Argenx’s lead candidate efgartigimod (ARGX-113) safely and effectively eases symptoms in people with generalized myasthenia gravis (gMG) who have acetylcholine receptors (AChR) autoantibodies, top-line data from a Phase 3 clinical trial show.
While most of the trial’s goals were focused on AChR-positive patients (the most common group in MG), clinical responses were also observed in those without such autoantibodies.
“These data are very encouraging as they show efgartigimod has potential to make a meaningful impact on daily living activities, and we are hopeful they will lead to a new treatment being available for the gMG community,” James F. Howard Jr., MD, the trial’s principal investigator, said in a press release. Howard is also a professor at the University of North Carolina at Chapel Hill School of Medicine.
Argenx plans to submit an application to the U.S. Food and Drug Administration (FDA) requesting regulatory approval for efgartigimod.
“Based on these data, we intend to submit a BLA [biologics license application] for efgartigimod to the FDA before the end of the year, taking us one step closer to potentially making efgartigimod available to patients in 2021,” said Wim Parys, MD, Argenx’s chief medical officer.
The immune system of people with myasthenia gravis mistakenly attacks AChR or other cell membrane proteins essential for nerve-muscle cell communication by producing immunoglobulin G (IgG) autoantibodies.
Efgartigimod is a lab-made antibody fragment designed to prevent the binding of such disease-causing autoantibodies to FcRn, a receptor involved in the recycling of IgG autoantibodies.
In this way, the therapy is thought to impair autoantibody recycling and promote their destruction and clearance within cells, ultimately lowering their levels in the blood.
Results from previous Phase 1 (NCT03457649) and Phase 2 (NCT02965573) trials showed that efgartigimod safely promoted a drop in autoantibody levels and led to fast and clinically meaningful reductions in disease severity.
The Phase 3 ADAPT trial (NCT03669588) evaluated the safety and effectiveness of efgartigimod in 167 adults with gMG, regardless of the presence of anti-AChR autoantibodies.
Participants, recruited at sites across Japan, North America, and Europe, were randomly assigned to either 10 mg/kg of efgartigimod or a placebo, infused directly into the bloodstream, for 26 weeks (about six months) in addition to their current standard treatments.
After an initial treatment cycle (four weeks of a single weekly infusion), patients received an individualized treatment approach with a variable number of subsequent cycles according to their clinical responses.
The trial’s main goal was to assess the percentage of AChR-positive patients responding to treatment, defined as those showing at least a two-point improvement on the Myasthenia Gravis Activities of Daily Living (MG-ADL) score for at least four consecutive weeks. MG-ADL is a patient-reported, eight-question survey that assesses MG symptom severity.
Secondary goals included assessing the percentage of AChR-positive patients showing at least a three-point improvement on the Quantitative MG (QMG) score for at least four consecutive weeks; fast MG-ADL-responders, response in the first two weeks, among AChR-positive patients; and MG-ADL-responders in the overall patient population. Duration of responses was also evaluated.
The trial met it primary goal, with significantly more AChR-positive patients treated with efgartigimod showing clinically meaningful MG-ADL improvements than those on a placebo: 67.7% vs. 29.7%.
Notably, 40% of efgartigimod-treated patients with anti-AChR antibodies achieved minimal or no symptoms, compared with 11.1% of those given a placebo.
Most treatment responses were durable, with 88.6% of AChR-positive patients showing a response for at least six weeks, 56.8% for at least eight weeks, and 34.1% for at least 12 weeks.
In addition, significantly more AChR-positive patients treated with efgartigimod had a fast response, and spent significantly more time showing clinically meaningful MG-ADL improvements than those on a placebo.
Efgartigimod was also superior to a placebo in the overall population, regardless of the presence of anti-AChR autoantibodies. Within AChR-negative patients, response rates were consistent with those in anti-AChR-positive patients, but responses to placebo were greater.
The therapy was well-tolerated, with a safety profile comparable with placebo. Argenx now plans to present detailed trial data at a future medical meeting.
“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,” Parys said.
After completing the trial, most participants (90%) entered an open-label extension study called ADAPT-Plus (NCT03770403), in which all will receive the treatment for up to three years.
In both the U.S. and in Europe, efgartigimod received orphan drug status, which is meant to help speed the therapy’s development and ensures marketing exclusivity for a period of time upon regulatory approval (seven years in the U.S., and 10 years in Europe).
Parys added that these data support Argenx’s confidence in the therapeutic potential of efgartigimod for other IgG-mediated autoimmune diseases, such as pemphigus vulgaris, immune thrombocytopenia, and chronic inflammatory demyelinating polyneuropathy. Clinical trials testing efgartigimod in such conditions are already underway.
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