Rozanolixizumab 420mg/3ml solution for infusion vials

Rozanolixizumab is a humanized high-affinity anti-human neonatal Fc receptor (FcRn) monoclonal antibody (IgG4P) targeting the immunoglobulin G (IgG). Rozonolixizumab itself is an IgG4P, an inactive isotype, to reduce the likelihood of unwanted chain exchange.[A260177] It is investigated for use in autoimmune and alloimmune diseases with pathologic IgG, particularly generalized myasthenia gravis.[A260182] Generalized myasthenia gravis is characterized by the formation of IgG antibodies against the nicotinic acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK).[A260187][A260192][A260197] Approximately 80% of myasthenia gravis patients tested positive for the AChR autoantibodies, and 40% of these AChR-negative or seronegative patients were found to have MuSK autoantibodies.[A260207]

AChR is vital for signal transduction in the neuromuscular junctions (NMJ) by generating muscle end plate potentials to propagate action potential.[A260192] Therefore, the presence of AChR-antibodies can interfere with the ACh-mediated downstream signaling, thus reducing the likelihood of end plate potentials reaching the threshold needed to trigger an action potential.[A260192] As a result, the main clinical manifestation of myasthenia gravis is easily fatigable or persistent muscle weakness.[A260192] On the other hand, MuSK activation can trigger the clustering of AChR at the NMJ, guide the innervation of motor neurons toward AChR-dense areas, and anchor acetylcholinesterase.[A260187][A260202] Therefore, autoantibodies against MuSK can also affect the signal propagation at the NMJ.

Rozanolixizumab-noli is available under the brand name RYSTIGGO and was developed by UCB.[L47122] It was granted orphan drug designation by the FDA in 2019, by the European Medicines Agency (EMA) in April 2020, and by the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) in November 2020.[L47122] In June 2023, Rozanolixizumab-noli was approved by the FDA under Priority Review for the treatment of adult patients with generalized myasthenia gravis who are positive for the anti-acetylcholine receptor (AchR) or anti-muscle-specific tyrosine kinase (MuSK) antibody.[L47122] This is due to the efficacy demonstrated in the pivotal Phase 3 MycarinG study (NCT03971422).[L47122] Rozanolixizumab was also approved by the European Commission on January 5, 2024.[L50973]