A disease of the neuromuscular junction, Myasthenia Gravis benefits from relatively intense therapeutic research for a rare disease with more than 60 clinical trials underway or in preparation registered on the ClinicalTrials website at the beginning of February 2023.
Among the therapeutic avenues under investigation is the promising family of antibodies directed against neonatal Fc receptors (FcRN): efgartigimod, rozanolixizumab, nipocalimab, batoclimab, ALXN1830… FcRNs increase the recycling of serum albumin, but also of immunoglobulin G (IgG), which includes the autoantibodies detected in nearly 85% of myasthenia patients (most often anti-RACh, anti-MUSK…) and which exert a pathogenic effect. The anti-FcRNs bind to these receptors and thereby promote a reduction in circulating IgG levels.
Effective and well tolerated
Conducted in some 15 countries including France, the randomised, placebo-controlled phase III trial ADAPT evaluated efgartigmod in 167 myasthenia gravis patients, including 6 with anti-MuSK autoantibodies and 32 seronegative (neither anti-RACh nor anti-MuSK). After the announcement of encouraging preliminary results in May 2020, the final results of ADAPT were published in July 2021 and show :
- probable selectivity for efgartigimod, which reduces serum IGg levels but has no effect on albumin or other Ig levels;
- the achievement of the primary endpoint of the trial since 68% of anti-RACh+ patients had a significant (≥ 2 points) and durable (≥ 4 weeks) improvement in MG-ADL score after the first cycle of treatment (one weekly infusion for four weeks), versus 30% in the placebo group; all autoantibody statuses combined, 68% of the participants on efgartigimod were also responders with respect to MG-ADL score at the end of the first cycle of treatment, versus 37% on placebo;
- a return to normal IgG levels by week 12, even though one-third of anti-RACh+ responders on the MG-ADL score continued to show significant clinical improvement;
- side effects reported by 77% of efgartigimod and 84% of placebo patients, and severe in 5% and 8% of cases respectively; the most frequent side effects were mild to moderate in intensity, such as headache (29% for efgartigimod vs. 28% for placebo) and nasopharyngitis (12% vs. 18%).
Efgartigimod (Vyvgart®) was granted marketing authorisation in August 2022, with early access authorisation in combination with standard treatment, in adults with refractory generalized myasthenia gravis autoantibodies. Since then, results from an ancillary study have been released showing significant, early and sustained improvement in quality of life with efgartigimod versus placebo.
