A disorder affecting the neuromuscular junction, Efgartigimod reaches phase III in myasthenia gravis has benefited from relatively intensive therapeutic research for a rare disease, with more than 50 clinical trials in progress or in preparation registered on the ClinicalTrials site as of the end of July 2021.
The therapeutic avenues studied include the promising class of antibodies targeting neonatal Fc receptors (FcRN): efgartigimod, rozanolixizumab, nipocalimab, batoclimab, ALXN1830, etc. FcRN increase the recycling of serum albumin, but also immunoglobulin G (IgG) which includes auto-antibodies detected in nearly 85% of patients with myasthenia (usually anti-AChR, anti-MUSK, etc.) and which exert a pathogenic effect. Anti-FcRN antibodies bind to these receptors promoting the reduction in circulating IgG levels.
Effective and well tolerated in this trial
Conducted in approximately fifteen countries, including France, the randomised, placebo-controlled phase III “ADAPT” trial has evaluated efgartigmod in 167 patients with myasthenia, including 6 with anti-MuSK auto-antibodies and 32 seronegative patients (no anti-AChR or anti-MuSK). Following the announcement of promising preliminary results in May 2020, the final results of ADAPT were published in July 2021 and demonstrate:
- probable selectivity of efgartigimod, which leads to a reduction in serum IgG levels, but no effect on albumin or other Ig levels;
- achievement of the primary endpoint of the trial since 68% of anti-AChR+ patients show a significant (≥ 2 points) and persistent (≥ 4 weeks) improvement in the MG-ADL score after the first treatment cycle (weekly infusion over four weeks), vs. 30% in the placebo group; all auto-antibody statuses combined, 68% of participants receiving efgartigimod also showed a response in terms of the MG-ADL score at the end of the first treatment cycle, vs. 37% for placebo;
- normalisation of IgG levels in week 12 even though a third of anti-AChR+ participants having shown a response in terms of the MG-ADL score continue to experience significant clinical improvement;
- adverse reactions reported by 77% of participants receiving efgartigimod and 84% for placebo, and serious adverse reactions in 5% and 8% of cases, respectively; the most common are mild to moderate in intensity, such as headache (29% for efgartigimod vs. 28% for placebo) and rhinopharyngitis (12% vs. 18%).
A long-term (three-year) evaluation of the candidate medicinal product is currently in progress as part of the open-label ADAPT+ extension, which is expected to end in June 2023.
