CurrentEmblemHealthPolicy MG.MM.PH.187

Medical Policy: Ultomiris® (ravulizumab-cwvz)

Defines EmblemHealth medical policy coverage criteria, dosing limits, limitations/exclusions, applicable procedure/NDC/ICD-10 codes, and renewal durations for Ultomiris (ravulizumab-cwvz) across indications including PNH, aHUS, gMG, and Neuromyelitis Optica Spectrum Disorder (NMOSD).

Policy Summary

PayerEmblemHealth

PolicyMedical Policy: Ultomiris® (ravulizumab-cwvz)

Policy CodePolicy MG.MM.PH.187

Change TypeCriteria revisions and indication addition

Effective Date

Next Review Date

Key ActionTreating physician must submit clinical evidence that the member meets criteria for treatment (e.g., flow cytometry, antibody testing, documentation of benefit).

SourceLink

POLICY UPDATE CHANGES

Generalized Myasthenia Gravis criteria updated: MG-ADL threshold changed to > 6; requirement narrowed to pyridostigmine rather than broader prior immunosuppressants; removed prior requirement for two immunosuppressants.

Neuromyelitis Optica Spectrum Disorder indication and criteria (including ICD code G36.0 and NDC 25682-0022-01) were added.

PNH and aHUS prior numeric laboratory and transfusion-based criteria were removed (e.g., percent PNH type III red cells, LDH threshold, transfusion-dependence criteria).

Length of initial authorization updated: 6 months for aHUS and gMG; 12 months for PNH and NMOSD; renewals for 1 year.

Updated dosing limits per weight-based regimen across indications and updated HCPCS code to J1303 (effective 10/1/2019).

4Covered Indications

1Boxed Warning (meningococcal infection)

Coverage Summary

Scope: EmblemHealth policy status for Ultomiris (ravulizumab-cwvz) is covered_with_criteria for paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), anti‑AChR antibody‑positive generalized myasthenia gravis (gMG), and neuromyelitis optica spectrum disorder (NMOSD). The policy defines indication‑specific initial approval and renewal criteria, dosing limits, applicable procedure/NDC/ICD‑10 codes, and specialist prescriber requirements. Ultomiris carries a Boxed Warning for life‑threatening meningococcal infections and is available only through a REMS program; prescribers must be enrolled in REMS and follow the vaccination/prophylaxis guidance in the policy.

Initial Therapy Criteria (by indication)

Initial Approval Criteria - Paroxysmal Nocturnal Hemoglobinuria (PNH)

Approve if the patient meets ONE of the following (A or B):

A. Initial therapy

Diagnosis was confirmed by peripheral blood flow cytometry results showing the absence or deficiency of glycosylphosphatidylinositol (GPI)-anchored proteins on at least two cell lineages
The medication is prescribed by or in consultation with a hematologist
Patient is 1 month of age or older>= 1 month

B. Currently receiving Ultomiris (IV or subcutaneous)

Patient is continuing to derive benefit from Ultomiris (intravenous or subcutaneous), according to the prescriber
The medication is prescribed by or in consultation with a hematologist

Initial Approval Criteria - Atypical Hemolytic Uremic Syndrome (aHUS)

Approve if the patient meets ALL of the following (A, B, and C):

Patient does not have Shiga toxin E. coli related hemolytic uremic syndrome

Patient is at least one month of age or older and weighs ≥5 kgage >= 1 month; weight >= 5 kg

The medication is prescribed by or in consultation with a nephrologist

Initial Approval Criteria - Generalized Myasthenia Gravis (gMG)

Approve if the patient meets ONE of the following (A or B):

A. Initial therapy

Patient is ≥ 18 years of age>= 18 years
Patient has confirmed anti-acetylcholine receptor antibody positive generalized myasthenia gravisanti-AChR positive
Patient meets both of the following (a and b)
- a: Myasthenia Gravis Foundation of America classification of II to IVMGFA II-IV

Initial Approval Criteria - Neuromyelitis Optica Spectrum Disorder (NMOSD)

Approve for the duration noted if the patient meets ONE of the following (A or B):

A. Initial therapy

Patient is ≥ 18 years of age>= 18 years
Diagnosis was confirmed by a positive blood serum test for anti-aquaporin-4 antibodyanti-AQP4 positive
The medication is being prescribed by or in consultation with a neurologist

B. Currently receiving Ultomiris intravenous

Patient is ≥ 18 years of age

Continuation & Renewal Criteria

Renewal Criteria

All indications can be renewed for 1 year if renewal criteria are met per indication

Renewal allowed for 1 year (per policy statement). Note: renewal durations and initial authorization lengths vary by indication (initial: aHUS and gMG = 6 months; PNH and NMOSD = 12 months).

Limitations / Exclusions

Limitations / Exclusions (Not Medically Necessary)

Ultomiris is not considered medically necessary when any of the following selection criteria is met:

Patient is not currently receiving treatment and is asymptomatic or has mild symptoms (active surveillance appropriate)

Patient has unresolved Neisseria meningitidis

Patient is currently not vaccinated against N. meningitidis, unless the risks of delaying treatment outweigh the risks of developing a meningococcal infection

If vaccination cannot be given prior to first dose, provide 2 weeks of antibacterial prophylaxis and document rationale (per REMS/boxed warning).

Will be used in combination with other immunomodulatory biologic therapies (examples: efgartigimod, eculizumab, pegcetacoplan, satralizumab, inebilizumab, etc.)

Changes note: Recent revisions removed prior numeric laboratory and transfusion‑based thresholds and some specialist prescriber language for PNH and aHUS (for example, percent PNH type III red cells, LDH thresholds, and transfusion‑dependence criteria were eliminated). These removals narrow reliance on rigid numeric cutoffs and do not add new broad exclusions beyond the documented limitations (e.g., unresolved N. meningitidis, lack of meningococcal vaccination, asymptomatic patients appropriate for surveillance, or prohibited combination biologic therapies).

Applicable Codes

Covered HCPCSHCPCSCovered

J1303

Injection, ravulizumab-cwvz, 10 mg

Applicable NDCsNDCCovered

25682-0025-xx	Ultomiris 300 mg/3 mL single-dose vials for injection
25682-0028-xx	Ultomiris 1100 mg/11 mL single-dose vials for injection
25682-0022-xx	Ultomiris 300 MG/30ML

Relevant ICD-10 DiagnosesICD-10Covered

D59.5	Paroxysmal nocturnal hemoglobinuria [Marchiafava-Micheli]
D59.3	Hemolytic-uremic syndrome
G36.0	Neuromyelitis Optica
G70.00	Myasthenia gravis without (acute) exacerbation
G70.01	Myasthenia gravis with (acute) exacerbation

Provider Actions & Requirements

Documentation Required

Submit clinical evidence for medical necessity

Treating physician must submit clinical evidence that the member meets criteria for treatment. Examples: peripheral blood flow cytometry results for PNH; antibody testing (anti-AChR for gMG, anti–aquaporin-4 for NMOSD); documentation of clinical benefit for patients continuing therapy (examples: stabilization of hemoglobin, decreased transfusion requirements or transfusion independence, reductions in hemolysis).

Flow cytometry results demonstrating deficiency of GPI‑anchored proteins on ≥2 cell lineages (PNH).
Positive anti‑AChR antibody test (gMG) or positive anti‑aquaporin‑4 antibody test (NMOSD).
Documentation of derived clinical benefit for continuation (e.g., hemoglobin stabilization, reduced transfusions, fewer relapses or symptom improvement).

Prior Authorization

Clinical Evidence & Safety Notes

Evidence and safety: Ultomiris is a monoclonal antibody that binds complement protein C5 to inhibit its cleavage and prevent formation of the terminal complement complex; it is indicated for PNH, complement‑mediated TMA in aHUS, anti‑AChR antibody‑positive gMG, and NMOSD. The product has a REMS program requirement — prescribers must be enrolled to prescribe Ultomiris — and a Boxed Warning for life‑threatening meningococcal infections. The policy recommends meningococcal vaccination at least 2 weeks prior to the first dose when feasible; if therapy cannot be delayed, provide 2 weeks of antibacterial prophylaxis and document the rationale. Vaccination reduces but does not eliminate the risk of meningococcal infection, and vaccination should follow current ACIP guidance.

Definitions

Ultomiris: Monoclonal antibody that binds with high affinity to complement protein C5, inhibiting its cleavage to C5a and C5b and preventing generation of the terminal complement complex C5b9; used to inhibit terminal complement‑mediated intravascular hemolysis in PNH and complement‑mediated thrombotic microangiopathy in aHUS. Indications include PNH, aHUS, anti‑AChR antibody‑positive generalized myasthenia gravis (gMG), and neuromyelitis optica spectrum disorder (NMOSD).

Revision History

06/20/2024revisedLatest

Generalized Myasthenia Gravis criteria revised: removed prior requirement for two immunosuppressant therapies; MG-ADL threshold adjusted earlier (see 5/29/2024) and prescriber/therapeutic requirements narrowed (now specify pyridostigmine).

05/29/2024revised/added

Annual revision recorded 5/29/2024 reflecting changes from 1/2/2024 and 04/13/2023: MG-ADL threshold changed from ≥5 (or prior values) to > 6; NMOSD indication and full criteria (including ICD code G36.0 and NDC 25682-0022-01) added/confirmed; PNH and aHUS prior numeric laboratory and transfusion-based criteria were removed.

04/13/2023