Generalised myasthenia gravis (gMG) is a rare disease with symptoms that include severe muscular weakness and which is characterised by dysfunction and damage at the neuromuscular junction
This weakness can be life-threatening if it affects the muscles required for respiration; it can also cause difficulty in swallowing, chewing and talking, and lead to double vision and drooping eyelids.
In patients with the disease, pathogenic IgG autoantibodies can impair synaptic transmission at the neuromuscular junction through targeting proteins on the post-synaptic membrane.
The result is the disruption of the nervous system’s ability to stimulate the muscle, leading to a weaker contraction. It can occur in anyone, regardless of age, gender or race.
UCB’s rozanolixizumab is a humanised IgG4 monoclonal antibody that binds to the human neonatal Fc receptor (FcRn).
The idea is that by blocking the interaction of FcRn with immunoglobulin G, it will accelerate the catabolism of antibodies and therefore reduce the concentration of pathogenic IgG autoantibodies.1
After a successful Phase I study, in which 49 healthy subjects were given 1, 4 or 7 mg/kg of the antibody or a placebo — leading to dose-dependent reductions in serum IgG levels — a Phase IIa randomised, double-blind, placebo-controlled two-period study was done with 43 gMG patients.2,3
In the first period, encompassing days 1–29, subjects were given three once-weekly subcutaneous infusions of either 7 mg/kg of rozanolixizumab or a placebo.
In the second period, days 29–43, they were randomised again to receive weekly infusions of 4 or 7 mg/kg, followed by an observation period up to day 99. The primary endpoint was the change from baseline to day 29 in the quantitative myasthenia gravis score.
Although this change proved not to be statistically significant, at a mean decline of 1.8 (drug) and 0.7 (placebo), the efficacy measured continued to improve in the second period; overall, the data suggested that it was generally well tolerated and may provide clinical benefit.
In a subsequent randomised, double-blind, placebo-controlled adaptive Phase III study, 200 gMG patients — with either acetylcholine receptor or muscle-specific kinase autoantibody positive gMG — were given weekly subcutaneous infusions for 6 weeks of either 7 or 10 mg/kg of rozanolixizumab or a placebo.4
The primary efficacy endpoint was the change from baseline to day 43 in the myasthenia gravis activities of the daily living profile MG-ADL score, and this was greater in the two active treatment groups (a fall of 3.37 with the 7 mg/kg dose and 3.40 with 10 mg/kg) than with the placebo (a decline of 0.78).
The most common treatment-emergent adverse events were headache, diarrhoea and pyrexia.