Abdeg technology for the treatment of myasthenia gravis: efgartigimod drug experience

ABSTRACT

Introduction

Myasthenia gravis is characterized by fluctuating muscle weakness that improves with rest and worsens with effort or throughout the day.

Areas Covered

Efgartigimod is a human IgG1–derived Fc fragment modified at five residues to increase its affinity for the neonatal Fc receptor by Abdeg technology. Thus, efgartigimod binds to the neonatal Fc receptor and decreases the levels of IgG, including autoantibodies of this isotype. For acetylcholine receptor (AChR) antibody-positive patients, efgartigimod had a higher proportion of MG-ADL responders than placebo in the first treatment cycle. The mean changes of multiple outcomes from baseline were better for efgartigimod than placebo from weeks 1 to 7 in the first treatment cycle. The decrease of IgG and AChR autoantibodies was 61.3% and 57.6% one week after the first treatment cycle ends, respectively. The most common adverse events were headache, nasopharyngitis, nausea, and diarrhea, which occurred in the same proportion in the efgartigimod and placebo groups. Urinary and upper respiratory tract infections were twice as frequent in efgartigimod-treated patients.

Expert Opinion

Efgartigimod was efficacious and safe for generalized myasthenia patients with AChR antibody-positive patients. These findings need to be confirmed in AChR antibody-negative patients, and long-term safety studies are currently ongoing.

Plain Language Summary

Myasthenia gravis patients have a high level of autoantibodies, which can cause fluctuating muscle weakness. In this regard, efgartigimod is a new drug approved to treat myasthenia gravis that decreases antibody levels and symptom improvement. Furthermore, this drug was safe for these patients.

KEYWORDS:

• Efgartigimod
• generalized myasthenia gravis
• neonatal Fc receptor antagonist
• review
• treatment

Article highlights

• Efgartigimod is a human IgG1-derived Fc fragment mutated at 5 residues, resulting in the Abdeg form.

• It is the first neonatal Fc receptor antagonist approved for the treatment of generalized myasthenia gravis in adults who are AChR antibody-positive.

• Its approval occurred on 17 December 2021 by the United States Food and Drug Administration as an orphan drug. In January 2022, efgartigimod received its second regulatory approval in Japan.

• Efgartigimod decreased levels of IgG and AChR autoantibodies.

• These findings need to be confirmed in AChR antibody-negative patients.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One peer reviewer declares serving on advisory boards for UCB, Cabelleta Bio, Roche (all of which are developing drugs for myasthenia gravis); and benefitting from unrestricted donations from Argenx to the MGNet, which is part of the NIH sponsored rare disease network. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Argenx provided a scientific accuracy review at the request of the journal editor.

Author contributions

J dos Santos: conceptualization, methodology, writing - original draft preparation. R Gomes: conceptualization, methodology, writing - original draft preparation. M da Silva: conceptualization, methodology, writing - reviewing and editing. All authors approved the final version of the manuscript to be published.

Additional information

Funding

This paper was not funded.