Myasthenia gravis (MG) is an autoimmune illness of the neuromuscular junction that presents with localized or widespread voluntary muscle exhaustion and malaise. MG is a typical example of a B-cell–mediated dysfunction, with increased production of harmful antibodies aimed at blocking and eventually destroying the muscle receptor sites for acetylcholine (ACh). ACh is the predominant neurotransmitter of the parasympathetic nervous system, and its depletion impairs the functions of vital transmembrane proteins such as muscle-specific receptor tyrosine kinase, lipoprotein-related protein 4, and agrin in the postsynaptic membrane of the neurotransmitter junction. With fewer muscle locations accessible, nerve signal transmission is severely restricted. This also results in the weariness of the ocular, bulbar, axial, respiratory, and limb muscles1.
It has been brought to light that MG is the most prevalent disease of the neuromuscular junction, exhibiting highly polymorphic clinical manifestations with an occurrence ranging from 4.1 to 30 cases per million person-years and an overall prevalence between 150 and 200 cases per million, a significant proportion of which are anti-acetylcholine receptor (AChR) antibody positive1. The increasing depletion of AChR from the postsynaptic membrane is caused by complement-mediated damage and an increase in the rate of AChR turnover. In light of this, there is an unmet medical need for a focused and effective long-term therapy option for MG, which continues to serve as a paradigm for autoantibody-mediated disorders.
In a report that was published by Argenx, a well-known global immunology company, the approval of VYVGARTTM (Efgartigimod alfa-fcab) as an adjunct to standard treatment for adult patients with generalized myasthenia gravis (gMG) who are positive for anti-AChR antibodies was reported. The approval was granted by the European Commission (EC). All 27 members of the European Union (EU), including Iceland, Norway, and Liechtenstein, are now covered by the decision to allow this drug’s commercial authorization2. In the class of neonatal Fc receptor antagonists, Efgartigimod (Efgartigimod alfa-fcab, VYVGART) is the first of its kind. The neonatal Fc receptor particularly prolongs the half-life of immunoglobulin G (IgG) by blocking their lysosomal degradation, thereby bringing them back into circulation3. Therefore, VYVGART (Efgartigimod alfa-fcab) offers a tremendous opportunity to help combat MG due to its ability to bind to these neonatal Fc receptors, subsequently reducing levels of IgG. In addition to the other pathogenic autoantibodies of this isotype, it also operates without altering other immunoglobulin levels. The acceptance of VYVGART by the EC was precipitated by the positive findings of the international phase 3 ADAPT trial, which was conducted using a randomized, double-blind, and placebo-controlled design.
Regardless of the presence or absence of anti-AChR antibodies, patients with gMG older than 18 years of age who had a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 5 (>50% nonocular) and were taking stable doses of at least 1 MG treatment (eg, corticosteroids, acetylcholinesterase inhibitors, and/or NSISTs) were qualified to participate in the study. They were randomly assigned to receive either Efgartigimod (10Â mg/kg) or a placebo intravenously 4 times every cycle. Primarily, this study aimed to know whether those with anti-AChR antibodies, which also had a valid baseline MG-ADL assessment, could be successfully treated with this medication without compromising safety or tolerability. The secondary endpoints included testing the efficacy of the drug.
The result of this trial indicates that Efgartigimod was found to be safe, efficacious, and well-tolerated in all 167 patients, with no adverse effects or alterations in vital signs or ECG findings observed. Seventy-five percent of patients treated with Efgartigimod had quick and long-lasting disease improvement, as evidenced by assessment using all 4 efficacy scales; total IgG and anti-AChR autoantibody levels declined considerably in all patients4.
Therefore, considering the previous study results, it can be concluded that VYVGART (Efgartigimod alfa-fcab) can offer an innovative, groundbreaking approach to the effective treatment of MG. Through its function, it can render a transient decrease in the levels of pathogenic IgG autoantibodies. The development of VYVGART (Efgartigimod alfa-fcab) as the pioneering recombinant antibody-based therapy for highly selective IgG depletion has broadened the medication’s application and made it a noteworthy addition to the already expanding range of therapeutic options for MG.
Given the high prevalence of this condition and the scarcity of effective oral therapies already on the market, it is essential to provide a targeted alternative for treatment. In light of this, the clinical study regarding Efgartigimod for the management of gMG constitutes a significant step towards the development of a drug that is globally approved for the treatment of gMG, particularly for those patients who have an anti-AChR antibody that is positive. However, additional research that is both comprehensive and long-term is required before adequate conclusions can be drawn about the efficacy and safety of Efgartigimod.
Ethical approval
None.
Sources of funding
None.
Authors’ contributions
Literature review was done by all authors. O.A.S., R.I., R.M.A., and G.S.: wrote the manuscript. S.O. and K.U.: review editing, formatting, and referencing.
Conflicts of interest disclosure
The authors declare that they have no financial conflict of interest with regard to the content of this report.
Research registration unique identifying number (UIN)
None.
Guarantor
Sidhant Ochani.
References
1. Phillips WD, Vincent A. Pathogenesis of myasthenia gravis: update on disease types, models, and mechanisms. F1000Res 2016;5:1513.
3. Heo YA. Efgartigimod: first approval. Drugs 2022;82:341–8.
4. Howard JF, Bril V, Vu T, et al. Safety, efficacy, and tolerability of efgartigimod in patients with generalized myasthenia gravis (ADAPT): a multicentre, randomised, placebo-controlled, phase 3 trial. Lancet Neurol 2021;20:526–36.
