Efgartigimod (ARGX-113) developed by the Dutch biotechnology company Argenx, is an investigational therapy to treat autoimmune diseases. The therapy received orphan drug status in both the U.S. and Europe. The company plans to submit an application to the U.S. Food and Drug Administration (FDA) by the end of 2020 for efgartigimod to treat generalized myasthenia gravis.
How does efgartigimod work?
Antibodies are proteins that the immune system produces in response to foreign molecules invading the body. Also known as immunoglobulins, they fall into five classes: IgG, IgA, IgM, IgD, and IgE. Each class acts slightly differently and responds to different threats. Most antibodies in the blood and fluid that surrounds tissues and cells belong to the IgG class.
In MG, the IgGs that the body produces mistakenly attack portions of the neuromuscular junction (the point at which nerve cells meet muscle cells). Many patients with MG have autoantibodies against the acetylcholine receptor — a protein that binds to the neurotransmitter acetylcholine when it has been released from the nerve cell ending in response to a signal from the brain to relay that information to the muscles. Normally, the binding of acetylcholine to the acetylcholine receptor signals the muscle to contract. However, because the immune system attacks the acetylcholine receptors in MG, acetylcholine cannot bind to them efficiently and the nerve cells cannot send a strong signal to the muscles.
Each antibody has two Fab regions and one Fc region. The Fc region provides the binding site for receptors on the surface of B-cells (the type of immune cell that produces most antibodies), as well as for other antibodies. Efgartigimod is the Fc portion of an antibody that Argenx’ scientists have modified to increase its affinity for IgGs beyond that of normal antibodies. As a result, efgartigimod binds to IgG antibodies, including those that cause MG symptoms. Efgartigimod is not specific for antibodies that cause MG, however. Therefore, the medication also will act on antibodies produced by the immune system in response to infections.
Doctors administer efgartigimod as an infusion into the bloodstream.
Efgartigimod in clinical trials
In Phase 1 studies, researchers demonstrated that efgartigimod had favorable safety and tolerability with different doses and dosing regimens. They also showed that the treatment led to promising reductions in the levels of disease-causing IgG.
A Phase 2 study (NCT02965573) to assess the safety, efficacy, and pharmacokinetics (movement in the body) of efgartigimod in MG patients with generalized muscle weakness has been completed. Researchers administered efgartigimod in addition to patients’ current treatment, which included cholinesterase inhibitors, corticosteroids, or immunosuppressants. The results showed that 75% of patients treated with efgartigimod had clinically and statistically significant improvements through at least six weeks, compared to 25% of patients taking placebo. Researchers reported no severe adverse reactions (side effects).
A Phase 3 clinical trial (NCT03669588) called ADAPT evaluated the safety and effectiveness of efgartigimod in 167 adults with MG. The trial enrolled participants both with and without antibodies against acetylcholine receptors (AChR). They received either efgartigimod or a placebo, in addition to their current standard treatments, for 26 weeks. The goal of the study was to assess the percentage of anti-AChR positive patients responding to treatment. Researchers defined “improvement” as at least a two-point improvement for at least four consecutive weeks in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score.
Argenx reported that this goal was met, with significantly more anti-AChR positive patients on efgartigimod experiencing clinically meaningful improvements on their symptom severity scores (67.7%) compared with those on the placebo (29.7%). More MG patients on efgartigimod reported minimal to no symptoms compared to those on placebo (40% vs. 11.1%). Patients tolerated the therapy well, with the safety profiles of efgartigimod comparable to those of the placebo.
Ongoing clinical trials
After completing ADAPT, most participants (90%) entered an open-label extension study called ADAPT-Plus (NCT03770403). During this study, all participants will receive active treatment for up to three years. Researchers expect to complete this extension trial in 2023.
Because efgartigimod interacts with the immune system, it may make patients more susceptible to infections.
Last updated: Aug. 4, 2020
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