James F. Howard Jr., MD, Distinguished Professor in the UNC Department of Neurology, was principal investigator of the promising phase 3 trial for the experimental drug efgartigimod.
Argenx, a Belgium pharmaceutical company, recently announced that The Lancet Neurology has published pivotal trial results from the Phase 3 ADAPT trial of efgartigimod, an FcRn antagonist, for the treatment of adults living with generalized myasthenia gravis (gMG). Efgartigimod is currently under review with the U.S. Food and Drug Administration (FDA) for the treatment of gMG with a Prescription Drug User Fee Act (PDUFA) target action date of December 17, 2021, and if approved, would be the first-and-only approved FcRn antagonist.
“Myasthenia gravis can have a devastating impact on a person’s life and independence, potentially affecting one’s ability to swallow, speak, walk and even breathe. In addition, each patient experiences the course of MG differently, which can make disease management unpredictable,” said James F. Howard Jr., MD, Distinguished of Neuromuscular Disease and professor of medicine, neurology and allied health at the UNC School of Medicine and principal investigator for the ADAPT trial. “In the ADAPT trial, we observed clinically meaningful improvements in the first two weeks of dosing in a majority of patients treated with efgartigimod. These results are important for the MG community and I am hopeful efgartigimod will provide a first-in-class targeted therapy that can be dosed in an individual way for people living with this chronic autoimmune disease.”
The ADAPT trial met its primary endpoint demonstrating significantly more acetylcholine receptor-antibody positive (AChR-Ab+) gMG patients were responders on the Myasthenia Gravis Activities of Daily Living (MG-ADL) score following treatment with efgartigimod compared with placebo (67.7% vs. 29.7%; p<0.0001). Responders were defined as having at least a two-point improvement sustained for four or more consecutive weeks on the MG-ADL score. Further 40% of patients treated with efgartigimod achieved minimal symptom expression defined as MG-ADL scores of zero (symptom free) or one, compared to 11.1% of patients who received placebo. Among AChR-Ab+ responders, 84.1% showed clinically meaningful improvement on the MG-ADL score within the first two weeks of treatment. The safety profile of efgartigimod was comparable to placebo.
After completing ADAPT, 90% of participants entered ADAPT-plus, an ongoing three-year open-label extension study evaluating the long-term safety and tolerability of efgartigimod. In total across ADAPT and ADAPT-plus, at least 118 patients have been on efgartigimod therapy for 12 months or more.
“The publication of the ADAPT results provides an exciting opportunity to share these data with the clinical community as we aim to introduce a new treatment option for gMG patients. gMG is a chronic, debilitating and potentially life-threatening disease where both the disease symptoms and side effects from current therapies can cause significant impairment on a person’s life. Wim Parys, M.D., chief medical officer of argenx. “Efgartigimod is currently under review with the FDA for the treatment of gMG, and if approved, we look forward to bringing this therapy to MG patients who are in great need of new treatment options.”
Phase 3 ADAPT Trial
The Phase 3 ADAPT trial was a randomized, double-blind, placebo-controlled, multi-center, global trial evaluating the safety and efficacy of efgartigimod in patients with gMG. A total of 167 adult patients with gMG in North America, Europe and Japan enrolled in the trial and were treated. Patients were eligible to enroll in ADAPT regardless of antibody status, including patients with AChR antibodies (AChR-Ab+) and patients where AChR antibodies were not detected. Patients were randomized in a 1:1 ratio to receive efgartigimod or placebo for a total of 26 weeks. ADAPT was designed to enable an individualized treatment approach with an initial treatment cycle followed by a variable number of subsequent treatment cycles. The primary endpoint was the number of AChR-Ab+ patients who achieved a response on the MG-ADL score defined by at least a two-point improvement for four or more consecutive weeks.
Efgartigimod is an investigational antibody fragment designed to reduce disease-causing immunoglobulin G (IgG) antibodies and block the IgG recycling process. Efgartigimod binds to the neonatal Fc receptor (FcRn), which is widely expressed throughout the body and plays a central role in rescuing IgG antibodies from degradation. Blocking FcRn reduces IgG antibody levels representing a logical potential therapeutic approach for several autoimmune diseases known to be driven by disease-causing IgG antibodies, including: myasthenia gravis (MG), a chronic disease that causes muscle weakness; pemphigus vulgaris (PV), a chronic disease characterized by severe blistering of the skin; immune thrombocytopenia (ITP), a chronic bruising and bleeding disease; and chronic inflammatory demyelinating polyneuropathy (CIDP), a neurological disease leading to impaired motor function.