FDA Approves Argenx’s Vyvgart for Generalized Myasthenia Gravis

The U.S. Food and Drug Administration has approved Argenx’s Vyvgart for the treatment of generalized myasthenia gravis in adult patients who are anti-acetylcholine receptor antibody positive, making it the first-and-only FDA-approved neonatal Fc receptor blocker.

Photo: Tim Van Hauwermeiren, CEO of Argenx.

Generalized myasthenia gravis (gMG) is a rare and chronic autoimmune disease where IgG autoantibodies disrupt communication between nerves and muscles, causing debilitating and potentially life-threatening muscle weakness. Approximately 85 percent of people with MG progress to gMG within 24 months, where muscles throughout the body may be affected. Patients with confirmed anti-acetylcholine receptor (AChR) antibodies account for approximately 85 percent of the total gMG population.

“The approval of Vyvgart represents many achievements: our first approved product; the first-and-only FDA-approved neonatal Fc receptor blocker; and the first approved therapy designed to reduce pathogenic IgGs, an underlying driver of gMG,” said Tim Van Hauwermeiren, CEO of Argenx.

Vyvgart is a human IgG1 antibody fragment that binds to Fc receptor, resulting in the reduction of circulating immunoglobulin G (IgG) antibodies. The action of AChR autoantibodies at the neuromuscular junction is a key driver of gMG2.

The approval of Vyvgart is based on results from the global phase 3 ADAPT trial, which were published in the July 2021 issue of The Lancet Neurology. The ADAPT trial met its primary endpoint, demonstrating that significantly more anti-AChR antibody positive gMG patients were responders on the MG-ADL scale following treatment with Vyvgart compared with placebo (68 percent vs. 30 percent). Responders were defined as having at least a two-point reduction on the MG-ADL scale sustained for four or more consecutive weeks during the first treatment cycle.

There were additionally significantly more responders on the Quantitative Myasthenia Gravis (QMG) scale following treatment with Vyvgart compared with placebo (63 percent vs. 14 percent). Responders were defined as having at least a three-point reduction on the QMG scale sustained for four or more consecutive weeks during the first treatment cycle.

Vyvgart had a demonstrated safety profile in the ADAPT clinical trial. The most common adverse events in ADAPT were respiratory tract infection (33 percent vs 29 percent placebo), headache (32 percent vs 29 percent placebo), and urinary tract infection (10 percent vs. 5 percent placebo).

“People living with gMG have been in need of new treatment options that are targeted to the underlying pathogenesis of the disease and supported by clinical data,” said James Howard Jr., professor of Neurology, Medicine and Allied Health, Department of Neurology, The University of North Carolina at Chapel Hill School of Medicine and principal investigator for the ADAPT trial. “Today’s approval represents an important new advance for gMG patients and families affected by this debilitating disease. This therapy has the potential to reduce the disease burden of gMG and transform the way we treat this disease.” 

Argenx has reached agreement in principle with various national and regional payers to structure value-based agreements. The company is also launching a program to connect patients and clinicians to personalized support throughout their treatment journey.

“Generalized myasthenia gravis imposes a significant lifestyle and treatment burden on patients, families, and the overall healthcare system. This autoimmune disease affects each patient differently which can create variability in dosing and the resulting cost per patient,” said Steve Miller, executive vice president and chief clinical officer at Cigna Corp. “The approval of Vyvgart promises to address a treatment gap for patients suffering from this disease. Argenx has put forth an innovative, value-based approach to contracting that will help payers with cost predictability as they face the challenge of ensuring real-world dosing remains affordable.”

Marketing Authorization applications for efgartigimod for the treatment of gMG are currently under review with Japan’s Pharmaceuticals and Medical Devices Agency and the European Medicines Agency, with anticipated decisions from each agency in the first quarter and second half of 2022, respectively.

Argenx has an exclusive partnership agreement with Zai Lab for the development and commercialization of efgartigimod in Greater China. Zai Lab is on track to file for approval in Greater China by mid-2022. Under the terms of the strategic agreement with Zai Lab, Argenx will receive a $25 million milestone payment with this U.S. approval of Vyvgart. In addition, Argenx has an exclusive partnership with Medison for the commercialization of efgartigimod in gMG in Israel. Medison is on track to file for approval in Israel in the second quarter of 2022.

Author: Rare Daily Staff