Vyvgart Phase 3 Extension Study Data Affirm Long-Term Safety, Efficacy in gMG

Researchers have published interim results on the long-term safety and efficacy of efgartigimod (Vyvgart) in generalized myasthenia gravis (gMG).

Details from the final interim data analysis of the ADAPT+ study, posted in Frontiers of Neurology, confirm previous findings seen with efgartigimod in the rare neuromuscular autoimmune disease. These published findings from the open-label, multicenter extension phase of the pivotal ADAPT study include data from 145 patients who received at least 1 dose of efgartigimod as of January 2022. Efgartigimod gained FDA approval for the treatment of gMG at the end of 2021.

Analyzing clinical data | Image Credit: sdecoret - stock.adobe.com

“The ADAPT and ADAPT+ studies treated a broad gMG patient population, including those in early and late stages of the disease course, with mild to moderate disease severity, and regardless of autoantibody status (AChR-Ab+ [acetylcholine receptor–antibody positive] and AChR-Ab− [acetylcholine receptor–antibody negative] participants),” noted the researchers, adding, “Additionally, the participants were receiving a broad range of commonly used MG treatments, including a cohort receiving only AChE [acetylcholinesterase] inhibitors.”

After a mean duration of approximately 1.5 years, patients received as many as 17 cycles of treatment. Each treatment cycle consisted of 4 once-weekly intravenous infusions. Similar to the ADAPT study, the ADAPT+ study used an individualized approach to dosing, with the frequency of treatment cycles dependent on the clinical evaluation of each patient.

A significant amount of patients had clinical improvements in function and muscle strength that were considered above clinically meaningful improvement (CMI) thresholds, and some patients saw CMI, based on 2 MG-related scoring systems, as quickly as 1 week after their first infusion. The researchers noted the limited number of patient assessments, occurring once a week for 4 weeks, followed by every 30 days for year 1, and every 90 days in the following 2 years. This limited assessment, explained the group, may resulting in not being able to capture maximum clinical improvements and other measures.

Across all patients in the extension study, treatment-emergent adverse events (TEAEs) were reported in 84.8% (n = 123) of patients. Headache (24.8%), COVID-19 (15.2%), and nasopharyngitis (13.8%) were the most frequently reported TEAEs. Repeated cycles of efgartigimod did not yield an increase in existing or new AEs.

“Similar to results from the ADAPT study, the majority of infections observed with long-term efgartigimod treatment in ADAPT+ were mild or moderate in severity. Although not definitive, these data are reassuring and reflect efgartigimod’s mechanism of action of selective IgG [immunoglobulin G] reduction, which leads to substantial but incomplete IgG reduction without altering other Immunoglobulins,” explained the researchers. “FcRn [neonatal Fc receptor] blockade does not inhibit IgG production, therefore allowing the immune system to mount a cellular and humoral response upon antigen challenge; in ADAPT+, antigen-specific IgG responses were observed in participants who received T-cell–dependent and T-cell–independent vaccines, indicating they retained the ability to mount an immune response.”

Twelve (8.3%) patients discontinued treatment due to a TEAE, and serious TEAEs were reported in 23.4% of patients. Five serious and fatal TEAEs occurred, although they were deemed not related to efgartigimod by the investigatosr.

According to the researchers, reductions in IgG, IgG subtypes, and AChR antibodies seen in ADAPT+ were consistent with those seen in the ADAPT study.

Serum albumin levels also were not decreased, and increases in total cholesterol or low-density lipoprotein were not observed. The researchers also found no clinically relevant changes in hematology or chemistry parameters, nor changes in vital sign parameters.

Reference

Howard JF, Bril V, Karam C, et al. Long-term safety, tolerability, and efficacy of efgartigimod (ADAPT+): interim results from a phase 3 open-label extension study in participants with generalized myasthenia gravis. Front Neurol. Published online January 16, 2024. doi:10.3389/fneur.2023.1284444