Generalized myasthenia gravis (gMG) is a rare neuromuscular disorder that causes moderate to severe muscle weakness, often accompanied by fatigue. The condition disrupts daily life, making it difficult for patients to work, socialize, or carry out routine tasks.
In recent years, new FDA-approved treatments have become available for one of the most common forms of gMG. But until now, researchers knew little about how one of these therapies, efgartigimod, worked for patients with other subtypes.
James Howard, MD
A new clinical trial led by researchers at the UNC School of Medicine shows that efgartigimod, an infusion therapy developed by argenx, is safe and effective for all subtypes of gMG. Results from the largest trial of its kind were presented at the Annual Scientific Session of the Myasthenia Gravis Foundation of America.
"The results of this study confirm that this medication now has the potential to be a targeted, effective, safe, and necessary treatment for patients, regardless of autoantibody status," said James F. Howard Jr., MD, an expert on myasthenia gravis at the UNC School of Medicine and principal investigator on the trial. "This is a critical advancement in the management of this debilitating and unpredictable disease for patients with limited treatment options."
Following results from the clinical trial, the drug maker is now looking to expand access of the FDA-approved medication to thousands more patients who are living with gMG.
Subtypes of Generalized Myasthenia Gravis
Generalized myasthenia gravis occurs when antibodies produced by an abhorrent immune system target and "attack" the junction where nerves communicate with muscles, producing fluctuating muscle weakness and exertional fatigue.
Artist's rendition of the myasthenic neuromuscular junction. Credit: JF Howard Jr.
Efgartigimod reduces the harmful antibodies that interfere with nerve-muscle communication. The most common subtype, AChR antibody-positive gMG, is caused by antibodies against acetylcholine receptors, the main receptors that control voluntary muscle movement.
However, there are three other subtypes of the disease, which are classified based on the presence or lack thereof of specific antibodies in the blood:
- MuSK-positive gMG
- Patients have antibodies that attack muscle-specific kinase (MuSK), a receptor needed to form and maintain the junction between nerves and muscles.
- LRP4-positive gMG
- Patients have antibodies that attack low-density lipoprotein receptor-related protein 4 (LRP4), another receptor critical for the nerve-muscle connection.
- Triple seronegative gMG
- Patients have no detectable antibodies against AChR, MuSK, or LRP4.
- These patients often face a higher disease burden and have historically been excluded from clinical studies, leaving significant unmet medical needs.
ADAPT SERON Study
To help determine the safety and efficacy of efgartigimod in other subtypes, researchers launched a new study: the ADAPT SERON study.
Howard, who previously led the ADAPT and ADAPT+ trials that led to approval of efgartigimod, returned as principal investigator for the Phase 3 study.
Participants were recruited from North America, Europe, China, and the Middle East. Patients received four weekly infusions of efgartigimod or placebo, followed by additional open-label treatment.
At the end of the trial, 119 patients treated with efgartigimod experienced significant improvements in quality of life, measured by the Myasthenia Gravis Activities of Daily Living (MG-ADL) score, which tracks speaking, swallowing, breathing, and limb strength.
Future Implications
Based on these results, argenx plans to submit a Supplemental Biologic License Application to the FDA to expand the efgartigimod label to include MuSK-positive, LRP4-positive, and triple seronegative gMG patients.
Data from the ADAPT SERON study was revealed at the Annual Scientific Session of the Myasthenia Gravis Foundation of America in San Francisco on Wednesday, October 29.
