Subanalysis of ADAPT Reveals Consistent Efficacy With Efgartigimod Among All Genders

Sarah Hoffmann, MD, PhD, MSc

Findings from analyses using data from the phase 3 ADAPT study (NCT03669588) showed no gender-specific treatment differences observed with efgartigimod (Vyvgart; Argenx) for generalized myasthenia gravis (gMG) across disease duration, BMI, and thymectomy. These results suggest efgartigimod shows consistent improvement across specific measures in gMG, regardless of the gender of the patients.¹

Among the 167 patients enrolled in ADAPT, 129 (77.2%) were antiacetylcholine receptor (AChR) antibody positive and 86 (66.7%) were women. The patients were randomly assigned 1:1 to either 10 mg/kg of efgartigimod or matched placebo for a 28-week treatment period, which consisted of up to 3- to 8-week treatment cycles. Between cycles of treatment, which were 4 infusions per cycle, each patient’s loss of treatment effect response was identified by predefined change in Myasthenia Gravis Activities of Daily Living (MG-ADL).

Presented at the 9th Congress of the European Academy of Neurology, held July 1 to 4, in Budapest, Hungary, by lead author Sarah Hoffmann, MD, PhD, MSc, a senior physician at the Integrated Myasthenia Gravis Center (IMZ) of the Charité in the Department of Neurology and Experimental Neurology at the NeuroCure Clinical Research Center (NCRC) of Charité University Medicine Berlin, in Germany. This analysis aimed to explore the potential gender-specific differences among specific gMG outcomes between efgartigimod and placebo in consideration of the Sex and Gender Equity in Research (SAGER) guidelines.

In the original trial, the primary end point was percentage of patients who were AChR-Ab+ and MG-ADL responders in the first treatment cycle and secondary end points included Quantitative Myasthenia Gravis (QMG) responders. Although for the subanalysis, only data from patients with AChR-Ab+ who received a stable dose of at least 1 gMG treatment were used. The outcomes were analyzed in the analysis were conducted by Zelen Exact test for homogeneous odds ratio between sex subgroups.

Efgartigimod, a human IgG1 antibody Fc-fragment, blocks the neonatal Fc receptor and reduces IgG autoantibody levels. The treatment was originally approved in December 2021 based on significant findings from ADAPT. In the original analysis, the agent was shown to be well-tolerated and efficacious, meeting the primary end point of improvement in MG-ADL scores relative to placebo (67.7% vs 29.7%; P <.0001). Additionally, 40.0% of efgartigimod-treated AChR-Ab+ patients achieved minimal or no symptoms compared with 11.1% treated with placebo.2

A list of secondary end points that demonstrated significant differences in the efgartigimod arm for AChR-Ab+ patients compared with placebo include MG-ADL responders in the overall population, as well as both AChR-Ab+ and AChR– patients (P <.0001), and time on trial in clinically meaningful improvement, defined as an MG-ADL improvement of 2 points or greater (P = .0001). Additional significant differences from efgartigimod group for AChR-Ab+ patients compared with placebo were fast onset of response on MG-ADL score, defined as onset observed in first 2 weeks (P = .0004). A sustained response was observed in 88.6% AChR-Ab+ patients who met the primary end point for at least 6 weeks, 56.8% for at least 8 weeks, and 34.1% for at least 12 weeks. Furthermore, 70.6% of AChR-Ab+ patients received a second treatment cycle, compared to only 25.6% of placebo patients.3,4

Of those in the treatment group 77% (n = 65) experienced treatment-emergent adverse events (AEs), while 84% (n = 70) of the placebo group did. The most frequent AEs reported were headache (efgartigimod: 29% [n = 24]; placebo: 28% [n = 23]) and nasopharyngitis (efgartigimod: 12% [n = 10]; placebo: 18% [n = 15]). Five percent (n = 4) of efgartigimod-treated patients and 8% (n = 7) patients in the placebo group had a serious AE, and each group had 3 patients (4%) discontinue treatment during the study.3

In a similar post analysis of ADAPT, efgartigimod was consistently effective when grouping patients by clinical characteristics such as time from diagnosis, thymectomy status, and concomitant medications.5 These findings were presented at the 2023 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference, held March 19 to 22, in Dallas, Texas, by senior investigator James Howard, MD, FAAN, Distinguished Professor of Neuromuscular Disease and chief of the Neuromuscular Disorders Section at the University of North Carolina School of Medicine. In the analysis, responder status was defined as at least 2-point improvement on MG-ADL or at least 3-point improvement on Quantitative Myasthenia Gravis (QMG) scores.

The post hoc analysis showed that with nonthymectomized patients, 85.0% (17 of 20) on efgartigimod achieved responder status vs 32.4% (11 of 34) of those on placebo.5 An even greater between-group difference was seen for concomitant medications, as 84.6% (11 of 13) of those on efgartigimod while only receiving concomitant acetylcholinesterase inhibitors achieved responder status vs 16.7% of those on placebo (difference, 67.9%; 95% CI, 32.3-100.0). For those who received any corticosteroid, 63.0% (29 of 46) of patients on efgartigimod were responders compared with 29.4% (15 of 51) on placebo (difference, 33.6; 95% CI, 14.9-52.4). Results for other subgroups, along with the proportion of QMG responders, also favored efgartigimod.

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REFERENCES
1. Hoffmann S, Zhao S, Callewaert F, Schoppe S. Gender-specific analysis of efgartigimod efficacy in patients with gMG: Subanalysis of the randomized phase3 ADAPT trial. Presented at: EAN 2023. July 1-4, 2019; Budapest, Hungary. EPO-055.
2. FDA Approves New Treatment for Myasthenia Gravis. News release. FDA. December 17, 2021. Accessed July 10, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-myasthenia-gravis
3. Howard JF, Bril V, Vu T, et al. Safety, efficacy, and tolerability of efgartigimod in patients with generalised myasthenia gravis (ADAPT): a multicentre, randomised, placebo-controlled, phase 3 trial. Lancet Neurol. 2021;20(7):526-536. doi:10.1016/S1474-4422(21)00159-9
4. Argenx announces positive topline results from phase 3 ADAPT trial of efgartigimod in patients with generalized myasthenia gravis. News release. Argenx. Published May 26, 2020. Accessed July 10, 2023. globenewswire.com/news-release/2020/05/26/2038308/0/en/argenx-Announces-Positive-Topline-Results-from-Phase-3-ADAPT-Trial-of-Efgartigimod-in-Patients-with-Generalized-Myasthenia-Gravis.html
5. Ritt E, Bril V, Vu T, et al. Efgartigimod demonstrates consistent improvements in generalized myasthenia gravis across patient subgroups, including early in diagnosis. Presented at: MDA 2023; March 19-22; Dallas, TX. Abstract 134