Kim Moran, Ph.D., MBA, Head of US Rare Diseases at UCB, discusses the two orphan drugs, rozanolixizumab and zilucoplan, which the company hopes to have approved soon to treat myasthenia gravis.
Myasthenia gravis is a rare autoimmune disorder that targets the acetylcholine receptors (AChRs) in the muscle cells.
The hallmark symptom of MG is muscle weakness. It commonly affects the voluntary muscles, particularly those controlling eyes and eyelids, facial expression, chewing, swallowing, and limb movements. As the disease progresses, weakness may extend to other muscles, including those involved in breathing, causing respiratory difficulties.
Treatment may include pyridostigmine, to increase acetylcholine availability at the neuromuscular junction. Immunomodulatory therapies such as corticosteroids, immunosuppressants, and monoclonal antibodies targeting B cells, are also used.
More targeted therapies with fewer side effects are needed for this patient population. As Dr. Moran notes, two orphan drugs developed by UCB that are currently under review by the FDA are rozanolixizumab and zilucoplan.
Rozanolixizumab is a subcutaneous monoclonal antibody that targets the neonatal Fc receptor (FcRn) to treat adults with generalized myasthenia gravis who are anti-AChR or anti-muscle-specific tyrosine kinase (MuSK) antibody positive. A decision by the FDA is expected in the second quarter of 2023. In the Phase 3 MycarinG study, rozanolixizumab significantly improved the Myasthenia Gravis-Activities of Daily Living (MG-ADL) scores by -3.37 in the 7mg/kg cohort (n=66) and -3.40 for the 10mg/kg cohort. (n=67). MG-ADL scores were reduced by -0.78 in the placebo cohort (n=67). This data was recently published in Lancet Neurology.
Zilucoplan is a subcutaneous, self-administered macrocyclic peptide complement C5 inhibitor in development to treat ACHR-positive myasthenia gravis. A decision by the FDA is expected in the latter half of 2023. In the Phase 3 RAISE study, zilucoplan (0.3 mg/kg once daily, subcutaneously) significantly improved the MG-ADL scores by -4.39 in (n=86) compare to -2.30 for the placebo cohort (n=88). This data was also recently published in Lancet Neurology.
As Dr. Silverthorn explains, having two additional treatment options for myasthenia gravis, each with unique mechanisms of action and unique delivery patterns, is necessary due to the complexity and diversity of this patient population.
