthenia gravis (gMG) pathology. Claseprubart is a potent monoclonal antibody that selectively targets the classical pathway by inhibiting active C1s (aC1s).

MaGic (NCT06282159), is a global Phase 2, randomized, double-blind, placebo-controlled trial. Patients treated with claseprubart (300mg, Q2W) were evaluated for MSE (MG-ADL ≤1 or QMG ≤3) compared with placebo. p-values were one-sided and nominal significance was assessed at an alpha= 0.1. Outcomes include proportion of patients achieving MSE at Week 13 and anytime during the study, earliest timepoint of MSE achievement, and durability defined as sustained MSE for at least 6 weeks.

At Week 13, 37% of claseprubart treated patients achieved MG-ADL-MSE versus 14% with placebo (OR 3.81; p=0.0550). 43% achieved MG-ADL-MSE at least once during the study versus 14% of placebo (OR: 4.72; p=0.0231). This effect was observed as early as Week 1 (median time to response was Week 3). Sustained remission-like states (for at least 6 weeks) were seen in all patients who achieved MSE. Similar results were observed using QMG minimum symptom expression threshold.

Claseprubart patients were more than four times more likely to achieve MSE than placebo patients and MSE was observed as early as week 1. Patients who achieved MSE maintained responses for at least 6 weeks. These results highlight the therapeutic potential of aC1s inhibition in AChR+ gMG.

Authors/Disclosures
Maria Ait Tihyaty (Johnson and Johnson Innovative Medicine)
PRESENTER
Dr. Ait Tihyaty has received personal compensation for serving as an employee of Dianthus Therapeutics.
Said R. Beydoun, MD, FAAN (University of Southern California Healthcare Consultation Center 2) Dr. Beydoun has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Dr. Beydoun has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. Dr. Beydoun has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Janssen. Dr. Beydoun has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for CSL. Dr. Beydoun has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for AstraZeneca. Dr. Beydoun has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Argenx. Dr. Beydoun has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. Dr. Beydoun has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pfizer. Dr. Beydoun has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Takeda. Dr. Beydoun has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Alnylam. Dr. Beydoun has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion. Dr. Beydoun has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for CSL. Dr. Beydoun has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for UCB. Dr. Beydoun has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Takeda. Dr. Beydoun has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for AstraZeneca. Dr. Beydoun has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Argenx. Dr. Beydoun has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Janssen. The institution of Dr. Beydoun has received research support from Abcuro. The institution of Dr. Beydoun has received research support from Sean Healy & AMG Center for ALS. The institution of Dr. Beydoun has received research support from Regeneron. The institution of Dr. Beydoun has received research support from RemeGen. The institution of Dr. Beydoun has received research support from Sanofi. The institution of Dr. Beydoun has received research support from Novartis.
Nils Erik Gilhus, MD Prof. Gilhus has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. Prof. Gilhus has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Prof. Gilhus has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Prof. Gilhus has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Prof. Gilhus has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Prof. Gilhus has received personal compensation in the range of $0-$499 for serving as a Consultant for Immunovant. Prof. Gilhus has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Johnson & Johnson. Prof. Gilhus has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Denka. Prof. Gilhus has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dianthus. Prof. Gilhus has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Grifols. Prof. Gilhus has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Prof. Gilhus has received personal compensation in the range of $0-$499 for serving as a Consultant for Takeda. Prof. Gilhus has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck. Prof. Gilhus has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NMD Pharma. Prof. Gilhus has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx, Alexion, UCB, Johnson & Johnson, Dianthus, Amgen. Prof. Gilhus has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck.
Amit Sachdev, MD (Michigan State University) Dr. Sachdev has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amgen. Dr. Sachdev has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. Dr. Sachdev has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion Pharmaceuticals. Dr. Sachdev has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB. Dr. Sachdev has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for argenx. The institution of Dr. Sachdev has received research support from UCB. The institution of Dr. Sachdev has received research support from argenx. The institution of Dr. Sachdev has received research support from Alexion Pharmaceuticals. The institution of Dr. Sachdev has received research support from Immunovant. The institution of Dr. Sachdev has received research support from Dianthus.
Caitlin Briggs Dr. Briggs has received personal compensation for serving as an employee of Dianthus Therapeutics. Dr. Briggs has stock in Dianthus Therapeutics.
Uzma H. Siddiqui, MD Dr. Siddiqui has or had stock in Dianthus Therapeutics.
Luke Hickey Mr. Hickey has received personal compensation for serving as an employee of Dianthus Therapeutics. Mr. Hickey has or had stock in Dianthus Therapeutics.
Marianna Lalla, MD, PhD Dr. Lalla has nothing to disclose.
Marek Smilowski, MD, PhD Dr. Smilowski has nothing to disclose.