U.S. Food and Drug Administration (FDA)-Approved Indications

Rozanolixizumab-noli is available as the brand Rystiggo (UCB, Inc.). Rozanolixizumab-noli is a humanized IgG4 monoclonal antibody that binds to the neonatal Fc receptor (FcRn), resulting in the reduction of circulating IgG.

Rystiggo carries labeled warnings and precautions for infections, aseptic meningitis, and hypersensitivity reactions. Rystiggo may increase the risk for infection. Immunization with vaccines during Rystiggo treatment has not been studied. Serious adverse reactions of aseptic meningitis (also called drug-induced aseptic meningitis) have been reported in patients treated with Rystiggo. Hypersensitivity reactions, including angioedema and rash, were observed in patients treated with Rystiggo.

The most common adverse reactions (10% or more) in patients with generalized myasthenia gravis (gMG) are headache, infections, diarrhea, pyrexia, hypersensitivity reactions, and nausea.

Generalized Myasthenia Gravis (gMG)

Myasthenia gravis is a chronic autoimmune, neuromuscular disease that is characterized by weakness and fatigue of skeletal (voluntary) muscles that worsens after periods of activity and improves after periods of rest. The voluntary muscles affected can include those that are responsible for controlling the eyes, face, mouth, throat, limbs and respiratory muscles. In some affected individuals, the condition may be limited to certain eye muscles, which is often described as “ocular myasthenia". When myasthenia gravis affects multiple muscle groups throughout the body, it is called generalized myasthenia gravis (gMG).

In myasthenia gravis, the immune system produces anti-acetylcholine receptor (AChR) antibodies that interfere with communication between nerves and muscles, resulting in muscle weakness and fatigue. Severe attacks of weakness, such as in myasthenia gravis crisis, can cause breathing and swallowing problems that can be life-threatening.

Myasthenia gravis is chronic but treatable disease, with many individuals achieving remission of symptoms. Initial symptomatic therapy consists of an acetylcholinesterase inhibitor such as oral pyridostigmine. Glucocorticoids and/or other immunosuppressive therapies are indicated for patients who remain significantly symptomatic on pyridostigmine (Bird, 2023).

In June 2023, the FDA approved Rystiggo for the treatment of gMG in adult patients who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive. FDA approval was based on the pivotal Phase 3 MycarinG study that demonstrated that treatment with rozanolixizumab-noli resulted in statistically significant improvements in gMG-specific outcomes, including everyday activities such as breathing, talking, swallowing, and being able to rise from a chair (UCB, 2023b).

Bril et al (2023) conducted a randomized, double-blind, placebo-controlled, multicenter, adaptive phase 3 (MycarinG) study to evaluate the safety and efficacy of rozanolixizumab in patients with AChR or MuSK autoantibody-positive gMG. Selection criteria included patients (aged 18 years or older) with AChR or 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 (non-ocular symptoms), and a quantitative myasthenia gravis (QMG) score of at least 11. Patients were required to be on a stable dose of myasthenia gravis (MG) therapy prior to screening that included acetylcholinesterase (AChE) inhibitors, steroids, or non-steroidal immunosuppressive therapies (NSISTs), either in combination or alone. A total of 200 adult patients were then randomized 1:1:1 to receive weight-tiered doses of rozanolixizumab 7 mg/kg (n=66; 33%), rozanolixizumab 10 mg/kg (n=67; 34%), or placebo (n=67; 34%). The study included a 4-week screening period and a 6-week treatment period followed by 8 weeks of observation. During the treatment period, rozanolixizumab or placebo were administered by subcutaneous infusion once a week for 6 weeks. The efficacy was measured using the MG-ADL scale, which assesses the impact of gMG on daily functions of 8 signs or symptoms that are typically affected in gMG. The primary efficacy endpoint was change from baseline to day 43 in MG-ADL score, assessed in the intention-to-treat population. The secondary endpoint was the change between treatment groups from baseline to day 43 in the QMG score. The QMG is a 13-item categorical grading system that assesses muscle weakness. Treatment-emergent adverse events (TEAEs) were assessed in all randomly assigned patients who received at least one dose of study drug. The authors observed a statistically significant difference favoring rozanolixizumab in the MG-ADL total score change from baseline [-3.4 points in rozanolixizumab-treated group at either dose vs -0.8 points in the placebo-treated group (p<0.001)]. Furthermore, a statistically significant difference favoring rozanolixizumab was observed in the QMG total score change from baseline [-5.4 points and -6.7 points in rozanolixizumab-treated group at ≈7 mg/kg and ≈10 mg/kg dose level, respectively, vs -1.9 points in the placebo-treated group (p<0.001)]. TEAEs were experienced by 52 (81%) of 64 patients treated with rozanolixizumab 7 mg/kg, 57 (83%) of 69 treated with rozanolixizumab 10 mg/kg, and 45 (67%) of 67 treated with placebo. The most frequent TEAEs were headache (29 [45%] patients in the rozanolixizumab 7 mg/kg group, 26 [38%] in the rozanolixizumab 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%]). Five (8%) patients in the rozanolixizumab 7 mg/kg group, seven (10%) in the rozanolixizumab 10 mg/kg group, and six (9%) in the placebo group had a serious TEAE. No deaths occurred. The authors' interpretation of the results were that rozanolixizumab showed clinically meaningful improvements in patient-reported and investigator-assessed outcomes in patients with gMG, for both 7 mg/kg and 10 mg/kg doses. Both doses were generally well tolerated, and that these findings support the mechanism of action of neonatal Fc receptor inhibition in this patient population. The authors concluded that rozanolixizumab represents a potential additional treatment option for patients with gMG.

Appendix

Myasthenia Gravis Foundation of America (MGFA) Clinical Classification

Class I: Any ocular muscle weakness; may have weakness of eye closure. All other muscle strength is normal.

Class II: Mild weakness affecting muscles other than ocular muscles; may also have ocular muscle weakness of any severity.

Class III: Moderate weakness affecting muscles other than ocular muscles; may also have ocular muscle weakness of any severity.

Class IV: Severe weakness affecting muscles other than ocular muscles; may also have ocular muscle weakness of any severity.

Class V: Defined as intubation, with or without mechanical ventilation, except when employed during routine postoperative management. The use of a feeding tube without intubation places the patient in class IVb.

Source: Myasthenia Gravis Foundation of America (MGFA)

: Requires Precertification:

Precertification of rozanolixizumab-noli (Rystiggo) is required of all Aetna participating providers and members in applicable plan designs. For precertification of rozanolixizumab-noli (Rystiggo),

For Medicare Part B plans, call (866) 503-0857, or fax (844) 268-7263.

Criteria for Initial Approval

Aetna considers rozanolixizumab-noli (Rystiggo) medically necessary for treatment of generalized myasthenia gravis (gMG) when

of the following criteria are met:

Aetna considers all other indications as experimental and investigational.

Continuation of Therapy

Aetna considers continuation of rozanolixizumab-noli (Rystiggo) therapy medically necessary for members requesting reauthorization when there is no evidence of unacceptable toxicity or disease progression while on the current regimen and member demonstrates a positive response to therapy (e.g., improvement in MG-ADL score, changes compared to baseline in Quantitative Myasthenia Gravis (QMG) total score).