Pharmacokinetic (PK) and pharmacodynamic (PD) findings support the use of ravulizumab every 8 weeks for the treatment of adult patients with acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR Ab+ gMG).
This is according to a study by a team of international researchers led by James F. Howard Jr., MD, from the University of North Carolina in Chapel Hill that was published in the Journal of Neurology.
The team analyzed the PKs, PDs, and potential immunogenicity of ravulizumab using data from the placebo-controlled period of the phase 3, double-blind, randomized CHAMPION MG study.
They found that target serum concentrations of ravulizumab of more than 175 µg/mL were achieved within 30 minutes of the completion of the first infusion. They were maintained throughout the 26-week treatment period, and this did not depend on the weight of the patient.
Read more about the treatment of myasthenia gravis
After the last maintenance dose, the mean maximum/peak observed serum concentration of ravulizumab was 1548 µg/mL, and the serum concentration at the end of the dosing interval was 587 µg/mL. Again, there were no significant differences between patients of different body weights.
The inhibition of free serum complement C5 occurred immediately, was complete, and was sustained throughout the treatment period for all patients.
The researchers reported no treatment-emergent antidrug antibodies.
“PK/PD evidence supports the use of ravulizumab every 8 weeks for immediate, complete, and sustained inhibition of terminal complement C5 in adults with AChR Ab+ gMG,” the researchers concluded.
Ravulizumab is a humanized monoclonal antibody that specifically binds to and inhibits the terminal complement C5. The inhibition of C5 prevents the cascade of events that leads to the destruction of the neuromuscular junction and the muscle weakness that occurs as a result. The long half-life of ravulizumab allows for extended periods of time between doses.
References
Vu T, Ortiz S, Katsuno M, et al. Ravulizumab pharmacokinetics and pharmacodynamics in patients with generalized myasthenia gravis. J Neurol. Published online March 9, 2023. doi:10.1007/s00415-023-11617-1
Safety and efficacy study of ravulizumab in adults with generalized myasthenia gravis. ClinicalTrials.gov. April 18, 2019. Updated May 26, 2022. Accessed March 28, 2023.
