The FDA Approves Subcutaneous Infusion of Rystiggo to Treat AChR or MuSK Antibody-Positive Generalized Myasthenia Gravis

The Food and Drug Administration (FDA) has approved Rystiggo (rozanolixizumab-noli, UCB, Atlanta, GA) as a subcutaneous infusion for the treatment of adults with generalized myasthenia gravis (gMG) who are anti-acetycholine receptor (AChR) or anti–muscle-specific tyrosine kinase (MuSK) antibody positive based on findings published in The Lancet Neurology. Rystiggo was under Priority Review with the FDA and was approved based on safety and efficacy data from the pivotal phase 3 MycarinG clinical study (NCT03971422).

MycarinG was a randomized, double-blind, placebo-controlled, adaptive study at 81 outpatient centers and hospitals enrolling 200 patients with MuSK or AChR autoantibody-positive gMG. Participants received Rystiggo 7 mg/kg, Rystiggo 10 mg/kg, or placebo  The primary efficacy endpoint, change in Myasthenia Gravis Activities of Daily Living (MG-ADL) score from baseline to day 43, was met, with greater reductions in MG-ADL scores for Rystiggo-treated participants in the Rystiggo 7 mg/kg group (least-squares mean change -3.37 [SE 0.49]) and in the Rystiggo 10 mg/kg group (-3.40 [0.49]) than with placebo (-0.78 [0.49]; for 7 mg/kg, least-squares mean difference -2.59 [95% CI -4.09 to -1.25], P<0·0001; for 10 mg/kg, -2.62 [-3.99 to -1.16], P<0.0001). Lower scores represented reduced impairment in talking, breathing, swallowing, and rising from a seated-position. The secondary endpoint, change in quantitative myasthenia gravis (QMG) score from baseline to day 43, was also met. Rystiggo-treated participants showed a -5.4 and -6.7 point change in QMG at 7 mg/kg and 10 mg/kg doses, respectively vs -1.9 points in placebo (P<0.001). The most commonly reported adverse reactions were headache, diarrhea, infections, pyrexia, nausea, and hypersensitivity reactions.

“There is a significant need for new, innovative treatment options to reduce the day-to-day burden of gMG,” said Vera Bril, FRCPC, MD, Lead Investigator on the MycarinG study. “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.”

Rystiggo, a humanized IgG4 monoclonal antibody targeting the neonatal Fc receptor (FcRN), is currently the only FDA-approved treatment for the MuSK- or AChR-antibody positive subtypes of gMG. Rystiggo is also under review by the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) and the European Medicines Agency (EMA).