DRUG INFORMATION
Rozanolixizumab-noli (Rystiggo) is a neonatal Fc receptor blocker indicated for the treatment of generalized myasthenia gravis (gMG) in adult individuals who are anti-acetylcholine receptor (AChR) or antimuscle-specific tyrosine kinase (MuSK) antibody positive.
GENERALIZED MYASTHENIA GRAVIS
Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disease that causes weakness in the skeletal muscles. The muscle weakness usually worsens after periods of activity and improves after periods of rest. Muscles that control movements of the eye and eyelid, facial expression, chewing, talking, and swallowing are often involved, but those that control breathing and neck and limb movements may also be involved. This weakness is a result of an antibody-mediated, T-cell dependent, immunological attack directed at proteins in the postsynaptic membrane of the neuromuscular junction. MG has an annual incidence of about seven to 23 cases per million. It most often begins before the age of 40 in women and after age 60 in men.
PEER-REVIEWED LITERATURE
SUMMARY
The efficacy of rozanolixizumab-noli (Rystiggo) for the treatment of generalized MG was demonstrated in the MycarinG trial, a randomised, double-blind, placebo-controlled, adaptive phase 3 study. Enrolled individuals were 18 years or older with acetylcholine receptor (AChR) or muscle-specific kinase (MuSK) autoantibody-positive gMG (Myasthenia Gravis Foundation of America class II–IVa), a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of at least 3 (nonocular symptoms), and a quantitative myasthenia gravis score of at least 11. Individuals were randomly assigned (1:1:1) to receive subcutaneous infusions once a week for 6 weeks of either rozanolixizumab-noli (Rystiggo) 7 mg/kg, rozanolixizumab-noli (Rystiggo) 10 mg/kg, or placebo. Randomization was stratified by AChR and MuSK autoantibody status. The primary efficacy endpoint was change from baseline to day 43 in MG-ADL score, assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT03971422) and EudraCT (2019-000968-18); an open-label extension study has been completed (NCT04124965; EudraCT 2019-000969-21) and another is underway (NCT04650854; EudraCT 2020- 003230-20.
Of 200 enrolled individuals, 66 (33%) were randomly assigned to rozanolixizumab-noli (Rystiggo) 7 mg/kg, 67 (34%) to rozanolixizumab (Rystiggo) 10 mg/kg, and 67 (34%) to placebo. Reductions in MG-ADL score from baseline to day 43 were greater in the rozanolixizumab (Rystiggo) 7 mg/kg group (least-squares mean change –3.37 [standard error (SE) 0.49]) and in the rozanolixizumab (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). Adverse events (AE) were experienced by 52 (81%) of 64 individuals treated with rozanolixizumab (Rystiggo) 7 mg/kg, 57 (83%) of 69 treated with rozanolixizumab (Rystiggo) 10 mg/kg, and 45 (67%) of 67 treated with placebo. The most frequent AEs were headache (29 [45%] individuals in the rozanolixizumab (Rystiggo) 7 mg/kg group, 26 [38%] in the rozanolixizumab (Rystiggo) 10 mg/kg group, and 13 [19%] in the placebo group), diarrhea (16 [25%], 11 [16%], and nine [13%]), and pyrexia (eight [13%], 14 [20%], and one [1%]).
OFF-LABEL INDICATIONS
There may be additional indications contained in the policy section of this document due to evaluation of criteria highlighted in the company's off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.
