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Randomized Controlled Trial
. 2024 Dec;31(12):e16490.
doi: 10.1111/ene.16490. Epub 2024 Oct 7.

Time to response with ravulizumab, a long-acting terminal complement inhibitor, in adults with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis

Ali A Habib  1 , Michael Benatar  2 , Tuan Vu  3 , Andreas Meisel  4 , Shahram Attarian  5 , Masahisa Katsuno  6 , Serena Liao  7 , Kathleen N Beasley  7 , James F Howard Jr  8
Affiliations
Randomized Controlled Trial

Time to response with ravulizumab, a long-acting terminal complement inhibitor, in adults with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis

Ali A Habib et al. Eur J Neurol. 2024 Dec.

Abstract

Background and purpose: The efficacy and safety of ravulizumab, a terminal complement C5 inhibitor, in adults with anti-acetylcholine receptor antibody-positive (AChR Ab+) generalized myasthenia gravis (gMG) were demonstrated in the CHAMPION MG study (NCT03920293). This analysis aimed to characterize the latency to onset of a clinically meaningful therapeutic effect for ravulizumab.

Methods: Post hoc analysis of data collected for up to 60 weeks from CHAMPION MG was performed to assess the timing of response to ravulizumab. Response was analyzed based on reductions of ≥2 and ≥3 points (minimal clinically important differences [MCIDs]) in Myasthenia Gravis-Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) total scores, respectively, and on more rigorous reductions of ≥3 and ≥5 points, respectively. Time to first response was assessed using the Kaplan-Meier product-limit method.

Results: The median (95% confidence interval) time to first response was 2.1 (2.1-2.6) and 4.1 (2.3-10.0) weeks for reductions of ≥2 and ≥3 points in MG-ADL total score, respectively (n = 139), and 4.1 (2.1-10.0) and 18.3 (11.0-33.4) weeks for reductions of ≥3 and ≥5 points in QMG total score, respectively (n = 134). Cumulative response rates at Week 60 (data cut-off) were 88% and 82% for ≥2- and ≥3-point MG-ADL score reductions, respectively, and 86% and 59% for ≥3- and ≥5-point QMG score reductions, respectively.

Conclusions: The median times to MCID with ravulizumab treatment in patients with AChR Ab+ gMG were ~2 weeks and ~4 weeks based on MCID MG-ADL and QMG total score reductions, respectively.

Keywords: activities of daily living; complement inactivating agents; muscle strength; myasthenia gravis, generalized.

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Conflict of interest statement

Ali A. Habib has served as a medical advisor and speaker on behalf of Alexion, AstraZeneca Rare Disease, has received research support from Alexion, AstraZeneca Rare Disease, and has received research support and honoraria from argenx, UCB, Immunovant, Cabaletta Bio, Pfizer, Genentech/Roche, Viela Bio/Horizon, and Regeneron. Michael Benatar reports consulting for Alector, Alexion, Annexon, Arrowhead, Biogen, Cartesian, Denali, Eli Lilly, Horizon, Immunovant, Janssen, Novartis, Roche, Sanofi, Takeda, UCB, and uniQure. Tuan Vu is the USF Site Principal Investigator for MG clinical trials sponsored by Alexion, AstraZeneca Rare Disease, argenx, UCB Pharma, Amgen, Johnson & Johnson, Immunovant, Dianthus, Sanofi, Regeneron, and Cartesian Therapeutics, and receives speaker and/or consultant honoraria from Alexion, AstraZeneca Rare Disease, UCB, Dianthus, ImmunAbs, and argenx. Andreas Meisel has received speaker honoraria, consulting fees, or financial research support (paid to institution) from Alexion, AstraZeneca Rare Disease, argenx, Axunio, Grifols, Hormosan, Janssen, Merck, Octapharma, and UCB. He serves as chairman of the medical advisory board of the German Myasthenia Gravis Society. Shahram Attarian has received honoraria from Biogen, Roche, Sanofi, Pfizer, Alnylam, argenx, LFB, and Pharnext, and has received research support (paid to institution) from Pfizer, Biogen, and LFB. Masahisa Katsuno has received speaker honoraria from Biogen Japan, Chugai, and Eisai, and financial research support from Alexion, AstraZeneca Rare Disease, argenx, Eisai, and Mitsubishi‐Tanabe. Serena Liao is an employee of Alexion, AstraZeneca Rare Disease and owns stock in AstraZeneca. Kathleen N. Beasley was an employee of Alexion, AstraZeneca Rare Disease and owned stock in AstraZeneca at the time the study was conducted. James F. Howard Jr has received research support (paid to institution) from Ad Scientiam, argenx, Cartesian Therapeutics, the Centers for Disease Control and Prevention (Atlanta, GA, USA), the Myasthenia Gravis Foundation of America, the Muscular Dystrophy Association, the National Institutes of Health (including the National Institute of Neurological Disorders and Stroke and the National Institute of Arthritis and Musculoskeletal and Skin Diseases), PCORI, and UCB Bioscience, honoraria from Ad Scientiam, AcademicCME, Alexion, AstraZeneca Rare Disease, argenx, Biohaven Ltd., Biologix Pharma, CheckRare CME, F. Hoffman‐LaRoche Ltd., Horizon Therapeutics plc (now Amgen), Medscape CME, Merck EMB Serono, Novartis Pharmaceuticals, PeerView CME, Physicians' Education Resource (PER) CME, PlatformQ CME, Regeneron Pharmaceuticals, Sanofi US, UCB Biosciences, and Zai Laboratories, and non‐financial support from Alexion, AstraZeneca Rare Disease, argenx, Cartesian Therapeutics, Toleranzia AB, UCB Biosciences, and Zai Laboratories.

Figures

FIGURE 1
FIGURE 1
Patient populations for the CHAMPION randomized controlled period (RCP), open‐label extension (OLE), and response analysis. MG‐ADL, Myasthenia Gravis–Activities of Daily Living.
FIGURE 2
FIGURE 2
Cumulative probability of response to ravulizumab based on (a) reduction in Myasthenia Gravis–Activities of Daily Living (MG‐ADL) total score and (b) reduction in Quantitative Myasthenia Gravis (QMG) total score. Results from 139 patients with MG‐ADL data and 134 patients with QMG data available at cut‐off.
FIGURE 3
FIGURE 3
Response rates for ravulizumab over time according to (a) a ≥2‐point reduction and (b) a ≥3‐point reduction in Myasthenia Gravis–Activities of Daily Living total score. Cumulative data may not sum due to rounding. L, loading dose; M, maintenance dose.
FIGURE 4
FIGURE 4
Response rates for ravulizumab over time according to (a) a ≥3‐point reduction and (b) a ≥5‐point reduction in Quantitative Myasthenia Gravis total score. Cumulative data may not sum due to rounding. L, loading dose; M, maintenance dose.
See this image and copyright information in PMC

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