New interim data from the open label extension (OLE) of the ADAPT-SC+ trial (NCT04818671) assessing a subcutaneous (SC) version of efgartigimod (Argenx) PH20 demonstrated improvements in daily function in treated patients with generalized myasthenia gravis (gMG). These findings suggest multiple cycles of the treatment were well tolerated and showed strong efficacy, which were consistent with the results observed in using the intravenous (IV) formulation in the ADAPT/ADAPT+trial (NCT03669588).1
Since March 2022, 164 patients received at least 1 dose of efgartigimod PH20 SC, with an average of approximately equal to 3 treatment cycles over a mean study duration of 170 days (SD, 59), resulting in 72 patient-years of observation. In the first cycle, at week 4, investigators observed a –4.0 score (SE, 0.25) reduction in the Myasthenia Gravis Activities of Daily Living (MGADL) total score from cycle baseline, with consistent and repeatable improvements observed by investigators in subsequent cycles.
Clinical Takeaway
- Efgartigimod PH20 subcutaneous treatment in the ADAPT-SC+ trial demonstrated consistent improvements in daily function for myasthenia gravis patients, with well-tolerated cycles of administered treatment.
- Patients who completed previous trials and received efgartigimod IV were eligible for the ongoing ADAPT-SC+ trial, which showed efficacy similar to the intravenous treatment.
- The most common adverse events were mild or moderate, including injection site erythema, headache, and COVID-19, which did not lead to treatment discontinuation and decreased in incidence with subsequent cycles.
These findings were presented at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) meeting, held November 1-4, in Phoenix, Arizona, by lead author Yuebing Li, MD, PhD, a neurologist in the neuromuscular center at the Cleveland Clinic, and colleagues. Patients who completed ADAPT-SC (NCT04735432) or who were enrolled in the efgartigimod IV OLE ADAPT+ were eligible also for the ongoing OLE, ADAPT-SC+ trial. In the OLE, efgartigimod PH20 SC 1000 mg was given to patients in cycles of 4 weekly injections. The subsequent cycles were performed at least 28 days from the last dose based on clinical evaluation and then MGADL score evaluated clinical efficacy.
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In this analysis, investigators noted that adverse events (AEs) were predominantly mild or moderate. The most common AEs were injection site erythema (25.6%), headache (15.2%), and COVID-19 (11.6%). Patients who had site reactions were also mild or moderate in severity, did not lead to any discontinuation of treatment, and reduced in the incidence with subsequent cycles.
In the phase 3 ADAPT-SC study, SC efgartigimod PH20 met its primary end point of total IgG reduction from baseline at day 29, while showing statistical noninferiority to the FDA approved IV efgartigimod afla-fcab (Vyvgart) formulation.2 In a study population of 110 participants, the subcutaneous formulation was associated with a mean total reduction in IgG of 66.4% at day 29 compared with 62.2% seen with the IV formulation (P <.0001 for noninferiority). These results were consistent across the overall study cohort and were no different between patients with or without acetylcholine receptor (AChR) antibodies.
Of the total patients, all had a confirmed gMG diagnosis and a MG-ADL total score of at least 5 with greater than 50% of the total score attributed to nonocular symptoms, at both screening and baseline. Patients were on a stable dose of at least 1 gMG treatment prior to randomization into ADAPT-SC—including acetylcholinesterase inhibitors, corticosteroids, or nonsteroidal immunosuppressive drugs—and were required to remain on that dose throughout the trial. Participants were randomized 1:1 to either subcutaneous or IV efgartigimod for 1 treatment cycle consisting of 4 doses at weekly intervals. The total study lasted approximately 12 weeks, including 7 weeks of follow-up post treatment.
Supplementary key secondary end points were also met, according an Argenx announcement, and the efficacy results were consistent in ADAPT of the IV formulation.2 On the MG-ADL scores, 69.1% of those treated with the subcutaneous form were deemed responders, having an at least 2-point improvement for 4 consecutive weeks. Additionally, 65.5% of those treated with the new formulation were responders on the Quantitative Myasthenia Gravis (QMG) scoring, having displayed an at least 3-point improvement on the QMG score for a minimum of 4 consecutive weeks. As well, the observations of onset of effect and minimal symptom expression—defined as an MG-ADL score of 0 or 1—were also consistent with ADAPT findings.
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REFERENCES
1. Li Y, Howard JF Jr, Li G, et al. Long-Term Safety, Tolerability, and Efficacy of Subcutaneous Efgartigimod PH20 in Patients With Generalized Myasthenia Gravis: Interim Results of the ADAPT-SC+ Study. Presented at: American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) meeting; November 1-4, 2023; Phoenix, AZ. Abstract 222.
2. Argenx Announces Positive Topline Phase 3 Data From ADAPT-SC Study Evaluating Subcutaneous Efgartigimod for Generalized Myasthenia Gravis. News release. March 22, 2022. Accessed October 31, 2023. https://www.businesswire.com/news/home/20220321005941/en/argenx-Announces-Positive-Topline-Phase-3-Data-From-ADAPT-SC-Study-Evaluating-Subcutaneous-Efgartigimod-for-Generalized-Myasthenia-Gravis
