CurrentCentenePolicy CP.PHAR.648

Rozanolixizumab-noli (Rystiggo) (PDF)

Clinical policy defining medical necessity criteria, prior authorization requirements, dosing limits, concurrent therapy exclusions, approval durations, and coding guidance for Rystiggo (rozanolixizumab-noli) for treatment of generalized myasthenia gravis in adults across Commercial, HIM, and Medicaid lines of business.

Policy Summary

PayerCentene

PolicyRozanolixizumab-noli (Rystiggo) (PDF)

Policy CodePolicy CP.PHAR.648

Change TypeFormulation, quantity limits, concurrent therapy list, approval duration

Effective DateDec 1, 2023

Next Review Date

Key ActionProvider must submit documentation supporting diagnosis, MG-ADL score, MGFA classification, antibody positivity, prior therapy failures or contraindications, current weight, and dosing; requests will be reviewed against listed approval criteria.

SourceLink

POLICY UPDATE CHANGES

Added new 420 mg/3 mL, 560 mg/4 mL, and 840 mg/6 mL volume formulations and updated all quantity limits to 1 vial.

Added Bkemv, Epysqli, and Zilbrysq to the list of therapies that Rystiggo should not be prescribed concurrently with.

Clarified that the required immunosuppressive therapy should be non-steroidal and extended approval durations for Medicaid and HIM from 6 to 12 months.

1FDA-approved Indication Covered

3Required prior therapy classes

1Required clinician specialty (neurologist)

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1Vial quantity limit per weekly dose

Coverage Summary

Policy overview: This clinical policy (CP.PHAR.648) is effective 12.01.23 with last review on 11.25 and defines medical necessity criteria for Rystiggo (rozanolixizumab-noli). Coverage stance: covered_with_criteria. FDA-approved indication: Rystiggo is indicated for treatment of generalized myasthenia gravis (gMG) in adults who are anti-AChR or anti-MuSK antibody positive. High-level dosing cycle: weight-based subcutaneous dosing once weekly for 6 weeks per treatment cycle with subsequent cycles administered based on clinical evaluation (cycles not to be initiated sooner than 63 days from start of prior cycle); dose tiers are weight-based as specified in the dosing section.

Key thresholds & quick facts

MG-ADL baseline>= 3 from non-ocular symptoms

Response threshold (continuation)>= 2-point reduction in MG-ADL total score from baseline

Required prior therapy classes1) Cholinesterase inhibitor (if anti-AChR+), 2) Corticosteroid, 3) At least one non-steroidal immunosuppressive therapy

Required specialistPrescribed by or in consultation with a neurologist

Vial quantity limit per weekly dose1 vial

Approval duration by line of businessMedicaid/HIM: 12 months; Commercial: 6 months or to member renewal date, whichever is longer

Initial Therapy Criteria — Generalized Myasthenia Gravis

Step Therapy

Step therapy requirement (initial failure of prior therapies)

Initial approval requires documented failure of specified prior therapies (cholinesterase inhibitor if anti-AChR positive, corticosteroid, and at least one non-steroidal immunosuppressive therapy) unless contraindicated or adverse effects. Illinois HIM requests have a step therapy bypass per IL HB 5395 effective 2026-01-01.

Failure of a cholinesterase inhibitor if anti-AChR antibody positive (unless contraindicated or clinically significant adverse effects).
Failure of a corticosteroid (unless contraindicated or clinically significant adverse effects).
Failure of at least one non-steroidal immunosuppressive therapy (unless contraindicated or clinically significant adverse effects).
IL HIM step therapy bypass per IL HB 5395 effective 2026-01-01.

Prior Authorization

Documentation required for prior authorization

Provider must submit documentation supporting diagnosis and that approval criteria are met. Required documents include office chart notes, lab results or other clinical information demonstrating MG-ADL score and MGFA classification, antibody positivity, prior therapy failures or contraindications, current weight, and dosing.

Continuation / Renewal Criteria

Documentation Required

Clinical response for continuation

For continuation, document a positive clinical response defined as a 2-point reduction in MG-ADL total score from baseline.

Document 2-point reduction in MG-ADL total score from baseline

Denial Risk

Concurrent therapy exclusion

Claims may be denied if Rystiggo is prescribed concurrently with specified complement or antibody-directed therapies.

Vyvgart
Vyvgart Hytrulo
Soliris
Bkemv
Epysqli

Other Diagnoses / Off‑Label Uses

III. Other diagnoses/indications

When requested use is not for gMG or not covered by this policy:

ANY of the following

If this drug has recently (within the last 6 months) undergone a label change that is not yet reflected in this policy, follow applicable formulary/no-coverage or non-formulary policies as specified for the relevant line of business (CP.CPA.190, HIM.PA.33, CP.PMN.255, HIM.PA.103, CP.PMN.16).
If the requested use is not specifically listed under section III and criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business (CP.CPA.09, HIM.PA.154, CP.PMN.53).

IV. Diagnoses/Indications NOT authorized: Coverage is not authorized for non-FDA approved indications that are not addressed in this policy unless there is sufficient documentation of efficacy and safety per the applicable off-label use policies. If a requested use is not specifically listed under section III or the drug label has recently changed, refer to the formulary/no-coverage or non-formulary policies or the off-label use policy for the relevant line of business (CP.CPA.190, HIM.PA.33, CP.PMN.255; CP.CPA.190, HIM.PA.103, CP.PMN.16; or CP.CPA.09, HIM.PA.154, CP.PMN.53 as applicable).

Applicable Codes

HCPCS codes (informational)HCPCS

J3590	Unclassified biologics
C9399	Unclassified drugs or biologicals

Provider Actions & Billing Impact

Prior Authorization

Documentation required for prior authorization

Office chart notes documenting diagnosis and neurologist involvement
MG-ADL baseline score (≥ 3 from non-ocular symptoms) and MGFA classification (Class II–IVa)
Serologic test results showing anti-AChR or anti-MuSK antibody positivity
Documentation of prior therapy failures or contraindications (cholinesterase inhibitor, corticosteroid, non-steroidal immunosuppressant)
Current weight (kg) and proposed dosing

Billing Rule

Quantity limit per dose

Clinical Evidence

MycarinGKey phase 3 trial: MycarinG (randomized double‑blind placebo‑controlled, Lancet Neurol. 2023)

PI Mar 2025Prescribing information: Rystiggo Prescribing Information, UCB; March 2025

Vials:4Product availability: single‑dose vials 280 mg, 420 mg, 560 mg, 840 mg (140 mg/mL)

Dose wgtWeight‑based weekly SC dosing: <50 kg=420 mg; 50–<100 kg=560 mg; ≥100 kg=840 mg (max 1 vial/week for initial 6 weeks)

Evidence summary: Key evidence includes the MycarinG randomized, double-blind, placebo-controlled phase 3 trial (Lancet Neurol. 2023) and the Rystiggo Prescribing Information from UCB (March 2025). The policy references MycarinG as the pivotal phase 3 study supporting efficacy and safety. Definitions used in the evidence and policy: the MG-ADL is an 8-item patient-reported scale and a 2-point decrease is considered clinically meaningful; MGFA refers to the Myasthenia Gravis Foundation of America clinical classification (Class II to IVa required for initiation).

Background

Background: Rystiggo (rozanolixizumab-noli) is a neonatal Fc (FcRn) receptor blocker. The FDA-approved indication is for treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-AChR or anti-MuSK antibody positive. Dosing summary: initial treatment is weight-based subcutaneous administration once weekly for 6 weeks per cycle with weight-tiered doses (420 mg for weight < 50 kg; 560 mg for 50 to < 100 kg; 840 mg for ≥ 100 kg); subsequent treatment cycles are given based on clinical evaluation. Product availability includes single-dose vials at the specified strengths and volumes.

Revision History

4Q2024formulation_and_quantity_update

Added new vial formulations (420 mg/3 mL, 560 mg/4 mL, 840 mg/6 mL) and updated quantity limits to 1 vial (material change).

4Q2024concurrent_therapy_exclusion_added

Added Bkemv, Epigslist/ Epysqli, and Zilbrysq to the list of therapies that Rystiggo should not be prescribed concurrently with (material change).

4Q2025criteria_revisionLatest

Policy Summary

PayerCentene

PolicyRozanolixizumab-noli (Rystiggo) (PDF)

Policy CodePolicy CP.PHAR.648

Change TypeFormulation, quantity limits, concurrent therapy list, approval duration

Effective DateDec 1, 2023

Next Review Date

SourceLink

On This Page

Office chart notes documenting diagnosis and neurologist involvement
MG-ADL baseline score (≥ 3 from non-ocular symptoms) and MGFA classification (Class II–IVa)
Serologic test results showing anti-AChR or anti-MuSK antibody positivity
Documentation of prior therapy failures or contraindications (cholinesterase inhibitor, corticosteroid, non-steroidal immunosuppressant)
Current weight (kg) and proposed dosing

Billing Rule

Quantity limit per dose

Limit dosing to one vial per weekly dose. Dosing must follow weight-based mg limits: 420 mg for <50 kg, 560 mg for 50 to <100 kg, and 840 mg for ≥100 kg.

One vial per weekly dose
Weight < 50 kg: 420 mg
Weight 50 kg to < 100 kg: 560 mg
Weight ≥ 100 kg: 840 mg

Limit dosing to one vial per weekly dose and follow the dosing cadence: once weekly for the first 6 weeks of every 9-week cycle. Ensure dose does not exceed weight-based mg limits.

Once weekly for the first 6 weeks of every 9-week cycle
One vial per weekly dose

Denial Risk

Concurrent therapy exclusion

Claims may be denied if Rystiggo is prescribed concurrently with the following products.

Vyvgart
Vyvgart Hytrulo
Soliris
Bkemv
Epysqli
Ultomiris
Zilbrysq

Step Therapy

Step therapy requirement (initial failure of prior therapies)

Initial approval requires failure of specified prior therapies (cholinesterase inhibitor if anti-AChR positive, corticosteroid, and at least one non-steroidal immunosuppressive therapy) unless contraindicated or adverse effects. Illinois HIM requests have a step therapy bypass per IL HB 5395 effective 2026-01-01.

Failure of a cholinesterase inhibitor if anti-AChR antibody positive (unless contraindicated or clinically significant adverse effects).
Failure of a corticosteroid (unless contraindicated or clinically significant adverse effects).
Failure of at least one non-steroidal immunosuppressive therapy (unless contraindicated or clinically significant adverse effects).
IL HIM step therapy bypass per IL HB 5395 effective 2026-01-01.

Documentation Required

Clinical response for continuation

For continuation, document a positive clinical response defined as a 2-point reduction in MG-ADL total score from baseline.

Document 2-point reduction in MG-ADL total score from baseline

Clarified that required immunosuppressive therapy must be non-steroidal; extended Medicaid and HIM approval durations from 6 to 12 months for chronic gMG; added step therapy bypass for Illinois HIM per IL HB 5395 effective 2026-01-01 (material change).