Argenx Reports Positive Phase 3 Study Results for Experimental Myasthenia Gravis Therapy
May 26, 2020
Argenx reported positive topline data from the pivotal ADAPT trial in patients with generalized myasthenia gravis, which showed that treatment with its experimental therapy efgartigimod was safe, well tolerated, and met the primary endpoint.
The primary endpoint for the study was defined as percentage of responders having at least a two-point improvement for at least four consecutive weeks on the Myasthenia Gravis Activities of Daily Living (MG-ADL) score among acetylcholine receptor-antibody positive (AChR-Ab+) generalized myasthenia gravis (gMG) patients.
Myasthenia gravis (MG) is a rare and chronic autoimmune disease where IgG antibodies disrupt communication between nerves and muscles, causing debilitating and potentially life-threatening muscle weakness. More than 85 percent of people with MG progress to generalized MG (gMG) within 18 months, where muscles throughout the body may be affected, resulting in extreme fatigue and difficulties with facial expression, speech, swallowing and mobility. In more life-threatening cases, MG can affect the muscles responsible for breathing. Patients with confirmed AChR antibodies account for 80 to 90 percent of the total gMG population. There are approximately 65,000 people in the United States and 20,000 people in Japan living with the disease.
Efgartigimod is a first-in-class 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; pemphigus vulgaris, a chronic disease characterized by severe blistering of the skin; immune thrombocytopenia, a chronic bruising and bleeding disease; and chronic inflammatory demyelinating polyneuropathy, a neurological disease leading to impaired motor function.
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. Enrolled patients had a confirmed gMG diagnosis and an MG-ADL total score of five or greater. Patients were on a stable dose of at least one gMG treatment prior to randomization, including acetylcholinesterase inhibitors, corticosteroids or nonsteroidal immunosuppressive drugs, and were required to remain on that stable dose throughout the primary trial. Patients were eligible to enroll 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 as part of the primary trial, which was designed to enable an individualized treatment approach with an initial treatment cycle followed by a variable number of subsequent treatment cycles. Treatment cycles consist of four infusions of efgartigimod or placebo at weekly intervals. Retreatment with additional treatment cycles was initiated according to clinical response. 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. After the 26-week primary trial, patients were eligible to roll over into an open-label extension study.
The positive data showed that 67.7 percent of AChR-Ab+ patients treated with efgartigimod achieved the primary endpoint compared with 29.7 percent on placebo; 63.1 percent of AChR-Ab+ patients treated with efgartigimod had at least a three-point improvement on the Quantitative Myasthenia Gravis (QMG) score compared to 14.1 percent on placebo for at least four consecutive weeks; and 40 percent of treated patients achieved minimal symptom expression defined as MG-ADL scores of 0 (symptom free) or 1, compared to 11.1 percent treated with placebo. Efgartigimod was well tolerated with a safety profile that was comparable to placebo.
Based on these results, Argenx plans to submit a Biologics License Application to the U.S. Food and Drug Administration by the end of 2020.
“The data showed that efgartigimod drove fast and deep responses, including in a proportion of patients who achieved minimal or no symptoms after treatment. In addition, we saw responses that lasted beyond eight or 12 weeks, supporting our plans to offer individualized dosing schedules that are purpose-fit to the variability in disease course that gMG patients experience,” said Wim Parys, chief medical office of Argenx.
Detailed data from the trial will be submitted for presentation at a future medical meeting.
Author: Rare Daily Staff
Sign up for updates straight to your inbox.