ModifiedUnitedHealthcarePolicy CSLA2O24DO04IU

Complement Inhibitors (Soliris, Ultomiris, PiaSky) — Medical Benefit Drug Policy (Louisiana)

Medical benefit drug policy governing use of complement inhibitors (eculizumab, ravulizumab, crovalimab) for UnitedHealthcare Community Plan members in Louisiana; defines covered indications, criteria for initial and continuation therapy, and applicable codes.

Policy Summary

PayerUnitedHealthcare

PolicyComplement Inhibitors (Soliris, Ultomiris, PiaSky) — Medical Benefit Drug Policy (LA)

Policy CodePolicy CSLA2O24DO04IU

Change TypeAdded PiaSkyrevised PNH and coding updates

Effective DateApr 1, 2025

Next Review Date

Key ActionObtain prior authorization with documentation of diagnosis, prior therapy history, FDA-label dosing, prescriber specialty, and required clinical response for initial or continuation requests.

SourceLink

POLICY UPDATE CHANGES

Added PiaSky (crovalimab-akkz) to the list of applicable complement inhibitor drug products.

Specified PiaSky is unproven and not medically necessary for STEC-HUS and is proven and medically necessary for PNH when criteria are met.

Revised coverage criteria for initial therapy for Soliris and Ultomiris for PNH; removed requirement that patient be treatment naive to both Soliris and Ultomiris.

Updated list of applicable HCPCS codes: added J1299 and J1307 and removed J1300.

Added prescriber requirement that PiaSky be prescribed by or in consultation with a hematologist or oncologist and initial authorization limit of no more than 12 months.

4major labeled indications with criteria

12 monthsinitial/reauthorization period

J1299,J1303,J1307

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PNH: provenPiaSky coverage status

UnprovenSTEC-HUS stance

Coverage Criteria for Complement Inhibitors

aHUS (Initial Therapy)

Soliris and Ultomiris are covered for atypical Hemolytic Uremic Syndrome (aHUS) when ALL of the following are met

aHUS initial therapy: Documentation supporting the diagnosis of aHUS by ruling out STEC-HUS and TTP (e.g., rule out ADAMTS13 deficiency); laboratory results, signs, and/or symptoms attributed to aHUS (e.g., thrombocytopenia, microangiopathic hemolysis, thrombotic microangiopathy, acute renal failure); Soliris or Ultomiris dosed according to U.S. FDA labeled dosing for aHUS; patient is treatment naive to both Soliris and Ultomiris; prescribed by, or in consultation with, a hematologist or nephrologist; initial authorization for no more than 12 months.

aHUS (Continuation Therapy)

Continuation therapy for aHUS

aHUS continuation: Documentation demonstrating positive clinical response from baseline (e.g., reduction of plasma exchanges, reduction of dialysis, increased platelet count, reduction of hemolysis); patient has previously been treated with Soliris or Ultomiris; Soliris or Ultomiris dosed according to U.S. FDA labeled dosing for aHUS; reauthorization for no more than 12 months; prescribed by, or in consultation with, a hematologist or nephrologist.

PNH (Initial Therapy)

PiaSkye, Soliris, or Ultomiris are covered for Paroxysmal Nocturnal Hemoglobinuria (PNH) when ALL of the following are met

PNH initial therapy: Flow cytometry confirming presence of PNH clones; laboratory results, signs, and/or symptoms attributed to PNH (e.g., abdominal pain, anemia, dyspnea, fatigue, smooth muscle dystonia, unexplained thrombosis, hemolysis/hemoglobinuria, kidney disease, pulmonary hypertension); PiaSkye, Soliris, or Ultomiris dosed according to U.S. FDA labeled dosing for PNH; history of trial and failure, contraindication, or intolerance to specified alternatives (for PiaSkye initial authorization: Empaveli (pegcetacoplan) or Soliris/Ultomiris AND Fabhalta (iptacopan)); patient not receiving PiaSkye in combination with a complement factor D inhibitor; patient not receiving Soliris/Ultomiris in combination with another C5 inhibitor, a C3 inhibitor, or a factor B inhibitor; prescribed by, or in consultation with, a hematologist or oncologist; initial authorization for no more than 12 months.

PNH (Continuation Therapy)

PNH continuation therapy

PNH continuation: Documentation demonstrating positive clinical response from baseline (e.g., increased or stabilized hemoglobin, reduction in transfusions, improvement in hemolysis, decreased LDH, increased reticulocyte count); patient previously treated with PiaSkye, Soliris, or Ultomiris; dosing per U.S. FDA labeled dosing for PNH; for PiaSkye only: not receiving PiaSkye, Soliris, or Ultomiris in combination with other complement inhibitors or factor B/D inhibitors; reauthorization for no more than 12 months; prescribed by, or in consultation with, a hematologist or oncologist.

gMG (Initial and Continuation Therapy)

Soliris and Ultomiris are covered for generalized myasthenia gravis (gMG) when ALL of the following are met

gMG initial therapy: Medical records confirming diagnosis of generalized myasthenia gravis; positive anti-AChR antibody serology; MG-ADL total score >= 6 at initiation; MGFA clinical classification II–IV at initiation; patient has not failed prior Soliris or Ultomiris; history of failure of at least two immunosuppressive agents over >=12 months OR failure of at least one immunosuppressive therapy plus >=4 courses of plasmapheresis/IVIG over >=12 months; Soliris or Ultomiris dosed per U.S. FDA labeled dosing for gMG; not receiving Soliris or Ultomiris in combination with another complement inhibitor or an FcRn blocker; prescribed by, or in consultation with, a neurologist; initial authorization <= 12 months.

gMG continuation: Patient previously treated with Soliris or Ultomiris; improvement and/or maintenance of at least a 2-point improvement in MG-ADL from baseline; maintenance, reduction, or discontinuation of baseline immunosuppressive therapy prior to starting therapy; reduction in signs and symptoms of myasthenia gravis; add-on or escalation of IST or additional rescue therapy from baseline considered treatment failure; dosing per label; not receiving prohibited combinations; reauthorization <= 12 months; prescribed by, or in consultation with, a neurologist.

NMOSD (Initial and Continuation Therapy)

Soliris and Ultomiris are covered for neuromyelitis optica spectrum disorder (NMOSD) when ALL of the following are met

NMOSD initial therapy: Diagnosis of NMOSD by a neurologist with qualifying clinical history (e.g., acute myelitis, optic neuritis, area postrema syndrome, symptomatic narcolepsy/diencephalic syndrome, acute brainstem syndrome, or symptomatic cerebral syndrome) and positive AQP4-IgG serology; other diagnoses (e.g., multiple sclerosis) ruled out; patient has not failed prior Soliris or Ultomiris; history of failure/contraindication/intolerance to rituximab AND either >=2 relapses in prior 12 months OR >=3 relapses in prior 24 months with >=1 in past 12 months; Soliris or Ultomiris dosed per U.S. FDA labeled dosing for NMOSD; not receiving prohibited combination therapies (disease modifying MS therapies, B-cell depletion, anti-IL6 therapy); prescribed by, or in consultation with, a neurologist; initial authorization <= 12 months.

NMOSD continuation: Patient previously treated with Soliris or Ultomiris; documentation of positive clinical response from baseline with reduction in number or severity of relapses or signs/symptoms; maintenance/reduction/discontinuation of baseline IST prior to starting therapy; not receiving prohibited combination therapies; dosing per label; reauthorization <= 12 months; prescribed by, or in consultation with, a neurologist.

Coverage-aligned clinical criteria

Covered when clinical diagnosis and study-aligned criteria are documented:

aHUS (ravulizumab/eculizumab): Diagnosis of aHUS with thrombocytopenia (platelet count <150 x10^9/L), evidence of hemolysis (elevated LDH), and renal impairment (elevated serum creatinine or dialysis requirement); trials required meeting each component of complete TMA response at 2 assessments ≥28 days apart.see text

Complete TMA response endpoint required assessments ≥28 days apart in trials

PNH (ravulizumab/eculizumab/crovalimab): Diagnosis of PNH with evidence of active hemolysis (e.g., LDH ≥1.5x ULN) or clinical instability after prior therapy; vaccination against Neisseria meningitidis prior to initiation or documentation of prophylactic antibiotics is required; trials enrolled both complement-inhibitor–naive and eculizumab-stable cohorts.LDH ≥1.5x ULN in some trials

Trials included both complement-inhibitor–naive and eculizumab-stable cohorts

Generalized Myasthenia Gravis (ravulizumab/eculizumab):

PiaSky: Initial and Continuation Therapy

PiaSky (crovalimab-akkz) for PNH is covered when ALL of the following are met:

PiaSky initial therapy criteria: Documentation supporting diagnosis of PNH including flow cytometry confirming presence of PNH clones and laboratory results, signs, and/or symptoms attributed to PNH; dosed according to U.S. FDA labeled dosing for PNH; patient has history of trial and failure, contraindication, or intolerance to one of: Empaveli (pegcetacoplan), Fabhalta (iptacopan), Soliris (eculizumab), or Ultomiris (ravulizumab); not receiving PiaSky in combination with a complement factor D inhibitor; prescribed by, or in consultation with, a hematologist or oncologist; initial authorization for no more than 12 months.

PiaSky continuation of therapy: Patient previously treated with PiaSky; documentation demonstrating positive clinical response from baseline (e.g., increased or stabilized hemoglobin, reduction in transfusions, improvement in hemolysis, decreased LDH, increased reticulocyte count); PiaSky dosed per U.S. FDA labeled dosing; not receiving PiaSky in combination with other complement inhibitors or factor B/D inhibitors; prescribed by, or in consultation with, a hematologist or oncologist; reauthorization may be for more than 12 months.

Soliris and Ultomiris indications

Soliris (eculizumab) and Ultomiris (ravulizumab) indications and limitations:

FDA-indicated uses: Soliris: aHUS; PNH; generalized myasthenia gravis (AChR antibody-positive); NMOSD (AQP4 antibody-positive). Ultomiris: aHUS and PNH (age ≥1 month), gMG (AChR+), NMOSD (AQP4+). Limitations: neither is indicated for STEC-HUS; both increase risk of meningococcal infection and vaccination per ACIP is required prior to initiation when possible.

PiaSky, Soliris, and Ultomiris are considered not medically necessary for the treatment of Shiga toxin E. coli–related hemolytic uremic syndrome (STEC‑HUS). This policy reflects the document statement that these complement inhibitors are unproven for STEC‑HUS and therefore are not covered for that indication.

Patients who do not meet the diagnostic criteria used in pivotal trials (for example, absence of thrombocytopenia or lacking evidence of hemolysis and renal impairment in aHUS trials) are not represented by the cited evidence and therefore the trial-based effectiveness data may not apply to them. Documentation should confirm the study-aligned inclusion features (e.g., platelet count <150 x10^9/L, elevated LDH, and renal impairment where applicable) when using those trial results to support treatment decisions.

Soliris (eculizumab), Ultomiris (ravulizumab), and PiaSky (crovalimab‑akkz) are not indicated for the treatment of Shiga toxin E. coli–related hemolytic uremic syndrome (STEC‑HUS); the policy explicitly states these products are unproven and not medically necessary for STEC‑HUS. PiaSky is FDA‑approved and indicated for PNH in patients ≥13 years and ≥40 kg, but the policy specifically documents that PiaSky is unproven and not medically necessary for STEC‑HUS. Providers should follow FDA labeling and the policy’s coverage criteria for other indications.

Use of Soliris, Ultomiris, or PiaSky for STEC‑HUS is considered not medically necessary. The policy clarifies that these complement inhibitors are unproven for STEC‑HUS and therefore are excluded from coverage for that diagnosis.

A limitation noted in the evidence base is that eculizumab did not meet the primary endpoint in the referenced generalized myasthenia gravis trial when analyzed by the worst‑rank method; secondary and sensitivity analyses were inconsistent with the primary result, which the authors identified as an important study limitation.

The policy emphasizes that PiaSky is unproven and not medically necessary for STEC‑HUS. In addition, eculizumab is not FDA‑indicated for STEC‑HUS, and the available evidence for complement inhibitors in STEC‑HUS is limited; accordingly these agents are excluded for that indication.

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for PiaSky, Soliris, and Ultomiris. Requests must include relevant medical records and meet diagnosis-specific criteria. Initial authorizations are generally limited to ≤ 12 months; reauthorization requires documentation of continued benefit. Drugs must be dosed according to the U.S. FDA‑labeled dosing for the requested indication.

Applicable to: PiaSky (crovalimab‑akkz), Soliris (eculizumab), Ultomiris (ravulizumab‑cwvz)
Initial authorization ≤ 12 months; reauthorization ≤ 12 months (unless otherwise noted)
Prescriptions must be by, or in consultation with, the appropriate specialist (hematologist, oncologist, nephrologist, or neurologist as applicable)

Prior Authorization

Prior authorization: diagnosis confirmation and meningococcal vaccination

For PNH, documentation must confirm the diagnosis and meningococcal vaccination status (or documented prophylactic antibiotics when vaccination is not feasible). For aHUS, documentation must show exclusion of STEC‑HUS and TTP and include laboratory and clinical evidence supportive of aHUS.

Applicable Codes and Coding Details

Applicable HCPCS and ICD-10 Codesmixed

J1299	Injection, eculizumab, 2 mg
J1303	Injection, ravulizumab-cwvZ, 10 mg
J1307	Injection, crovalimab-akkz, 10 mg
D59.30	Hemolytic-uremic syndrome, unspecified
D59.32	Hereditary hemolytic-uremic syndrome
D59.39	Other hemolytic-uremic syndrome
D59.5	Paroxysmal nocturnal hemoglobinuria [Marchiafava-Micheli]
G36.0	Neuromyelitis optica [Devic]
G70.00	Myasthenia gravis without (acute) exacerbation
G70.01	Myasthenia gravis with (acute) exacerbation

Applicable HCPCS codes (policy updates)HCPCS

J1299	Not specified in chunk (added to applicable HCPCS codes list)
J1307	Not specified in chunk (added to applicable HCPCS codes list)
J1300	Removed from applicable HCPCS codes list (quarterly edit)

MG-ADL score — threshold required at initiation

MG-ADL threshold>= 6 at initiation of therapy (MG-ADL total score)

Serologic requirementPositive anti‑AChR antibody test at initiation

Clinical classificationMGFA class II–IV at initiation

Study relapse criteria — relapse history and EDSS threshold for NMOSD eligibility

Relapse history requirementHistory of >=2 relapses in prior 12 months OR >=3 relapses in prior 24 months with >=1 relapse within the prior 12 months

Disability thresholdExpanded Disability Status Scale (EDSS) score <= 7 at enrollment

Definitions and Key Terms

Mechanism of action — terminal complement inhibition

MechanismMonoclonal antibodies bind complement protein C5 and inhibit its cleavage to C5a and C5b, preventing formation of the terminal complement complex (C5b‑9)

Resulting effectInhibits terminal complement–mediated intravascular hemolysis in PNH and prevents complement‑mediated thrombotic microangiopathy in aHUS

AgentsEculizumab, ravulizumab, and crovalimab act via terminal complement inhibition

Complete TMA response definition

Complete TMA response definitionNormalization of platelet count and lactate dehydrogenase (LDH) and >=25% improvement in serum creatinine from baseline, each met at 2 separate assessments >=28 days apart

Assessment timingCriteria must be satisfied at two assessments obtained at least 4 weeks (28 days) apart

Background and Clinical Evidence

Eculizumab, ravulizumab, and crovalimab bind complement protein C5, preventing its cleavage and blocking formation of the terminal complement complex. This terminal complement blockade inhibits terminal complement–mediated intravascular hemolysis and is the shared mechanism of action underlying their use in conditions such as aHUS and PNH. The policy background states these agents produce complete and sustained C5 inhibition in treated patients.

Policy Revision History

2025-04-01policy revisionLatest

Added PiaSky (crovalimab-akkz) to the list of applicable complement inhibitor products and specified PiaSky is proven for PNH when criteria are met and unproven/not medically necessary for STEC-HUS.

2025-04-01policy revision

Added prescriber requirement that PiaSky be prescribed by or in consultation with a hematologist or oncologist and limited initial authorization to no more than 12 months (continuation/reauthorization provisions also described).

2025-04-01

Policy Summary

PayerUnitedHealthcare

PolicyComplement Inhibitors (Soliris, Ultomiris, PiaSky) — Medical Benefit Drug Policy (LA)

Policy CodePolicy CSLA2O24DO04IU

Change TypeAdded PiaSkyrevised PNH and coding updates

Effective DateApr 1, 2025

Next Review Date

SourceLink

On This Page

Confirmed generalized MG with MG-ADL score ≥6 at baseline; prior therapies and disease severity per study protocols documented; vaccination against Neisseria meningitidis required in trials.

Trials required vaccination against Neisseria meningitidis

NMOSD (ravulizumab): AQP4-IgG seropositive NMOSD documented; ravulizumab weight-based dosing with maintenance every 8 weeks used in trials and compared to external comparator PREVENT.AQP4+ status

Ravulizumab dosing was weight-based with maintenance every 8 weeks; trials used external comparator PREVENT

PNH: Flow cytometry confirming PNH clones; documentation of clinical signs/symptoms and LDH where indicated; documentation of meningococcal vaccination prior to initiating complement inhibitor therapy or documented prophylactic antibiotics until vaccination effective

aHUS: Evidence that STEC‑HUS has been ruled out and ADAMTS13 deficiency/TTP has been ruled out; laboratory evidence such as thrombocytopenia, microangiopathic hemolysis, elevated LDH, and renal impairment

Denial Risk

Denial Triggers

Incomplete or missing documentation, failure to rule out alternative diagnoses, or dosing not consistent with FDA labeling are common denial triggers.

Missing diagnostic documentation (e.g., absent flow cytometry for PNH)
Failure to document that STEC‑HUS and TTP/ADAMTS13 deficiency were excluded for aHUS
Absent or outdated meningococcal vaccination documentation or lack of documented antibiotic prophylaxis when vaccination cannot be given
Laboratory data missing (e.g., LDH, platelet count, creatinine/eGFR, hemoglobin, reticulocyte count, MG‑ADL scores when applicable)
Dosing or schedule not consistent with the U.S. FDA‑labeled dosing for the requested indication
Missing documentation of prior therapy trials, failures, contraindications, or intolerances when step therapy is required

Note

Diagnostic inclusion criteria for aHUS trials

Clinical trial inclusion criteria referenced in aHUS ravulizumab studies may guide documentation expectations for diagnosis and severity.

Study criteria examples: platelet count < 150 x 10^9/L, evidence of hemolysis (e.g., elevated LDH), and serum creatinine above ULN or dialysis requirement
Requirement for ≥ 2 separate assessments at least 28 days apart demonstrating hematologic and renal response in trial endpoints — supports the need for serial laboratory documentation in clinical practice

Documentation Required

Documentation for PiaSky initial therapy

PiaSky initial authorization requires specific diagnostic and prior‑therapy documentation; failure to provide these may result in denial.

Flow cytometry analysis confirming presence of PNH clones is required for initial PiaSky authorization
Laboratory results and clinical signs/symptoms attributable to PNH (e.g., hemolysis/hemoglobinuria, abdominal pain, unexplained thrombosis, anemia, fatigue, pulmonary hypertension) must be submitted
Documentation of trial and failure, contraindication, or intolerance to required alternatives (see step‑therapy callout) must be provided at initial request
Prescriber requirement: PiaSky must be prescribed by, or in consultation with, a hematologist or oncologist

Documentation Required

Required Documentation

Submit complete medical records that demonstrate the indication, baseline disease severity, and prior therapies. Include objective lab values and disease‑specific scales when relevant.

General required documentation: chart notes, lab values (LDH, platelet count, hemoglobin, creatinine/eGFR, reticulocyte count), imaging/results if applicable, and documentation of clinical signs and symptoms attributed to the diagnosis
For gMG: baseline MG‑ADL total score and MGFA clinical classification at therapy initiation, and follow‑up MG‑ADL scores for continuation requests
For PNH: flow cytometry confirming PNH clones (initial), LDH and transfusion history, and documentation of prior therapy trials/failures/contraindications/intolerances
For aHUS: serial laboratory assessments (platelet count, LDH, creatinine/eGFR) and documentation ruling out STEC‑HUS and ADAMTS13 deficiency/TTP

Prior Authorization

PNH enrollment and meningococcal vaccination

PNH authorization requires evidence of active hemolysis and documentation of meningococcal vaccination status consistent with clinical trial and labeling practices.

Documentation of LDH ≥ 1.5 × ULN or other evidence of active hemolysis for patients aligning with Study 301 enrollment criteria is expected when applicable
Document meningococcal vaccination prior to initiation or documented use of prophylactic antibiotics until vaccination is effective; note whether vaccination was given on or before treatment start
For patients switching from or previously treated with complement inhibitors, provide prior treatment records and rationale for change

Step Therapy

Step Therapy for PNH (including PiaSky)

Step‑therapy requirements apply for PNH and for PiaSky specifically — provide evidence of trial and failure, contraindication, or intolerance to specified alternatives before authorization is approved.

PNH step therapy: Trial and failure, contraindication, or intolerance to listed alternatives is required (examples below)
PiaSky step requirement (initial therapy): Trial and failure, contraindication, or intolerance to at least one of: Empaveli (pegcetacoplan), Fabhalta (iptacopan), or a C5 inhibitor (Soliris or Ultomiris)
Do not co‑administer PiaSky with a complement factor D inhibitor or combine complement inhibitors with overlapping mechanism unless documented rationale and review provided

Note

Prior therapy considerations

Prior therapy context should include duration, response, and reason for discontinuation to substantiate a trial and failure or intolerance claim.

Document prior agent, dates of therapy, objective measures of response (e.g., hemoglobin, transfusion requirements, LDH), and reason for discontinuation (lack of efficacy, adverse event, contraindication)
When switching agents, include rationale (inadequate response, adverse effects, convenience) and any comparative data available in the chart to support medical necessity for the requested agent

Study contextCriteria derived from PREVENT trial inclusion for AQP4‑IgG–positive NMOSD

Use in trialsPrimary endpoint in ravulizumab aHUS phase 3 single‑arm study

Breakthrough hemolysis (study definition)

Breakthrough hemolysis (study definition)At least one new or worsening sign or symptom of intravascular hemolysis in the presence of LDH >= 2x upper limit of normal (ULN) after prior reduction of LDH to < 1.5x ULN on treatment

ContextDefined as a secondary efficacy endpoint in crovalimab (PiaSky) PNH trials

Relation to controlAssessed alongside hemolysis control (LDH <1.5x ULN) and transfusion avoidance endpoints

REMS — REMS program enrollment required for PiaSky, Soliris, and Ultomiris

REMS enrollmentRisk Evaluation and Mitigation Strategy (REMS) program enrollment is required for PiaSky, Soliris, and Ultomiris

Infection risk managementVaccinate against Neisseria meningitidis at least 2 weeks prior to initiation when possible and follow ACIP recommendations

MonitoringClosely monitor for early signs of meningococcal infection and evaluate immediately if suspected

AQP4+ NMOSD — neuromyelitis optica spectrum disorder with anti-aquaporin-4 antibody positivity

DefinitionNeuromyelitis optica spectrum disorder with anti‑aquaporin‑4 (AQP4) antibody positivity (AQP4+ NMOSD)

Clinical featuresQualifying history includes acute myelitis, optic neuritis, area postrema syndrome, brainstem syndrome, symptomatic narcolepsy/diencephalic syndrome, or symptomatic cerebral syndrome

Diagnostic requirementPositive AQP4‑IgG serology with alternative diagnoses (e.g., multiple sclerosis) ruled out

Revised PNH coverage criteria for Soliris and Ultomiris by removing the requirement that patients be treatment-naive to both agents.

2025-04-01coding update

Updated applicable HCPCS codes: added J1299 and J1307 and removed J1300 from the policy's code list.

Material changes effective 04/01/2025 include addition of PiaSky (crovalimab‑akkz) to the policy; designation that PiaSky is proven and medically necessary for PNH when criteria are met but unproven and not medically necessary for STEC‑HUS; updated coverage criteria for PNH initial therapy removing the prior requirement that patients be treatment naive to both Soliris and Ultomiris; updated HCPCS coding (added J1299 and J1307, removed J1300); and a new prescriber requirement that PiaSky be prescribed by or in consultation with a hematologist or oncologist with an initial authorization limit of no more than 12 months.