Commercial

Medical Policy

Title:

Rozanolixizumab-noli (Rystiggo)

Policy #:

08.02.08a

Policy

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.

MEDICALLY NECESSARY

ROZANOLIXIZUMAB-NOLI (RYSTIGGO)

Rozanolixizumab-noli (Rystiggo) is considered medically necessary and, therefore, covered for the treatment of adult individuals 18 years of age or older with generalized myasthenia gravis (gMG), when all of the following criteria are met, including dosing and frequency:

Initial Criteria

The individual has documented diagnosis of gMG based individual's history and supported by previous evaluations
The individual has a confirmed positive record of autoantibodies against acetylcholine receptor (AChR) or muscle-specific kinase (MuSK)
The individual has Myasthenia Gravis Foundation of America (MGFA) Class II, III, IVa
The individual has Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of at least 3 (with ≥3 points from non-ocular symptom) AND a quantitative myasthenia gravis (QMG) score of at least 11
The individual has a history of inadequate response or intolerance one of the following:

standard-of-care therapy (i.e, acetylcholinesterase inhibitors [AChEIs], e.g., pyridostigmine or corticosteroids, e.g., prednisone)
use of immunoglobulin G (IVIG)/plasma exchange (PLEX) as rescue therapy

The individual is not receiving rozanolixizumab-noli (Rystiggo) in combination with eculizumab (Soliris), ravulizumab (Ultomiris) or efgartigimod alfa-fcab (Vyvgart)
Dosing and frequency for rozanolixizumab-noli (Rystiggo) is based on a body weight (BW) of the individual, once weekly for six weeks with every next cycle initiated not sooner than 63 days from the start of the previous treatment cycle:

if BW less than 50 kg: 420 mg
if BW 50 kg to less than 100 kg 560 mg
if BW 100 kg and above 840 mg

Continuation Criteria

Submission of medical records to demonstrate a positive clinical response from baseline (e.g., two-point reduction in MG-ADL total score). The safety of initiating subsequent cycles sooner than 63 days from the start of the previous treatment cycle has not been established.

EXPERIMENTAL/INVESTIGATIONAL

All other uses for rozanolixizumab-noli (Rystiggo) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

DOSING AND FREQUENCY REQUIREMENTS

The Company reserves the right to modify the Dosing and Frequency Requirements listed in this policy to ensure consistency with the most recently published recommendations for the use of rozanolixizumab-noli (Rystiggo). Changes to these guidelines are based on a consensus of information obtained from resources such as, but not limited to: the US Food and Drug Administration (FDA); Company-recognized authoritative pharmacology compendia; or published peer-reviewed clinical research. The professional provider must supply supporting documentation (i.e., published peer-reviewed literature) in order to request coverage for an amount of rozanolixizumab-noli (Rystiggo) outside of the Dosing and Frequency Requirements listed in this policy. For a list of Company-recognized pharmacology compendia, view our policy on off-label coverage for prescription drugs and biologics.

Accurate member information is necessary for the Company to approve the requested dose and frequency of this drug. If the member’s dose, frequency, or regimen changes (based on factors such as changes in member weight or incomplete therapeutic response), the provider must submit those changes to the Company for a new approval based on those changes as part of the utilization management activities. The Company reserves the right to conduct postpayment review and audit procedures for any claims submitted for rozanolixizumab-noli (Rystiggo).

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

When coverage of rozanolixizumab-noli (Rystiggo) is requested outside of the Dosing and Frequency Requirements listed in this policy, the prescribing professional provider must supply documentation (i.e., published peer-reviewed literature) to the Company that supports this request.

Guidelines

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, rozanolixizumab-noli (Rystiggo) is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

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.

A. IIa. Predominantly affecting limb, axial muscles, or both. May also have lesser involvement of oropharyngeal muscles.
B. IIb. Predominantly affecting oropharyngeal, respiratory muscles, or both. May also have lesser or equal involvement of limb, axial muscles, or both.

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

A. IIIa. Predominantly affecting limb, axial muscles, or both. May also have lesser involvement of oropharyngeal muscles.
B. IIIb. Predominantly affecting oropharyngeal, respiratory muscles, or both. May also have lesser or equal involvement of limb, axial muscles, or both.

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

A. IVa. Predominantly affecting limb, axial muscles, or both. May also have lesser involvement of oropharyngeal muscles.
B. IVb. Predominantly affecting oropharyngeal, respiratory muscles, or both. May also have lesser or equal involvement of limb, axial muscles, or both.

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 individual in class IVb.

MG Activities of Daily Living (MG-ADL) Profile

Grade	Score
Activities of Daily Living (ADL)	0	1	2	3
Talking	Normal	Intermittent slurring or nasal speech	Constant slurring or nasal, but can be understood	Difficult to understand speech
Chewing	Normal	Fatigue with solid food	Fatigue with soft food	Gastric tube
Swallowing	Normal	Rare episode of choking	Frequent choking necessitating changes in diet	Gastric tube
Breathing	Normal	Shortness of breath with exertion	Shortness of breath at rest	Ventilator dependence
Impairment of ability to brush teeth or comb hair	None	Extra effort, but no rest periods needed.	Rest periods needed	Cannot do one of these functions
Impairment of ability to arise from a chair	None	Mild, sometimes uses arms	Moderate, always uses arms	Severe, requires assistance
Double vision	None	Occurs, but not daily	Daily, but not constant	Constant
Eyelid droop	None	Occurs, but not daily	Daily, but not constant	Constant

Quantitative Myasthenia Gravis

The QMG is a 13-item direct physician assessment scoring system that quantifies disease severity based on impairments of body functions and structures. Each item is quantitatively assessed and scored from 0 to 3 (where 3 represents the most severe), providing a total QMG score ranging from 0 to 39. The QMG is composed of the following items: ocular (two items), facial (one item), bulbar (two items), gross motor (six items), axial (one item), and respiratory (one item). According to a 2000 publication by the Task Force of the Medical Scientific Advisory Board of the MGFA, the QMG score was recommended for use in all prospective MG clinical trials for evaluating treatment-related clinical change.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Rozanolixizumab-noli (Rystiggo) was approved by the FDA on June 27, 2023, for the treatment of generalized myasthenia gravis (gMG) in adult individuals who are anti-acetylcholine receptor (AchR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive.

PEDIATRIC USE

The safety and effectiveness have not been established in the pediatric population for rozanolixizumab-noli (Rystiggo).

Description

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 (non-ocular 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 changed 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-noli (Rystiggo) 10 mg/kg, and 67 (34%) to placebo. Reductions in MG-ADL score from baseline to day 43 were greater in the rozanolixizumab-noli (Rystiggo) 7 mg/kg group (least-squares mean change –3.37 [SE 0.49]) and in the rozanolixizumab-noli (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-noli (Rystiggo) 7 mg/kg, 57 (83%) of 69 treated with rozanolixizumab-noli (Rystiggo) 10 mg/kg, and 45 (67%) of 67 treated with placebo. The most frequent AEs were headache (29 [45%] individuals in the rozanolixizumab-noli (Rystiggo) 7 mg/kg group, 26 [38%] in the rozanolixizumab-noli (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.

References

American Academy of Neurology(AAN). Myasthenia gravis activities of daily living profile. [ANN Web site]. 04/01/1999.

Bril V, Drużdż A, Grosskreutz J, et al. Safety and efficacy of rozanolixizumab in patients with generalised myasthenia gravis (MycarinG): a randomised, double-blind, placebo-controlled, adaptive phase 3 study. Neurology. 2023;22:383-394.

Centers for Medicare & Medicaid Services (CMS). Guidance for Prior Authorization and Step Therapy for Part B Drugs in Medicare Advantage. 08/07/2018. Available at: https://www.cms.gov/Medicare/Health-Plans/HealthPlansGenInfo/Downloads/MA_Step_Therapy_HPMS_Memo_8_7_2018.pdf.

Elsevier’s Clinical Pharmacology Compendium.Rozanolixizumab-noli (Rtiggo). [Clinical Key Web site]. 07/05/23. Available at: https://www.clinicalkey.com/pharmacology/monograph/3533?n=Soliris [via subscription only]. Accessed August 4, 2023.

ClinicalTrials.gov. A Study to Test Efficacy and Safety of Rozanolixizumab in Adult Patients With Generalized Myasthenia Gravis. ClinicalTrials.gov Identifier: NCT03971422. First Posted: June 3, 2023; Last Update Posted: May 6, 2023 Available at: Study Record | ClinicalTrials.gov. Accessed August 4, 2023.

Lexi-Drugs Compendium. Rozanolixizumab-noli (Rtiggo). [Lexicomp Online Web site]. 06/27/2023. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed August 4, 2023.

Truven Health Analytics Inc. Micromedex® 2.0 Healthcare Series. DrugDex®. Rozanolixizumab-noli. [Micromedex Web site]. 07/18/23. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed August 4, 2023.

UCB, Inc. Rozanolixizumab-noli (Rtiggo) labeling. Available at: Microsoft Word - RYSTIGGO COL Rev. 06-2023(2).docx (ucb-usa.com). 06/2023. Accessed August 4, 2023.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs @ FDA. Rozanolixizumab-noli (Rystiggo). Package insert. [FDA Web site]. 06/26/2023. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. Accessed August 4, 2023.

Coding

CPT Procedure Code Number(s)

N/A

ICD - 10 Procedure Code Number(s)

N/A

ICD - 10 Diagnosis Code Number(s)

G70.00 Myasthenia gravis without (acute) exacerbation

G70.01 Myasthenia gravis with (acute) exacerbation

HCPCS Level II Code Number(s)

J9333 Injection, rozanolixizumab-noli, 1 mg

Revenue Code Number(s)

N/A

MPMiscCodesNarrativesPub

Coding and Billing Requirements

Cross Reference

Policy History

Revisions From 08.02.08a:

05/28/2025	The policy has been reviewed and reissued to communicate the Company's continuing position on rozanolixizumab-noli (Rystiggo).
05/29/2024	The policy has been reviewed and reissued to communicate the Company's continuing position on rozanolixizumab-noli (Rystiggo)
01/02/2024	This version of the policy will become effective 01/02/2024. The following NOC codes have been removed from this policy and were replaced by the following HCPCS codes: REMOVED: C9399 Unclassified drugs or biologics AND J3590 Unclassified biologics REPLACED WITH: J9333 Injection, rozanolixizumab-noli, 1 mg

05/28/2025

The policy has been reviewed and reissued to communicate the Company's continuing position on rozanolixizumab-noli (Rystiggo).

05/29/2024

The policy has been reviewed and reissued to communicate the Company's continuing position on rozanolixizumab-noli (Rystiggo)

01/02/2024

This version of the policy will become effective 01/02/2024.

The following NOC codes have been removed from this policy and were replaced by the following HCPCS codes:

REMOVED: C9399 Unclassified drugs or biologics AND J3590 Unclassified biologics

REPLACED WITH: J9333 Injection, rozanolixizumab-noli, 1 mg

Revisions From 08.02.08:

10/09/2023

This version of the policy will become effective 10/09/2023.

This new policy has been issued to communicate the Company’s coverage position and criteria for Rozanolixizumab-noli (Rystiggo).

Version Effective Date:

1/1/2024

Version Issued Date:

1/2/2024

Version Reissued Date:

5/28/2025