The FDA approved rozanolixizumab-noli (Rystiggo), a neonatal Fc receptor blocker, to treat adults with generalized myasthenia gravis (gMG), UCB announced Tuesday.
The drug is the first approved to treat both of the two most common subtypes of gMG patients -- those who are anti-acetylcholine receptor (AChR)-positive and those who are anti-muscle-specific tyrosine kinase (MuSK) antibody-positive.
"gMG can cause unpredictable fluctuations in severity and frequency of symptoms, which are often debilitating and can substantially impact the lives of patients," said Vera Bril, MD, of the University of Toronto, in a UCB press release. "People living with gMG often face treatment options that are broad-acting and that have traditionally only offered symptomatic relief."
A rare autoimmune neuromuscular disease, gMG is characterized by fluctuating muscle weakness and fatigue. Muscle weakness in patients with MuSK autoantibody-positive gMG can be especially severe.
Several factors are thought to drive gMG disease pathology, including complement cascade, immune cells, and pathogenic immunoglobulin G (IgG) autoantibodies. Pathogenic IgG autoantibodies can impair synaptic transmission at the neuromuscular joint by targeting specific proteins on the post-synaptic membrane.
Rozanolixizumab is a subcutaneously administered humanized monoclonal antibody that specifically binds to neonatal Fc receptor. It is designed to block the interaction between neonatal Fc receptor and IgG, causing a reduction in circulating IgG.
The FDA's decision was based on the phase III MycarinG study, which showed that rozanolixizumab led to clinically meaningful improvements in Myasthenia Gravis Activities of Daily Living (MG-ADL) scores and other disease-related endpoints in 200 gMG patients. Results were seen for both the 7-mg/kg and 10-mg/kg doses.
On the primary endpoint of MG-ADL score changes from baseline to day 43, a difference favoring rozanolixizumab was seen (-3.4 points in rozanolixizumab group at either dose vs -0.8 points for placebo, P<0.001). MG-ADL scores assess eight aspects of daily function; total scores can range from 0 to 24 points.
Secondary endpoints included changes from baseline in Quantitative Myasthenia Gravis (QMG) total scores, which can range from 0 to 39 points. At day 43, the QMG score change from baseline was -5.4 points and -6.7 points in the rozanolixizumab 7-mg/kg and 10-mg/kg groups, respectively, compared with -1.9 points for placebo (P<0.001).
The most common adverse reactions reported in at least 10% of rozanolixizumab-treated patients were headache, infections, diarrhea, pyrexia, hypersensitivity reactions, and nausea. Serious infections emerged in 4% of patients. Three fatal cases of pneumonia were identified, two related to COVID-19 and one with an unknown pathogen. Six cases of infections led to treatment discontinuation. Full warnings and precautions are listed on the drug's label.
Rozanolixizumab will be commercially available in the U.S. in the third quarter of 2023, UCB said. The drug currently is under review by the European Medicines Agency and the Japanese Pharmaceuticals and Medical Devices Agency to treat gMG.