CurrentNeighborhood Health Plan of Rhode IslandPolicy N/A

Ultomiris (ravulizumab) coverage criteria

Defines clinical indications, continuation and exclusion criteria, and utilization management authority for Ultomiris (ravulizumab) medication requests for members; applies to providers submitting authorization requests to the payer's UM program.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyUltomiris (ravulizumab) coverage criteria

Policy CodePolicy N/A

Change TypeRoutine review — no material changes

Effective DateMay 31, 2024

Next Review DateMay 8, 2024

Key ActionSubmit prior authorization requests through Evolent/UM; continuation may be approved without full reauthorization if used within last year with no progression or intolerance and no added medications.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

2FDA-approved indications listed

1Dose limits stated

3Core policy sections

May 08, 2024Approval date

Coverage Criteria

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

inv-01: Accepted Indications

Covered when the following diagnosis-specific criteria are met:

Indication: Member has either hemolytic paroxysmal nocturnal hemoglobinuria (PNH) and Ultomiris (ravulizumab) is being used to decrease hemolysis OR atypical hemolytic uremic syndrome (aHUS) with evidence of hemolysis (LDH above normal OR haptoglobin below normal OR schistocytes on peripheral blood smear) with or without impaired renal function (serum creatinine above normal)

captures both listed indications

inv-13: Initial therapy

Initial approval requires diagnosis-specific evidence

Initial indication: PNH for reducing hemolysis OR aHUS with evidence of hemolysis (LDH above normal OR haptoglobin below normal OR schistocytes on peripheral smear) with or without impaired renal function (serum creatinine above normal)

Initial coverage aligned to listed indications

inv-02: Continuation Therapy

Continuation requests may be approved without full reauthorization when ALL of the following are met:

Continuation criteria: 1) Requested medication was used within the last year; 2) Member has not experienced disease progression and/or has had no intolerance to the requested medication; 3) Additional medication(s) are not being added to the continuation request

Exemption from full policy if all are true

Coverage is not provided when Ultomiris (ravulizumab) is requested after documented disease progression on the same regimen or following progression on other anti‑complement therapies (for example, eculizumab), since prior progression on these therapies precludes benefit from continuing or switching within the same mechanism of action. Requests demonstrating disease progression while on Ultomiris — defined as failure to achieve a rise in hemoglobin with ongoing need for blood transfusions — are also excluded. Additionally, Ultomiris is not indicated for treatment of Shiga toxin–producing E. coli–related hemolytic uremic syndrome (STEC‑HUS).

Use of Ultomiris for off‑label or investigational indications that are not supported by robust evidence is considered not medically necessary. Supporting evidence must be consistent with CMS‑recognized compendia or acceptable peer‑reviewed literature; reliance on uncontrolled case reports or meeting abstracts without a full published article is insufficient. Evaluation of evidence considers whether the patient population and regimen mirror those in the published studies, whether outcomes are clinically meaningful (per standards such as ASCO’s recommended thresholds), and whether study design appropriately addresses the clinical question.

Provider Actions and Authorization

Prior Authorization

Prior Authorization Required

Prior authorization is required for all medication requests for Ultomiris (ravulizumab). Evolent/UM must process and authorize requests prior to administration; medications not authorized by Evolent may be deemed not approvable and not reimbursable.

All initial and non-exempt continuation requests must be submitted to Evolent/UM for prior authorization.
Continuation requests may be exempt if the drug was used within the last year, the member has not experienced disease progression or intolerance to the medication, and no additional medications are being added to the continuation request.

Denial Risk

Exclusion / Denial Triggers

Requests will be denied if Ultomiris is used after disease progression on the same regimen or following progression on other anti-complement therapies (e.g., Soliris/eculizumab). Additional exclusion triggers include use for STEC-HUS, dosing that exceeds single-dose limits, and investigational/off-label uses lacking sufficient evidence per CMS-recognized compendia or acceptable peer-reviewed literature.

Use after disease progression on the same regimen or after other anti-complement therapies (e.g., eculizumab).
Disease progression while on Ultomiris defined by lack of hemoglobin response and continued need for transfusions.
Use for Shiga toxin E. coli–related HUS (STEC-HUS) is not indicated.
Dosing exceeding single dose limits: loading dose >3,000 mg or maintenance dose >3,600 mg.
Investigational or off-label indications without sufficient supporting evidence (see documentation criteria).

Denial Risk

Anti‑complement Prior Therapy Consideration

Ultomiris must not be initiated or continued in members who have had disease progression on other anti-complement therapies. Prior exposure to anti-complement agents (for example, eculizumab) with subsequent progression is a contraindication to approval.

Policy excludes use after progression on other anti-complement therapies such as Soliris (eculizumab).
Continuation is not allowed where the member experienced disease progression while receiving anti-complement therapy.

Documentation Required

Required Supporting Documentation

Support for medical necessity must come from one of the following: FDA-approved labeling, CMS-recognized compendia, NCCN or ASCO clinical guidelines, or acceptable peer‑reviewed literature that meets CMS Medicare Benefit Policy Manual Chapter 15 standards. Insufficient evidence (per criteria in policy) for off‑label or investigational uses is grounds for denial.

Acceptable sources: FDA labeling; CMS-recognized compendia; NCCN or ASCO guidelines; peer‑reviewed literature meeting CMS Chapter 15 requirements.
Insufficient evidence considerations include representativeness of patient population and regimen, clinically meaningful outcomes (ASCO guidance), and study design adequacy.

Coding and Dose Limits

Single dose limits — Ultomiris (ravulizumab)

Loading dose limit≤ 3,000 mg per single loading dose

Maintenance dose limit≤ 3,600 mg per single maintenance dose

Threshold sourcePolicy single dose limits specified in Exclusion Criteria D

Ultomiris (ravulizumab) — Quantity limits

Loading dose quantity limitUltomiris loading dose must not exceed 3,000 mg per single administration

Maintenance dose quantity limitUltomiris maintenance dose must not exceed 3,600 mg per single administration

ApplicabilityLimits apply to quantity/ dosing in medication requests per policy Exclusion Criteria D

Initial Therapy

inv-13: Initial therapy

Initial approval requires diagnosis-specific evidence

Initial coverage aligned to listed indications

Continuation and Renewal

inv-14: Continuation requests

Continuation/renewal exemption conditions

Continuation exemption: Medication used within last year; no disease progression and no intolerance to the medication; no additional medications added to the request

Allows continuation without full reauthorization if met

Step Therapy / Exclusions

Step	Requirement / Restriction	Coverage Status
1
Use after disease progression on other anti-complement agents (e.g., eculizumab) or after disease progression with the same regimen is excluded
See exclusion criteria III.A–B for definition of disease progression while on therapy

Administration and Site-of-Care

Note

Use FDA label/package insert for infusion center administration details

Refer to the FDA label/package insert for administration, infusion center procedures, and medication‑management details related to Ultomiris.

Follow FDA label/package insert for infusion administration and related management considerations.

Definitions

aHUS — policy definition

DefinitionAtypical hemolytic uremic syndrome (aHUS) with evidence of hemolysis

Evidence of hemolysisLDH above normal, haptoglobin below normal, or schistocytes on peripheral blood smear

Renal function considerationMay be present with or without impaired renal function (serum creatinine above normal)

PNH — policy definition

IndicationParoxysmal nocturnal hemoglobinuria (PNH) used to decrease hemolysis

Treatment goalReduction of hemolysis as the indicated therapeutic effect of Ultomiris

Policy contextPNH is a covered indication when Ultomiris is being used to decrease hemolysis

Background

Ultomiris (ravulizumab) is an anti‑complement C5 monoclonal antibody indicated to reduce hemolysis in members with paroxysmal nocturnal hemoglobinuria (PNH) and to treat atypical hemolytic uremic syndrome (aHUS) in patients with laboratory evidence of hemolysis. For aHUS, evidence of hemolysis may include elevated lactate dehydrogenase, low haptoglobin, or schistocytes on peripheral smear, with or without impaired renal function. Coverage and continuation decisions reference the FDA label and recognized compendia/guidelines and must align with the policy’s dosing limits and exclusion criteria.