CurrentCareSourcePolicy N/A

Complement Inhibitors - Ultomiris Utilization Management Medical Policy

Defines CareSource prior authorization, coverage criteria, dosing, and contraindicated combinations for Ultomiris (intravenous ravulizumab) across FDA‑approved indications (aHUS, gMG, NMOSD, PNH) for medical benefit coverage.

Policy Summary

PayerCareSource

PolicyComplement Inhibitors - Ultomiris Utilization Management Medical Policy

Policy CodePolicy N/A

Change TypeRevised — added NMOSDreorganized concomitant use prohibitionsremoved subcutaneous references

Effective DateN/A

Next Review DateSep 25, 2024

Key ActionObtain prior authorization and document indication-specific diagnostic and specialist consultation requirements (e.g., AQP4 or anti‑AChR antibody positivity, neurologist/hematologist/nephrologist consults) to support approval.

SourceLink

POLICY UPDATE CHANGES

Neuromyelitis Optica Spectrum Disorder was added as a covered condition with criteria for approval.

Conditions not recommended for approval were expanded and reorganized to separate concomitant use prohibitions into distinct criteria (complement inhibitors except danicopan, rituximab/neonatal FcR blockers, Enspryng/Uplizna).

All references to subcutaneous Ultomiris were removed because the subcutaneous formulation will not be marketed.

For PNH continuing therapy, FACIT‑Fatigue improvement was added as an example of clinical benefit supporting ongoing approval.

4FDA‑approved indications covered

1 yrTypical approval duration (NMOSD, aHUS)

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Coverage Criteria and Authorization Rules

FDA‑Approved Indications (Initial and Continuation Therapy)

Coverage of Ultomiris is recommended when the patient meets the indication-specific criteria shown below.

Atypical Hemolytic Uremic Syndrome (aHUS) - Initial Therapy: Approve for 1 year if BOTH A and B are met

A) Patient does not have Shiga toxin Escherichia coli–related hemolytic uremic syndrome; B) Medication prescribed by or in consultation with a nephrologist.

aHUS Dosing: Approve one of the following weight-based regimens

A) ≥ 5 kg to < 20 kg: ≤ 600 mg IV one dose, then ≤ 600 mg IV every 4 weeks; B) ≥ 20 kg: ≤ 3,000 mg IV one dose, then ≤ 3,600 mg IV every 8 weeks.

Generalized Myasthenia Gravis (gMG): Approve when either Initial Therapy or Currently Receiving criteria are met

Initial: Approve for 6 months if ALL i–vii are met (i. ≥ 18 years; ii. confirmed anti‑acetylcholine receptor antibody–positive generalized myasthenia gravis; iii. MGFA class II–IV and MG‑ADL total score ≥ 6; iv. patient previously received or currently receiving pyridostigmine or has inadequate efficacy/contraindication/intolerance to pyridostigmine; v. patient previously received or currently receiving two different immunosuppressant therapies for ≥ 1 year or had inadequate efficacy/contraindication/intolerance to two immunosuppressants; vi. evidence of unresolved symptoms (e.g., difficulty swallowing, breathing, or functional disability); vii. prescribed by or in consultation with a neurologist). Currently Receiving: Approve for 1 year if (i. ≥ 18 years; ii. prescriber attests patient continues to derive benefit; iii. prescribed by or in consultation with a neurologist).

gMG Dosing: For patients ≥ 40 kg: ≤ 3,000 mg IV one dose, then ≤ 3,600 mg IV every 8 weeks

Neuromyelitis Optica Spectrum Disorder (NMOSD): Approve when either Initial Therapy or Currently Receiving criteria are met

Initial: Approve for 1 year if ALL i–iii met (i. ≥ 18 years; ii. diagnosis confirmed by positive anti‑aquaporin‑4 antibody test; iii. prescribed by or in consultation with a neurologist). Currently Receiving: Approve for 1 year if (i. ≥ 18 years; ii. positive anti‑AQP4 antibody; iii. prescriber attests clinical benefit; iv. prescribed by or in consultation with a neurologist).

NMOSD Dosing: For patients ≥ 40 kg: ≤ 3,000 mg IV one dose, then ≤ 3,600 mg IV every 8 weeks

Paroxysmal Nocturnal Hemoglobinuria (PNH): Approve when either Initial Therapy or Currently Receiving criteria are met

Initial: Approve for 6 months if BOTH i and ii are met (i. Diagnosis confirmed by peripheral blood flow cytometry showing absence or deficiency of GPI‑anchored proteins on at least two cell lineages; ii. prescribed by or in consultation with a hematologist). Currently Receiving: Approve for 1 year if (i. prescriber attests patient continues to derive benefit — examples include stabilization of hemoglobin, decreased transfusion requirements or transfusion independence, reductions in hemolysis, improvement in FACIT‑Fatigue; ii. prescribed by or in consultation with a hematologist).

PNH Dosing: Approve one of the following weight-based regimens

A) ≥ 5 kg to < 20 kg: ≤ 600 mg IV one dose, then ≤ 600 mg IV every 4 weeks; B) ≥ 20 kg: ≤ 3,000 mg IV one dose, then ≤ 3,600 mg IV every 8 weeks.

Coverage of Ultomiris is not recommended for concomitant use with other therapies that target complementary pathways or overlapping immune mechanisms unless specifically allowed. In particular, concomitant use with another complement inhibitor is not recommended except for Voydeya (danicopan), which is expressly permitted. The policy lists examples of complement inhibitors (e.g., Empaveli/pegcetacoplan, Fabhalta/iptcopan, PiaSky/crovalimab, Soliris/eculizumab) to illustrate this prohibition. Requests for combinations outside these allowances may be denied.

Operationally, references to a subcutaneous formulation of Ultomiris have been removed because the subcutaneous product will not be marketed; Ultomiris is available as an intravenous formulation only. This removal clarifies that any prior mention of subcutaneous Ultomiris should not be used as an authorization basis.

Coverage is not recommended for circumstances that fall outside the specific Recommended Authorization Criteria listed in this policy. The clinical criteria (indication-specific eligibility, dosing, prescriber specialty, and required documentation) define the situations for which medical benefit approval is appropriate, and requests that do not meet those criteria are not recommended for approval.

These authorization criteria will be updated as new published data become available; providers should expect criteria revisions to reflect evolving evidence and regulatory changes.

Specific concomitant agents and class-level exclusions include: other complement inhibitors (examples: Empaveli/pegcetacoplan, Fabhalta/iptcopan, PiaSky/crovalimab, Soliris/eculizumab) — concomitant use is not recommended except for Voydeya (danicopan) — and biologics that target B cells or neonatal Fc receptor pathways, such as rituximab products and neonatal FcR blockers (examples: Rystiggo/rozanolixizumab, Vyvgart/efgartigimod and Vyvgart Hytrulo).

In addition, concomitant use with NMOSD‑targeted monoclonal antibodies Enspryng (satralizumab) or Uplizna (inebilizumab) is not recommended. These exclusions are intended to prevent unstudied or potentially duplicative immunomodulation; exceptions are limited to the specific allowance for danicopan and other scenarios explicitly described in the policy notes.

Billing, Dosing Thresholds, and Codes

Referenced billing guidance (not explicitly coded in policy)HCPCS

J1300

Placeholder code — document does not list explicit HCPCS; policy refers to medical benefit PA

Weight-based dosing thresholds

< 20 kg dosingFor patients ≥5 kg to <20 kg: ≤600 mg IV one dose, then ≤600 mg IV every 4 weeks.

≥ 20 kg dosingFor patients ≥20 kg: ≤3,000 mg IV one dose, then ≤3,600 mg IV every 8 weeks.

≥ 40 kg (adult) dosing noteFor patients ≥40 kg (per indication-specific dosing): ≤3,000 mg IV one dose, then ≤3,600 mg IV every 8 weeks.

Typical initial approval duration (aHUS, NMOSD)aHUS and NMOSD initial approvals: 1 year when criteria met.

Typical initial approval duration (gMG, PNH)gMG initial therapy and PNH initial therapy: 6 months (gMG initial) and 6 months (PNH initial) as specified for initial therapy; continuation approvals typically 1 year.

Actions Required from Ordering Providers

Prior Authorization

Prior Authorization Required

Prior Authorization is required for medical benefit coverage of Ultomiris. Approval is granted only when the patient meets the indication‑specific criteria and dosing described in the policy. Extended approvals may be granted if the patient continues to meet criteria. Requests for doses outside the established dosing will be reviewed case‑by‑case by a clinician (Medical Director or Pharmacist). Ultomiris must be prescribed by or in consultation with a specialist for the treated condition.

Step Therapy

gMG Step‑Therapy Expectations

For initial therapy of generalized myasthenia gravis (gMG), members must have tried and had inadequate response to or intolerance/contraindication to first‑line symptomatic therapy and immunosuppressants prior to approval of Ultomiris. Specifically, initial‑therapy approvals require evidence of prior or current pyridostigmine use OR documentation of intolerance/contraindication to pyridostigmine, AND prior or current use of two different immunosuppressant therapies for ≥ 1 year OR documentation of inadequate efficacy/intolerance/contraindication to two different immunosuppressants. Initial approvals for gMG are authorized for 6 months; continuation approvals (patients currently receiving Ultomiris) are authorized for 1 year when ongoing clinical benefit is documented.

Key Clinical Definitions and Thresholds

PNH diagnostic requirement (flow cytometry)

Required flow cytometry findingPeripheral blood flow cytometry demonstrating absence or severe deficiency of GPI-anchored proteins on at least two cell lineages.

Purpose of testConfirms clinical diagnosis of paroxysmal nocturnal hemoglobinuria (PNH).

Prescriber involvementDiagnosis must be accompanied by prescription by or consultation with a hematologist for initial therapy authorization.

gMG severity and authorization criteria

MGFA class requirementPatient must meet Myasthenia Gravis Foundation of America (MGFA) classification II–IV for authorization.

MG-ADL score requirementMyasthenia Gravis Activities of Daily Living (MG-ADL) total score ≥ 6 is required.

Background and Drug Information

Ultomiris (intravenous ravulizumab) is a terminal complement C5 inhibitor with FDA‑approved indications for atypical hemolytic uremic syndrome (aHUS), generalized myasthenia gravis (gMG) in anti‑AChR antibody–positive adults, neuromyelitis optica spectrum disorder (NMOSD) in AQP4‑antibody–positive adults, and paroxysmal nocturnal hemoglobinuria (PNH). Coverage is recommended when patients meet the indication‑specific authorization criteria in this policy.

Ultomiris carries a boxed warning for serious meningococcal infections and is available only through a restricted REMS program; prescribers must follow REMS requirements and ensure appropriate vaccination and counseling. The formulation referenced in this policy is the intravenous product only; all references to a subcutaneous Ultomiris formulation have been removed because the subcutaneous version will not be marketed.

Policy Revision History

2024-09-25Annual RevisionLatest

Removed all references to a subcutaneous Ultomiris formulation because it will not be marketed; policy name changed from 'Ultomiris Intravenous PA' to 'Ultomiris PA'.

2024-09-25Annual Revision

For PNH patients currently receiving therapy, 'improvement in FACIT‑Fatigue score' was added as an example of clinical benefit supporting continuation approval.

2024-04-10