Long-Term Efficacy and Safety of Efgartigimod for Treatment of Generalized Myasthenia Gravis With Antibodies to Acetylcholine Receptors

Efgartigimod (Vyvgart; Argenx, Boston, MA) was recently approved for the treatment of antiacetylcholine receptor (AChR) antibody-positive generalized myasthenia gravis (gMG) in adults. In the phase 3 ADAPT (NCT03669588) study of efgartigimod vs placebo gMG symptoms responded in 68% (44/65) vs 30% (19/64) after 1 cycle of weekly treatments for 4 weeks. Response to treatment was defined as a 2 or more-point reduction on the Myasthenia Gravis - Activities of Daily Living (MG-ADL) scale for at least 4 consecutive weeks. 

Retreatments could be given 5 weeks or more after the last treatment cycle only if participants symptoms led to MG-ADL scores within 2 points of a participant's baseline score. Over 50% of participants had response to a treatment cycle lasting 8 weeks or more. Approximately 17% had a 12-week maintenance of response, and approximately 8% did not need a second cycle of treatment for the full 26-week double-blind period. 

In ADAPT+, the open-label extension study, analysis of treatment frequency suggests that most patients will need 5 treatments/year. During the open-label trial, participants could be retreated every 5 weeks if it was clinically warranted, regardless of MG-ADL score, and during the trial, this was lowered to 4 weeks. Notably, individual's response to treatment was consistent across treatment cycles. 

Principal investigator of the ADAPT+ study, James F. Howard Jr, MD, professor of Neurology, Medicine and Allied Health, Department of Neurology, The University of North Carolina at Chapel Hill School of Medicine said, "Seeing these different response groups suggest that we may be able to deliver more precise management of gMG with Vyvgart, improving symptoms and quality of life, while substantially decreasing the frequency and burden of treatment. We now have tools to provide choices that can be adapted to therapeutic needs of individuals and achieve efficacy much similar and sometimes better than other options for gMG with a much narrower side effect profile."

Efgartigimod is administered as an intravenous infusion and clinical trials of a subcutaneous formulation are underway. Efgartigimod inhibits the recycling of IgG, which results in more lysosomal destruction of IgG and overall lower levels of IgG. This preserves antibody response and production in both the innate and adaptive immune processes. 

Of those in the double-blind study, 91% (151/167) continued into the open-label extension. The mean  open-label follow-up period was 363 days (range 50-586 days). The most common adverse events in those treated with efgartigimod throughout both phases or placebo then efgartigimod were headache (15.1%/30.3%), nasopharyngitis (8.2%/13.6%). Infusion reactions occurred uncommonly and were more frequent in those treated with placebo. There were 5 deaths from acute myocardial infarction, COVID-19 pneumonia/septic shock, malignancy, bacterial pneumonia/MG crisis, and unknown cause; none were considered treatment related.