Abstract Details

Title A Phase 3, Open-Label, Multicenter Study To Evaluate Eculizumab In Adolescents With Refractory Generalized Myasthenia Gravis

Topic Autoimmune Neurology

Presentation(s) S5 - Autoimmune Neurology: NMOSD and MG, a Focus on Treatment Trials (2:36 PM-2:48 PM)

Poster/Presentation
Number 009

Background Patients with AChR Ab+ gMG have uncontrolled complement activation leading to neuromuscular junction destruction and impaired neuromuscular transmission, resulting in debilitating fatigable muscle weakness. In addition to established treatment, there remains a need for targeted therapies for MG. Eculizumab, a terminal complement C5 inhibitor, has demonstrated safety and efficacy in adults with refractory AChR Ab+ gMG.

Objective To evaluate eculizumab for the treatment of adolescents with refractory anti-acetylcholine receptor antibody-positive (AChR Ab+) generalized myasthenia gravis (gMG).

Design/Methods A phase 3, open-label, multicenter study was conducted in adolescents 12–17 years (NCT03759366). Eculizumab was administered using a weight-based dosing regimen, with weekly induction (1–2 doses of 600 mg or 4 doses of 900 mg) followed by 2-weekly maintenance (300–1200 mg). The primary endpoint was change from baseline to week 26 in Quantitative Myasthenia Gravis (QMG) total score. Multiple secondary endpoints were assessed, including change from baseline to week 26 in MG-Activities of Daily Living (MG-ADL) total score. Pharmacodynamics and safety were also assessed.

Results Eleven adolescents (mean age 14.8±1.8 years) were enrolled, of whom six were receiving chronic intravenous immunoglobulin (IVIg). Ten patients completed the primary evaluation period. Least-square mean changes from baseline at week 26 were -5.8 (standard error [SE] 1.2; p=0.0004) for QMG total score and -2.3 (SE 0.6; p=0.0017) for MG-ADL total score. Similar changes were observed irrespective of chronic IVIg treatment. Overall, the primary and all secondary efficacy endpoint analyses met statistical significance at week 1. Improvements were sustained through week 26. Complete terminal complement inhibition was sustained throughout 26 weeks in all patients. Treatment-emergent adverse events were all mild/moderate and predominantly unrelated to eculizumab. Three patients experienced six serious adverse events (MG worsening [3], MG crisis, peritonsillar abscess, pyrexia). No meningococcal infections were reported.

Conclusions Eculizumab was efficacious and well-tolerated in adolescents with refractory AChR Ab+ gMG.

Authors/Disclosures
John Brandsema, MD (Children's Hospital of Philadelphia, Division of Neurology) PRESENTER	Dr. Brandsema has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Brandsema has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Brandsema has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for PTC Therapeutics. Dr. Brandsema has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sarepta. Dr. Brandsema has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Brandsema has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Argenx. Dr. Brandsema has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Janssen. Dr. Brandsema has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dyne. Dr. Brandsema has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Fibrogen. Dr. Brandsema has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda. Dr. Brandsema has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Edgewise. The institution of Dr. Brandsema has received research support from Novartis. The institution of Dr. Brandsema has received research support from Biogen. The institution of Dr. Brandsema has received research support from Alexion. The institution of Dr. Brandsema has received research support from CSL Behring. The institution of Dr. Brandsema has received research support from Pfizer. The institution of Dr. Brandsema has received research support from PTC Therapeutics. The institution of Dr. Brandsema has received research support from Sarepta. The institution of an immediate family member of Dr. Brandsema has received research support from Argenx. The institution of Dr. Brandsema has received research support from Astellas. The institution of Dr. Brandsema has received research support from Fibrogen. The institution of Dr. Brandsema has received research support from Genentech. The institution of Dr. Brandsema has received research support from Janssen. The institution of Dr. Brandsema has received research support from Scholar Rock.
Matthew Ginsberg, MD (Akron Children's Hospital)	Dr. Ginsberg has nothing to disclose.
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Niraja S. Suresh, MD (Lakeland Regional Medical Center)	Dr. Suresh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Anylam . Dr. Suresh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexeion. Dr. Suresh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenex. Dr. Suresh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Takeda . Dr. Suresh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Pfizer.
Emmanuelle R. Tiongson, MD (Childrens Hospital Los Angeles)	Dr. Tiongson has nothing to disclose.
Hideo Yamanouchi, MD (Pediatrics, Saitama Medical University)	Dr. Yamanouchi has nothing to disclose.
Glen Frick, MD, PhD	Dr. Frick has received personal compensation for serving as an employee of AstraZeneca/Alexion Rare Disease. Dr. Frick has stock in AstraZeneca/Alexion Rare Disease.
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	No disclosure on file
James F. Howard, Jr., MD, FAAN (The University of North Carolina, Dept of Neurology, CB 7025)	Dr. Howard has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for arenx . Dr. Howard has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Regeneron Pharmaceuticals. Dr. Howard has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion Pharmaceuticals. Dr. Howard has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ra Pharma (now UCB Biosciences). Dr. Howard has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon Therapeutics. Dr. Howard has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi US. Dr. Howard has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Howard has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Academic CME. Dr. Howard has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for PeerView CME. Dr. Howard has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Platform Q CME. Dr. Howard has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Zai Laboratories. Dr. Howard has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Medscape CME. Dr. Howard has stock in General Electric dividends. Dr. Howard has stock in Johnson & Johnson dividends. Dr. Howard has stock in Pfizer dividends. An immediate family member of Dr. Howard has stock in GlaxoSmithKline dividends. An immediate family member of Dr. Howard has stock in GE Healthcare dividends. The institution of Dr. Howard has received research support from Alexion Pharmaceuticals. The institution of Dr. Howard has received research support from argenx . The institution of Dr. Howard has received research support from UCB Biosciences. The institution of Dr. Howard has received research support from NIH. The institution of Dr. Howard has received research support from Centers for Disease Control/Research Triangle Institute. The institution of Dr. Howard has received research support from Duke University (DCRI). The institution of Dr. Howard has received research support from Cartestian Therapeutics. Dr. Howard has a non-compensated relationship as a Scientific Advisiory Board member, Committee member with Myasthenia Gravis Foundation of America that is relevant to AAN interests or activities. Dr. Howard has a non-compensated relationship as a Committee member with American Assoc Neuromuscular and Electrodiagnostic Medicine that is relevant to AAN interests or activities.