New Study to Test Subcutaneous Efgartigimod PH20 in Juvenile Myasthenia Gravis

Jamie H. Aldridge, PhD

(Credit: LinkedIn)

At the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific conference, held March 16-19 in Dallas, Texas, a poster presentation highlighted the design of a new study (NCT06392386) testing subcutaneous efgartigimod coformulated with recombinant hyaluranidase (PH20 SC; Vyvgart; Argenx) in juvenile patients with myasthenia gravis (MG), the most common form of pediatric MG.¹

The study, which aims to confirm the age-appropriate dose of efgartigimod PH20 SC, will recruit at least 12 patients, aged 2-17 with a confirmed diagnosis of Myasthenia Gravis Foundation of America class II, III, or IVa. Spanning a total of 14 weeks, the study includes a 2-week screening period, 4-week treatment period, and 8-week follow-up period testing 4 once-weekly injections of efgartigimod PH20 SC. The hope is that results from this study will help address an unmet need and provide additional flexibility for the treatment of pediatric patients with generalized MG.

Led by Jamie H. Aldridge, PhD, an associate medical director of neurology at Argenx, the trial test several pharmacokinetic (PK), pharmacodynamic (PD) measures, as well as safety, tolerability, immunogenicity, and clinical effects. Some of the scales used include Myasthenia Gravis Activities of Daily Living (MG-ADL), Quantitative Myasthenia Gravis (QMG) score, EuroQoL 5 Dimensions Youth (EQ-5D-Y) score, and Neuro-QoL Pediatric Fatigue score. In addition, the study will also test change in Clinical Global Impression of Improvement as well as changes in protective antibody titers to vaccines.

The open-label study uses a staggered design, with the older population (12-17 years of age) beginning first. This study excludes patients who are pregnant or lactating, those with worsening muscle weakness from infection or medication, or a lack of response to plasma exchange. Additional exclusions include recent live vaccinations, thymectomy within three months, certain untreated malignancies, active infections (e.g., Hepatitis B, HIV, SARS-CoV-2), or conditions that could interfere with assessments. Patients with hypersensitivity to the study drug, a history of substance abuse, or participation in another clinical trial are also excluded.

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The subcutaneous formulation of efgartigimod was approved in mid-2023 as a 1008-mg fixed dose administered over 30 to 90 seconds in cycles of once-weekly injections for 4 weeks. The decision to approve the new formulation in adults with gMG was based on data from the phase 3 ADAPT-SC study (NCT04735432), which evaluated the noninferiority noninferiority of the PK profile effect of subcutaneous efgartigimod as compared with the previously approved intravenous (IV) administration. ADAPT-SC, a trial that featured 110 individuals with gMG, met its primary end point of change in total immunoglobulin (IgG) reduction over a 29-day period.^2,3

The IV formulation of efgartigimod, the first approved of the 2 formulations, is also currently being study in patients with juvenile MG. Known as ADAPT Jr, the study (NCT04833894), the trial includes an 8-week dose-confirmatory period (Part A) followed by a treatment response-confirmatory period (Part B) to test PK, PD, safety, and efficacy. In the study, patients are between the ages of 2 and 18, must show an inadequate response to prior therapies, be on stable gMG treatment, and test positive for anti-acetylcholine (AChR) antibodies.⁴

ADAPT Jr excludes participants with MGFA class I, IVb, or V and females who are pregnant, lactating, or planning pregnancy during or shortly after the trial. Medical conditions such as uncontrolled infections, interfering autoimmune diseases, recent major surgeries, or conditions complicating myasthenia gravis assessment are disqualifying. Exclusion extends to participants with malignancies not cured for at least three years (with exceptions like skin cancers or in situ carcinomas), worsening weakness due to medications, or a lack of response to plasma exchange. Those who recently received live vaccines, thymectomies, or specific investigational therapies are also excluded, as are individuals with active viral infections, low immunoglobulin levels, or a history of hypersensitivity to the study drug.

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REFERENCES
1. Aldridge J, Schwaede A, Kuntz NL, et al. Study Design of Subcutaneous Efgartigimod PH20 in Juvenile Generalized Myasthenia Gravis. Presented at: 2025 MDA Clinical & Scientific Conference; March 16-19. Dallas, TX. ABSTRACT P356
2. argenx Announces U.S. Food and Drug Administration Approval of VYVGART Hytrulo (efgartigimod alfa and hyaluronidase-qvfc) Injection for Subcutaneous Use in Generalized Myasthenia Gravis. News release. Argenx. June 20, 2023. Accessed March 13, 2025. https://www.globenewswire.com/news-release/2023/06/20/2691658/0/en/argenx-Announces-U-S-Food-and-Drug-Administration-Approval-of-VYVGART-Hytrulo-efgartigimod-alfa-and-hyaluronidase-qvfc-Injection-for-Subcutaneous-Use-in-Generalized-Myasthenia-Grav.html
3. Argenx Announces Positive Topline Phase 3 Data From ADAPT-SC Study Evaluating Subcutaneous Efgartigimod for Generalized Myasthenia Gravis. News release. March 22, 2022. Accessed March 13, 2025. https://www.argenx.com/news/argenx-announces-positive-topline-phase-3-data-adapt-sc-study-evaluating-subcutaneous
4. Evaluating the Pharmacokinetics, Pharmacodynamics, and Safety of Efgartigimod Administered Intravenously in Children with Generalized Myasthenia Gravis (ADAPT Jr). Clinicaltrials.gov. Updated October 30, 2024. Accessed March 13, 2025. https://clinicaltrials.gov/study/NCT04833894