Long-Term Safety, Tolerability, And Efficacy of Efgartigimod in Patients with Generalized Myasthenia Gravis: Concluding Analyses from the ADAPT+ Study (S5.006)

Objective:

To evaluate long-term safety and efficacy of efgartigimod.

Background:

Efgartigimod is a human IgG1 antibody Fc-fragment that reduces total IgG and pathogenic IgG autoantibody levels through neonatal Fc receptor blockade. ADAPT was a 26-week, global, multicenter, randomized, controlled, phase 3 trial evaluating efgartigimod in patients with generalized myasthenia gravis (gMG). Patients who completed ADAPT were eligible to enroll in the ADAPT+ open-label extension study.

Design/Methods:

Efgartigimod (10 mg/kg IV) was administered in cycles of once-weekly infusions for 4 weeks, with subsequent cycles initiated based on clinical evaluation. The primary objective in ADAPT+ was to evaluate long-term safety and tolerability of efgartigimod in patients with gMG. Long-term efficacy was also assessed utilizing Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scales.

Results:

90% of patients (151/167) from ADAPT entered ADAPT+ and 145 (111 anti-AChR-Ab+/34 anti-AChR-Ab-) have received ≥1 cycle as of January 2022. With 217.5 patient-years of follow-up (mean duration per patient: 548 days), the most common adverse events were headache (25%), concomitant COVID-19 infection (15%), nasopharyngitis (14%), diarrhea (10%), and urinary tract infections (9%) which were mostly mild-moderate and did not increase in frequency with subsequent cycles. AChR-Ab+ patients with ≥1 year of follow-up across ADAPT/ADAPT+ (n=95) received a median (range) 5.0 (0.4–7.6) cycles per year. In all anti-AChR-Ab+ patients (n=111), consistent improvements in MG-ADL (mean[SE] change week 3 of cycle 1: −5.0[0.33]; up to 14 cycles) and QMG (−4.7[0.41]; up to 7 cycles) scores were observed during each cycle, mirroring repeatable reductions in total IgG (mean[SE] reduction: −55.9% [1.15]; up to 7 cycles) and anti-AChR autoantibody levels (−56.1%[1.43]; up to 7 cycles).

Conclusions:

These analyses of ADAPT+ suggest long-term efgartigimod treatment is well-tolerated and results in consistent and repeatable reductions in IgG antibody levels and clinical outcomes (MG-ADL and QMG) in patients with gMG. Disclosure: Dr. Pasnoor has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Argenx BVBA. Dr. Pasnoor has received personal compensation in the range of $500-$4,999 for serving as a Consultant for catalyst. Dr. Pasnoor has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda Pharmaceuticals. Dr. Pasnoor has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen Pharmaceutical. Dr. Pasnoor has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunovant. Dr. Pasnoor has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Pasnoor has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for catalyst pharmaceuticals. Dr. Pasnoor has received research support from NIH. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CSL. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alnylam. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Grifols. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Octapharma. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pfizer. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Powell Mansfield. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Akcea. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ionis. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunovant. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Momenta (now J&J). Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NovoNordisk. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Takeda. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunovant. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Bril has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Akcea. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alnylam. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CSL. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. The institution of Dr. Bril has received research support from UCB. The institution of Dr. Bril has received research support from Argenx. The institution of Dr. Bril has received research support from Momenta (now J&J). The institution of Dr. Bril has received research support from Immunovant. The institution of Dr. Bril has received research support from Alexion. The institution of Dr. Bril has received research support from Takeda. The institution of Dr. Bril has received research support from Grifols. The institution of Dr. Bril has received research support from CSL. The institution of Dr. Bril has received research support from Octapharma. The institution of Dr. Bril has received research support from Akcea. The institution of Dr. Bril has received research support from Ionis. The institution of Dr. Bril has received research support from Viela Bio (now Horizon). Dr. Bril has received intellectual property interests from a discovery or technology relating to health care. Dr. Karam has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alnylam. Dr. Karam has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ionis. Dr. Karam has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Karam has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Argenx. Dr. Karam has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Karam has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neuroderm. Dr. Peric has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Argenx. Dr. Peric has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mylan. Dr. De Bleecker has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ArgNX. Dr. De Bleecker has received personal compensation in the range of $0-$499 for serving as a Consultant for Biogen. Dr. De Bleecker has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. De Bleecker has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. De Bleecker has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for CSL Behring. Dr. Murai has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion Pharmaceuticals. Dr. Murai has received personal compensation in the range of $500-$4,999 for serving as a Consultant for argenx. Dr. Murai has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Murai has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Chugai Pharmaceutical. The institution of Dr. Murai has received research support from Japan Blood Products Organization. Prof. Meisel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Prof. Meisel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for argnx. Prof. Meisel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Prof. Meisel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Prof. Meisel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for argnx. Prof. Meisel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Prof. Meisel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for argnx. Prof. Meisel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Grifols. Prof. Meisel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Hormosan. The institution of Prof. Meisel has received research support from Octapharma. The institution of Prof. Meisel has received research support from Alexion. Prof. Meisel has received personal compensation in the range of $500-$4,999 for serving as a Auditor with Deutsche Myasthenie Gesellschaft / Bundesinstitut für Qualität und Patientensicherheit. Dr. Beydoun has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alnylam. 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 $10,000-$49,999 for serving as a Consultant for Akcea. Dr. Beydoun has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Tanabe. Dr. Beydoun has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Beydoun has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CSL. Dr. Beydoun has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Catalyst. 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 $5,000-$9,999 for serving on a Speakers Bureau for Akcea. Dr. Beydoun has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for CSL. Dr. Beydoun has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Grifols. Dr. Beydoun has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Takeda. The institution of Dr. Beydoun has received research support from UCB. The institution of Dr. Beydoun has received research support from Ra Pharma. The institution of Dr. Beydoun has received research support from Alexion. The institution of Dr. Beydoun has received research support from Argenx. The institution of Dr. Beydoun has received research support from Catalyst. The institution of Dr. Beydoun has received research support from AB Sciences. The institution of Dr. Beydoun has received research support from Pfizer. Dr. Vu has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BPL. Dr. Vu has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda. Dr. Vu has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ARGENX. Dr. Vu 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. Dr. Vu has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Dr. Vu has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion. Dr. Vu has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for CSL Behring. Dr. Vu has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for AbbVie. Dr. Vu has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Argenx. Dr. Vu has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for MedScape. The institution of Dr. Vu has received research support from CSL Behring. The institution of Dr. Vu has received research support from Alexion. The institution of Dr. Vu has received research support from RA Pharma/UCB. The institution of Dr. Vu has received research support from Mitsubishi Tanaka. The institution of Dr. Vu has received research support from Mass Gen Hospital/Healy Platform Study. The institution of Dr. Vu has received research support from Amylyx Pharma. The institution of Dr. Vu has received research support from ARGENX. The institution of Dr. Vu has received research support from Alector. The institution of Dr. Vu has received research support from Annexon. The institution of Dr. Vu has received research support from Apellis. The institution of Dr. Vu has received research support from Cytokinetics. The institution of Dr. Vu has received research support from Sanofi. The institution of Dr. Vu has received research support from Horizon. The institution of Dr. Vu has received research support from Woolsey Pharma. The institution of Dr. Vu has received research support from CSL Behring. The institution of Dr. Vu has received research support from Cartesian Therapeutics. The institution of Dr. Vu has received research support from Janssen/Momenta. Peter Ulrichts has received personal compensation for serving as an employee of argenx. Peter Ulrichts has stock in argenx. Dr. Van Hoorick has received personal compensation for serving as an employee of argenx. Mrs. T’joen has received personal compensation for serving as an employee of argenx. Dr. Utsugisawa has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for argenx. Dr. Utsugisawa has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB pharma. Dr. Utsugisawa has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen pharma. Dr. Utsugisawa has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Viela Bio. Dr. Utsugisawa has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Chugai. Dr. Utsugisawa has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Mitsubisi Tanabe pharma. Dr. Utsugisawa has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Utsugisawa has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for argenx. Dr. Utsugisawa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion phama. Dr. Utsugisawa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Japan Blood Products Organization. Dr. Utsugisawa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB. The institution of Dr. Verschuuren has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. The institution of Dr. Verschuuren has received personal compensation in the range of $0-$499 for serving as a Consultant for Rapharma. Dr. Verschuuren has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. The institution of Dr. Verschuuren has received research support from Argenx. Dr. Mantegazza has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Mantegazza has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Dr. Mantegazza has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for argenx. Dr. Mantegazza has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Mantegazza has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for SERB. The institution of Dr. Mantegazza has received research support from Alpine Immune Sciences, Inc. 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 BVBA. 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 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 $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunivant. 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 Viela Bio (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 $10,000-$49,999 for serving on a Speakers Bureau for Academic 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. The institution of Dr. Howard has received research support from Alexion Pharmaceuticals. The institution of Dr. Howard has received research support from argenx BVBA. The institution of Dr. Howard has received research support from Ra Pharma (now 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 Millenium Pharmaceuticals. 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. in collaboration with the ADAPT Investigator Study Group has nothing to disclose.