FDA Approves Rystiggo (rozanolixizumab-noli) for Generalized Myasthenia Gravis
核心洞察
The FDA has approved Rystiggo (rozanolixizumab-noli) for treating generalized myasthenia gravis (搜索) (gMG) in adults with specific antibody-positive subtypes.
Rystiggo, a humanized IgG4 monoclonal antibody, reduces circulating IgG levels by binding to the neonatal Fc receptor (FcRN (搜索)).
Clinical trials demonstrated statistically significant improvements in MG-ADL and QMG scores with Rystiggo compared to placebo.
The U.S. Food and Drug Administration (FDA) has approved Rystiggo (rozanolixizumab-noli) for the treatment of generalized myasthenia gravis (搜索) (gMG) in adult patients who are anti-acetylcholine receptor (搜索) (AChR) or anti-muscle-specific tyrosine kinase (MuSK (搜索)) antibody positive. This approval marks a significant advancement in the treatment landscape for gMG, a rare autoimmune neuromuscular disease affecting approximately 100 to 350 cases per 1 million people globally. Rystiggo is developed by UCB (搜索), a global biopharmaceutical company.
Mechanism of Action
Rozanolixizumab-noli is a humanized IgG4 monoclonal antibody administered via subcutaneous infusion. It functions by binding to the neonatal Fc receptor (FcRN (搜索)), which results in the reduction of circulating Immunoglobulin G (IgG) antibodies. Pathogenic IgG autoantibodies are a key driver of gMG disease pathology, impairing synaptic transmission at the neuromuscular junction (NMJ). By reducing these autoantibodies, rozanolixizumab-noli helps to improve muscle function and reduce the severity of gMG symptoms.
Clinical Efficacy
The FDA approval was supported by data from the pivotal Phase 3 MycarinG study (NCT03971422), which was published in The Lancet Neurology. The study evaluated the efficacy and safety of rozanolixizumab in adult patients with gMG. The primary efficacy endpoint was the change from baseline in the Myasthenia Gravis (搜索)-Activities of Daily Living Profile (MG-ADL) total score at day 43. The MG-ADL is an eight-item scale assessing the impact of gMG on daily functions, with higher scores indicating greater impairment.
Results showed a statistically significant difference favoring rozanolixizumab-noli, with a -3.4 point change in the MG-ADL total score in the treatment group compared to a -0.8 point change in the placebo group (p<0.001). Secondary endpoints included changes in the Quantitative MG (QMG) score, a 13-item categorical grading system assessing muscle weakness. Rozanolixizumab-noli demonstrated a statistically significant improvement in the QMG total score change from baseline, with -5.4 points and -6.7 points in the ≈7mg/kg and ≈10 mg/kg dose groups, respectively, compared to -1.9 points in the placebo group (p<0.001).
Safety Profile
The most common adverse reactions reported in at least 10% of patients treated with rozanolixizumab-noli were headache, infections, diarrhea, pyrexia, hypersensitivity reactions, and nausea. Serious infections were reported in 4% of patients. The prescribing information includes warnings and precautions regarding infections, immunization, aseptic meningitis, and hypersensitivity reactions.
Patient Perspective
Professor Vera Bril, Professor of Medicine (Neurology) at the University of Toronto and lead investigator of the MycarinG study, noted, "gMG can cause unpredictable fluctuations in severity and frequency of symptoms, which are often debilitating and can substantially impact the lives of patients... There is a significant need for new, innovative treatment options to reduce the day-to-day burden of gMG. Rozanolixizumab-noli is a new treatment option, targeting one of the mechanisms of disease to provide symptom improvement in patient-and physician reported outcomes at day 43."
Availability
Rozanolixizumab-noli will be commercially available in the U.S. during the 3rd quarter of 2023. The FDA reviewed rozanolixizumab-noli under Priority Review. Rozanolixizumab is also currently under review by the European Medicines Agency (EMA) and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) for the treatment of adults with gMG. Responses from regulatory agencies to these submissions are expected by H1 2024.
EU Approves New Administration Methods for Rystiggo
In January 2025, the Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion for the self-administration of RYSTIGGO® (rozanolixizumab) via an infusion (syringe pump) or a new manual push syringe method, after training from a healthcare professional. This approval underscores UCB (搜索)’s commitment to providing people living with generalized myasthenia gravis (搜索), and their caregivers, with treatments that suit their individual needs and preferences. The manual push method allows administration at a flow rate that is comfortable for the patient to accommodate individual preferences. In clinical trials, infusion times by manual push for rozanolixizumab ranged from 1 to 30 minutes with a median infusion time of just 5 minutes per patient.