Background

Generalized myasthenia gravis is an autoimmune neuromuscular disorder characterized by muscle weakness and fatigue. IgG antibodies occur in up to 85% of patients which are most frequently directed at the acetylcholine receptor (85% of patients) or the anti-muscle-specific tyrosine kinase (MuSK) antibody (6% of patients). Treatment includes the use of cholinesterase inhibitors to prevent the breakdown of acetylcholine at the neuromuscular junction, immunosuppressive therapies, and thymectomy. Myasthenic crisis may occur which is a medical emergency due to respiratory failure and treatment includes plasmapheresis, IVIG, and corticosteroids.

Rozanolixizumab (Rystiggo) is FDA-approved for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive or anti-muscle-specific tyrosine kinase (MuSK) antibody positive. It is a recombinant, humanized immunoglobulin G4 (IgG4) monoclonal antibody that binds to the neonatal Fc receptor (FcRn) and reduces circulating IgG.

Rozanolixizumab was compared to placebo in 200 patients with AChR antibody positive or anti-MuSK antibody positive generalized myasthenia gravis in a 18-week study. The study consisted of a 4-week initial screening period, a 6 week dosing period and an 8 week observation period. The patients were randomized to receive either a weight-based dose of rozanolixizumab as 7 mg/kg or 10 mg/kg or placebo. The patients were included if they had a Myasthenia Gravis Foundation of America (MGFA) clinical classification of class II – IVa and a Myasthenia Gravis Activities of Daily Living (MG-ADL) total score of at least 3 (with at least 3 points from non-ocular symptoms). The patients also had to be on a stable dose of medication that included acetylcholinesterase (AChE) inhibitors, steroids, or non-steroidal immunosuppressive therapies alone or in combination. There were over 83% of patients who received AChE inhibitors, over 56% receiving steroids, and approximately 50% received non-steroidal immunosuppressive therapies. Patients had IgG levels of at least 5.5 g/L, a median time since diagnosis of MG of 6 years, a median MG-ADL total score of 8, and the median Quantitative Myasthenia Gravis (QMG) total score of 15. The MG-ADL was used to evaluate the efficacy of treatment. The MG-ADL quantifies the impact of gMG on 8 signs or symptoms with a score ranging from 0 to 24, with a higher score indicating less ability to perform a function. The primary endpoint was the change in baseline MGADL between groups at day 43. A statistically significant improvement in the percentage of MG - ADL responders was demonstrated with the use of rozanolixizumab as compared to placebo (-3.4 points for each weight based dosing groups vs 0.8 points for placebo, p < 0.001). The QMG was used to assess secondary endpoint of change in baseline to day 43 (range 0 – 39 with higher score indicating severe weakness). The percentage of QMG responders was significantly higher in the patients treated with rozanolixizumab vs the placebo group (-5.4 points for 7 mg/kg group and - 6.7 points for 10 mg/kg group vs - 1.9 points for placebo, p < 0.001). The most common adverse reactions in patients with treated with rozanolixizumab included headache, respiratory tract infections, diarrhea, and pyrexia.

Policy (Criteria)

Initial requests for Rystiggo (rozanolixizumab-noli) may be approved if the following criteria are met:

1. Individual is 18 years of age or older; AND
2. Individual has a diagnosis of generalized myasthenia gravis (gMG); AND
3. Documentation is provided that individual has one of the following:
   1. A positive serologic test for the presence of anti-acetylcholine receptor antibodies (AchR-Ab+); OR
   2. A positive serologic test for the presence of anti-muscle-specific tyrosine kinase (MuSK) antibodies;

AND

4. Individual has Myasthenia Gravis Foundation of America (MGFA) Clinical Classification Class II to Iva disease (Bril 2023); AND
5. Documentation is provided that individual has a Myasthenia Gravis Activities of Daily Living (MG - ADL) score  of at least 3 or higher (Bril 2023); AND
6. Documentation is provided that individual meets both of the following (A and B):
   1. Individual has had a trial and inadequate response or intolerance to an acetylcholinesterase inhibitor; OR
      1. Individual is on a stable dose of an acetylcholinesterase inhibitor; OR
      2. Individual has a contraindication to acetylcholinesterase inhibitors;
   2. Individual has had a trial and inadequate response or intolerance to one or more  immunosuppressive agents (including but not limited to systemic corticosteroids or non steroidal  immunosuppressants); OR
      1. Individual is on a stable dose of one or more immunosuppressive agents (including but not limited to systemic corticosteroids or non-steroidal immunosuppressants); OR
      2. Individual has a contraindication to systemic corticosteroids and non-steroidal immunosuppressants;

Initial Approval Duration: 26 weeks

Requests for continued use of Rystiggo (rozanolixizumab-noli) may be approved if the following criteria are met:

1. Individual has experienced a prior clinical response to rozanolixizumab-noli treatment as defined by the following:
   1. Reduction in signs or symptoms that impact daily function; AND
   2. Documentation is provided of at least a 2 - point reduction in MG - ADL total score from pre-treatment  baseline;

AND

1. Individual requires continued treatment to maintain response or to regain clinically meaningful response.

Requests for Rystiggo (rozanolixizumab-noli) may not be approved for the following:

1. Individual is using in combination with maintenance immunoglobulin treatment, eculizumab, ravulizumab,  efgartigimod-alfa, zilucoplan, or rituximab; OR
2. If the above criteria are not met and for all other indications.

Continuation Approval Duration: 1 year

References

1. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc. Accessed Jul 26, 2023.
2. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Accessed Jul 26, 2023.
3. National Organization of Rare Diseases. https://rarediseases.org/rare-diseases. 4.
4. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2023 [cited Jul 26, 2023]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/. 5.
5. Rystiggo (rozanolixizumab-noli) injection. UCB, Inc. Smyrna, GA. June 2023.

Coding Section

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each Policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

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