Vera Bril, MD, FRCPC, lead investigator of the MycarinG study, shared her reactions to recent approval of rozanolixizumab-noli, the first approved therapy for both subtypes of generalized myasthenia gravis in adults.
Rozanolixizumab (Rystiggo; UCB Pharma) is a humanized IgG4 monoclonal antibody that binds to the neonatal Fc receptor, which results in the reduction of circulating IgG. Administered subcutaneously, it carries a warning for increased risk of infections as well as aseptic meningitis and hypersensitivity reactions. Recently, the FDA approved rozanolixizumab-noli as a treatment for adults with generalized myasthenia gravis (gMG) who are either anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive, the most common subtypes of gMG.1
The approval was based on data from the phase 3 MycarinG study (NCT03971422), in which rozanolixizumab-treated patients showed significant reductions in Myasthenia Gravis-Activities of Daily Living (MG-ADL) scores (P <.001) over a 43-day period.In the study, 200 patients were randomly assigned 1:1:1 to either rozanolixizumab 7 mg/kg (n = 66), 10 mg/kg (n = 67) or placebo (n = 67) for 6 weeks, followed by an observation period for 8 weeks. At the conclusion of the trial, the agent continued to show significant impacts on secondary end points as well, including the Quantitative Myasthenia Gravis (QMG) score, a categorical grading system that assessed muscle weakness.2
Following the approval, lead investigator Vera Bril, MD, FRCPC, professor of medicine/neurology, University of Toronto; and director, Neuromuscular Section, division of neurology, University of Toronto sat down in an interview with NeurologyLive® to share her reactions to the news. She talked about her anticipation with the therapy in shifting the landscape of care in MG, specifically noting positive downstream effects of using the treatment in the clinical practice. Bril also spoke about the data that was used to support the approval, including the safety observations clinicians should be aware of.
Vera Bril, MD, FRCPC: Great excitement for the patients.
It is probable that patients will prefer subcutaneous therapy over intravenous infusions for the convenience and [will] likely [experience] fewer adverse-effects, so I expect this medication to be widely used. The subcutaneous approach also spares the veins of patients compared with intravenous therapy.
This is great news for those with MuSK autoantibody-positive MG as well as AChR autoantibody-positive patients with gMG. For the MuSK autoantibody-positive patients specifically, this type of therapy had not yet been approved until now for this population.Rozanolixizumab-noli will be a step forward for this group of patients.
Rozanolixizumab-noli improved activities of daily living measured with MG-ADL, a patient-reported outcome, and also an objective physician scale, the quantitative MG score. Also, multiple additional measures that included patient- and physician-reported outcomes changed positively with rozanolixizumab.
There is an increased risk of headache and infections with this type of therapy that should be kept in mind; however, in clinical trials, rozanolixizumab-noliwas well-tolerated and demonstrated an acceptable safety profile.
Headaches and infections are the major concerns when giving this therapy. The most common infections (at least 5% frequency) were upper respiratory tract infections (17%), COVID-19 (14%), urinary tract infections (9%), and herpes simplex (6%) and no opportunistic infections occurred. Serious infections were reported in 4% of patients treated with rozanolixizumab-noli. Three fatal cases of pneumonia identified were caused by COVID-19 infection in 2 patients and an unknown pathogen in 1 patient. Six cases of infections led to discontinuation of rozanolixizumab-noli. In the MyCarinG study, the majority of the headaches were mild to moderate and 7 (5.3%) cases of severe headache were reported in patients treated with rozanolixizumab-noli. Generally, severe headache was well managed with non-opioid analgesics, and all patients recovered fully with no sequelae; no patients had severe headache recurrence. One (2%) patient in the rozanolixizumab 7 mg/kg group discontinued owing to a severe headache. One (1%) patient in the rozanolixizumab 10 mg/kg group had a severe headache classified as serious, which did not lead to treatment interruption, dose change, or discontinuation.
Treatment with this FcRn inhibitor promises to replace IV and SC immunoglobulin therapies for the treatment of MG.This is of great importance given the vulnerability of the supply of immunoglobulins. Our patients will have a more secure treatment when needed.
Transcript edited for clarity.