In a phase 3 study, rozanolixizumab demonstrated statistically significant differences vs placebo on primary and secondary outcomes over a 43-day treatment period.
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The FDA has approved UCB’s investigational agent 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. Marketed as Rystiggo, it becomes the first FDA-approved therapy to treat both subtypes of the disease.1
The basis for the approval was 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. All told, rozanolixizumab 7-mg/kg and 10-mg/kg groups had a least-square mean change on MG-ADL of –3.370 (difference vs placebo, –2.586; 95% CI, –4.091 to –1.249) and –3.403 (difference vs placebo, –2.619; 95% CI, –3.994 to –1.163) compared with –0.784 for those on placebo.2
"gMG can cause unpredictable fluctuations in severity and frequency of symptoms, which are often debilitating and can substantially impact the lives of patients. People living with gMG often face treatment options that are broad-acting, and that have traditionally only offered symptomatic relief,” lead investigator Vera Bril, MD, FRCPC, professor of medicine/neurology, University of Toronto; and director, Neuromuscular Section, division of neurology, University of Toronto, said in a statement.1
"There is a significant need for new, innovative treatment options to reduce the day-to-day burden of gMG. Rystiggo 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," she added.
Administered subcutaneously, rozanolixizumab is a humanized IgG4 monoclonal antibody that binds to the neonatal Fc receptor, resulting in the reduction of circulating IgG. It carries a warning for increased risk of infections, as well as aseptic meningitis, and hypersensitivity reactions. The therapy received orphan drug designation by the European Commission and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) in 2020 and remains currently under review by both agencies.
In MycarinG, 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. At day 43, investigators observed a statistically significant difference on QMG total score favoring rozanolixizumab on QMG total, with point changes of –5.4 and –6.7 in the 7 and 10 mg/kg groups, respectively, vs changes of –1.9 points in the placebo-treated group (P <.001).
Treatment response, considered improvement of at least 2 points on MG-ADL, and 3-point improvement on both QMG and Myasthenia Gravis Composite (MGC) scores, also favored rozanolixizumab. A post-hoc finding from MycarinG, presented at the 2022 American Association of Neuromuscular and Electrodiagnostic Medicine annual meeting, showed that rozanolixizumab-treated patients achieved a better response on all outcomes relative to placebo MG-ADL, 71.9% and 69.4% in 7 mg/kg and 10 mg/kg groups; placebo, 31.3%).3
The QMG scores showed an achieved response in the rozanolixizumab 7-mg/kg, 10-mg/kg, and placebo groups (54.7%, 72.6%, and 39.1%). Similarly, the same respective groups achieved response on MGC (60.9%, 74.2%, and 40.6%). Only 3.0% in the placebo group had minimal symptom expression in comparison with the 7-mg/kg and 10-mg/kg active treatment groups, respectively (25.8% and 28.4%).
In terms of safety, a higher proportion of treatment emergent adverse events (TEAEs) occurred in comparison with placebo (81.3% for 7 mg/kg, 82.6% for 10 mg/kg, and 67.2% for placebo). Reports of the most common TEAEs were headache, diarrhea, pyrexia, and nausea; although, a higher incidence of headache was observed in the rozanolixizumab groups vs placebo.
"No two people living with gMG experience the disease in the same way, so we can't take a 'one size fits all' approach to disease management,” Iris Loew-Friedrich, executive vice president and chief medical officer at UCB, said in a statement. "Disease management should be based on the clinical needs and preferences of the individual patient, and the aim of treatment is to help restore that patient's ability to carry out activities of daily living. The approval of RYSTIGGO® means doctors have an additional approved treatment option for their gMG patients who have not yet found a treatment that meets their needs."1