Abstract Details

Title Pharmacokinetics and Pharmacodynamics of Ravulizumab in Adults with Generalized Myasthenia Gravis: Results from the Phase 3 CHAMPION MG Study

Topic Autoimmune Neurology

Presentation(s) P3 - Poster Session 3 (5:30 PM-6:30 PM)

Poster/Presentation
Number 9-002

Background

Ravulizumab has a long half-life, permitting maintenance dosing every 8 weeks. In the 26-week, randomized, double-blind, placebo-controlled phase (RCP) of the CHAMPION MG study (NCT03920293) ravulizumab provided rapid and sustained efficacy and was well tolerated in patients with AChR Ab+ gMG.

Objective To investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of the long-acting terminal complement C5 inhibitor ravulizumab in adults with anti-acetylcholine receptor antibody-positive (AChR Ab+) generalized myasthenia gravis (gMG).

Design/Methods

We analyzed data from 86 patients who received ravulizumab in the RCP of the CHAMPION MG study. The ravulizumab dose regimen was weight-based, with an initial loading dose of 2400–3000 mg on Day 1, and maintenance doses of 3000–3600 mg on Day 15 (Week 2) and then every 8 weeks. PK parameters were estimated from population-PK analyses and the PD effects of ravulizumab on serum free C5 concentrations were measured.

Results Therapeutic serum concentrations of ravulizumab (>175 µg/mL) were achieved by the end of the first infusion and maintained throughout the entire 26-week treatment period. Ravulizumab’s mean elimination half-life was 56.4 days (SD: 7.9 days). Following the final maintenance dose, mean C_max was 1558 µg/mL, and mean C_trough was 663 µg/mL; no differences were noted between weight categories. Ravulizumab achieved immediate and complete (serum free C5 <0.5 μg/mL) inhibition of terminal complement, and this was sustained throughout treatment in all patients. No treatment-emergent anti-drug antibodies were observed.

Conclusions

Weight-based dosing of ravulizumab in patients with AChR Ab+ gMG achieved therapeutic serum concentrations immediately after the first dose, and these were maintained, irrespective of patient body weight, through 26 weeks of treatment with maintenance dosing every 8 weeks. Inhibition of serum free C5 was immediate, complete, and sustained throughout the treatment period.

Authors/Disclosures
Tuan H. Vu, MD (University of South Florida) PRESENTER	Dr. Vu has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Dianthus. Dr. Vu has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ImmunAbs. 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 $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Dr. Vu has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen (Horizon). 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 Johnson & Johnson. 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 Argenx. 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 Mass Gen Hospital/Healy Platform Study. The institution of Dr. Vu has received research support from ARGENX. The institution of Dr. Vu has received research support from Horizon/Amgen. 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/Johnson & Johnson. The institution of Dr. Vu has received research support from Immunovant. The institution of Dr. Vu has received research support from Regeneron. The institution of Dr. Vu has received research support from Dianthus. The institution of Dr. Vu has received research support from COUR.
Stephan Ortiz, PhD (Alexion, AstraZeneca Rare Disease)	Dr. Ortiz has received personal compensation for serving as an employee of Alexion/AstraZeneca Rare Disease. Dr. Ortiz has stock in Alexion.
	No disclosure on file
	No disclosure on file
Renato Mantegazza, MD	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.
Kathleen Beasley, PharmD (Alexion Pharmaceuticals)	Dr. Beasley has received personal compensation for serving as an employee of Alexion, AstraZeneca Rare Disease. Dr. Beasley has received stock or an ownership interest from Alexion, AstraZeneca Rare Disease.
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.