The neonatal Fc receptor (or FcRn) protects against degradation of immunoglobulins G, which include the auto-antibodies produced in myasthenia gravis (anti-RACh, anti-MuSK, etc.) and which target the neuromuscular junction. A promising therapeutic avenue in this pathology consists in blocking FcRn, so as to reduce the levels of circulating autoantibodies. Several anti-FcRn are being tested, such as rozanolixizumab (or UCB7665).
Sufficient results to enter the phase III
The European health authorities have assigned it the status of orphan drug in immune thrombocytopenia, then in myasthenia gravis where a phase IIa trial (NCT03052751) randomized double-blind against placebo had started in mid-2017. The 43 participants of the study were over 18 years of age with moderate to severe generalized myasthenia gravis, only one with anti-MuSK autoantibodies, the others with anti-RACh. The journal Neurology published the final results of this phase II trial in November 2020. They show for the group taking rozanolixizumab:
- an improvement in the quantitative QMG score on D29 (primary endpoint of the trial) but not statistically significant;
- a significant improvement in MGADL (-1.8 vs -0.4) and composite MG (-3.1 vs -1.2) scores, secondary endpoints;
- a decrease in the level of anti-RACh autoantibodies to -68%, the evolution of anti-MuSKs has not been evaluated (only one participant concerned);
- good overall tolerance of the drug candidate, with headache being the most common side effect, occurring in 57% of participants taking 7mg / kg rozanolixizumab, versus 14% of participants in the placebo group.
- A phase III trial (NCT03971422 or MycarinGstudy) conducted among 240 participants in 15 countries including France started in June 2019, followed four months later by the start of its extension (NCT04124965).
