UnitedHealthcare Complement Inhibitors Coverage Update

Medical Necessity Criteria by Indication

Atypical Hemolytic Uremic Syndrome (aHUS) — Initial Therapy

Bkemv, Epysqli, Soliris and Ultomiris are proven and medically necessary for aHUS when ALL of the following are met:

ALL of the following

Documentation supporting the diagnosis of aHUS by ruling out both 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)
Patient is treatment naïve with the requested product
Requested product is dosed according to the U.S. FDA labeled dosing for aHUS
Prescribed by, or in consultation with, a hematologist or nephrologist
Initial authorization will be for no more than 12 months

Atypical Hemolytic Uremic Syndrome (aHUS) — Continuation of Therapy

Continuation of therapy is proven and medically necessary when ALL of the following are met:

ALL of the following

Patient has previously been treated with the requested product
Documentation demonstrating a positive clinical response from baseline (e.g., reduction of plasma exchanges, reduction of dialysis, increased platelet count, reduction of hemolysis)
Requested product is dosed according to the U.S. FDA labeled dosing for aHUS
Prescribed by, or in consultation with, a hematologist or nephrologist
Reauthorization will be for no more than 12 months

Shiga toxin E. coli–related HUS (STEC-HUS)

Not covered / Unproven:

ALL of the following

Bkemv, Epysqli, Soliris and Ultomiris are unproven and not medically necessary for treatment of STEC-HUS

Paroxysmal Nocturnal Hemoglobinuria (PNH) — Initial Therapy

Bkemv, Epysqli, PiaSky, Soliris, and Ultomiris are proven and medically necessary for PNH when ALL of the following are met:

ALL of the following

Documentation supporting diagnosis of PNH including flow cytometry confirming PNH clones
Laboratory results, signs and/or symptoms attributed to PNH (e.g., abdominal pain, anemia, dyspnea, fatigue, hemolysis/hemoglobinuria, thrombosis, kidney disease, pulmonary hypertension)
Requested product is dosed according to U.S. FDA labeled dosing for PNH
PiaSky-specific requirements
- History of trial and failure, contraindication, or intolerance to one of: a complement C5 inhibitor (Bkemv, Epysqli, Soliris, Ultomiris) OR Empaveli (pegcetacoplan) OR Fabhalta (iptacopan)

Paroxysmal Nocturnal Hemoglobinuria (PNH) — Continuation of Therapy

Continuation criteria for PNH when ALL of the following are met:

ALL of the following

Patient has previously been treated with the requested product
Documentation demonstrating a positive clinical response from baseline (e.g., increased/stabilization of hemoglobin, reduction in transfusions, improvement in hemolysis, decrease in LDH, increased reticulocyte count)
Requested product is dosed according to U.S. FDA labeled dosing for PNH
Patient is not receiving the requested product in combination with: a different complement C5 inhibitor; a complement C3 inhibitor; a complement factor B inhibitor
Prescribed by, or in consultation with, a hematologist or oncologist

Generalized Myasthenia Gravis (gMG) — Initial Therapy

Bkemv, Epysqli, Soliris and Ultomiris are proven and medically necessary for anti-AChR antibody-positive gMG when ALL of the following are met:

ALL of the following

Medical records confirming patient has NOT failed a previous course of a complement C5 inhibitor (Bkemv, Epysqli, Soliris, Ultomiris, or Zilbrysq)
Diagnosis of generalized myasthenia gravis (gMG)
Positive serologic test for anti-AChR antibodies
MGFA Clinical Classification class II, III, or IV at initiation of therapy
MG-ADL total score >= 6 at initiation of therapy>= 6

Generalized Myasthenia Gravis (gMG) — Continuation of Therapy

Continuation criteria for gMG when ALL of the following are met:

ALL of the following

Patient has previously been treated with the requested product
Medical records demonstrating all of the following: improvement and/or maintenance of at least a 2-point improvement in MG-ADL from baseline; reduction in signs and symptoms of MG; maintenance, reduction, or discontinuation of baseline immunosuppressive therapy doses prior to starting the requested product>= 2-point improvement from baseline
Note: Add on, dose escalation of IST, or additional rescue therapy from baseline while on requested product will be considered treatment failure
Requested product is dosed according to the U.S. FDA labeled dosing for gMG

Neuromyelitis Optica Spectrum Disorder (NMOSD) — Initial Therapy

Bkemv, Epysqli, Soliris and Ultomiris are proven and medically necessary for NMOSD when ALL of the following are met:

ALL of the following

Diagnosis of NMOSD by a neurologist confirming relevant past medical history (optic neuritis, acute myelitis, area postrema syndrome, acute brainstem syndrome, symptomatic narcolepsy/diencephalic syndrome, or symptomatic cerebral syndrome with NMOSD-typical brain lesions)
Positive serologic test for anti-aquaporin-4 immunoglobulin G (AQP4-IgG)/NMO-IgG antibodies
Multiple sclerosis or other diagnoses have been ruled out
Patient has not failed a previous course of a complement C5 inhibitor for NMOSD
History of failure of, contraindication, or intolerance to rituximab therapy

Neuromyelitis Optica Spectrum Disorder (NMOSD) — Continuation of Therapy

Continuation criteria for NMOSD when ALL of the following are met:

ALL of the following

Patient has previously been treated with the requested product
Documentation of positive clinical response from baseline demonstrated by both: reduction in number and/or severity of relapses or signs/symptoms of NMOSD; and maintenance, reduction, or discontinuation of baseline immunosuppressive therapy doses prior to starting the requested product
Note: Add on, dose escalation of IST, or additional rescue therapy while on requested product will be considered treatment failure
Requested product is dosed according to the U.S. FDA labeled dosing for NMOSD
Prescribed by, or in consultation with, a neurologist

FDA Indications / Informational

Agents and their FDA-labelled indications (informational only; FDA approval alone is not a basis for coverage):

ANY of the following

Bkemv (eculizumab-aeeb): treatment of PNH; aHUS (patients ≥1 month) to inhibit complement-mediated TMA; generalized myasthenia gravis (gMG) in adults who are anti-AChR antibody positive.
Limitations: not indicated for STEC-HUS.
Epysqli (eculizumab-aagh): treatment of PNH; aHUS (patients ≥1 month); gMG (anti-AChR+).
Limitations: not indicated for STEC-HUS.
PiaSky (crovalimab): indicated for PNH in patients ≥13 years and ≥40 kg.
Increases risk of Neisseria meningitidis infection; vaccination required per ACIP guidance.
Soliris (eculizumab): PNH; aHUS; gMG (≥6 years) AChR+; NMOSD in adults who are anti-AQP4 antibody positive.

Vaccination / REMS requirements (provider obligations)

All agents in this class carry increased risk of meningococcal infection; REMS enrollment and vaccination guidance:

ALL of the following

Vaccinate for meningococcal disease per current ACIP recommendations prior to therapy when possible.
Immunize patients without prior meningococcal vaccination at least 2 weeks prior to first dose of Soliris or Ultomiris; if urgent therapy required, vaccinate as soon as possible.
Revaccinate in accordance with ACIP recommendations, considering treatment duration.
Enroll prescribers in the agent-specific REMS program prior to prescribing (contact numbers/URLs provided for each product).
Bkemv, Epysqli, PiaSky, Soliris, Ultomiris are REMS-restricted; enrollment is mandatory under REMS.
Monitor patients closely for early signs/symptoms of meningococcal infection and evaluate immediately if suspected.

Applicable Codes

HCPCS — drug injection codes referencedHCPCS

J1299	Injection, eculizumab, 2 mg
J1303	Injection, ravulizumab-cwvz, 10 mg
J1307	Injection, crovalimab-akkz, 10 mg
Q5151	Injection, eculizumab-aagh (epijkstra/epysqli), biosimilar, 2 mg
Q5152	Injection, eculizumab-aeeb (bkemv), biosimilar, 2 mg

ICD-10 Diagnosis codes referencedICD-10

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

Added HCPCS codesHCPCS

Q5151	Newly added HCPCS code (policy added to Applicable Codes section).
Q5152	Newly added HCPCS code (policy added to Applicable Codes section).

Authorization, Documentation, and Denial Risks

Prior Authorization

Authorization required with documentation

Initial and continuation use require documentation supporting the diagnosis and demonstration of clinical response; initial authorization and reauthorization periods are limited to no more than 12 months.

J1299
J1303
J1307
Q5151
Q5152

Documentation Required

Diagnosis-specific documentation requirements

Provide indication-specific diagnostic proof: for aHUS, documentation ruling out STEC-HUS and TTP (e.g., ADAMTS13 deficiency); for PNH, flow cytometry confirming PNH clones; for gMG, positive anti-AChR serology plus MGFA class II–IV and MG-ADL score ≥6; for NMOSD, positive AQP4-IgG and neurologist confirmation that MS and other diagnoses are ruled out.

Clinical and Mechanistic Background

Eculizumab, ravulizumab, and crovalimab are monoclonal antibodies that target complement protein C5, binding with high affinity to prevent its cleavage into C5a and C5b and thereby blocking formation of the terminal complement complex / membrane attack complex (C5b-9). This C5 blockade interrupts terminal complement–mediated processes such as intravascular hemolysis and thrombotic microangiopathy that underlie diseases like paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). (See U.S. FDA prescribing information for product-specific mechanisms and pharmacology.)

These agents have FDA-approved indications supported by clinical trial evidence for several conditions: aHUS (eculizumab and ravulizumab; indicated for adults and pediatric patients ≥1 month for some products), PNH (eculizumab, ravulizumab, crovalimab), generalized myasthenia gravis (gMG) with anti-AChR antibodies (eculizumab and ravulizumab), and neuromyelitis optica spectrum disorder (NMOSD) in AQP4‑IgG–positive adults (eculizumab and ravulizumab). The policy lists product-specific FDA indications for Bkemv (eculizumab‑aeeb) and Epysqli (eculizumab‑aagh) consistent with these same disease states.

All agents in this class carry an increased risk of invasive Neisseria meningitidis infection; REMS enrollment and adherence to current ACIP meningococcal vaccination and revaccination guidance are required prior to or at treatment initiation, and clinicians must monitor and evaluate patients promptly for signs of meningococcal disease.

The evidence is insufficient for STEC‑HUS: eculizumab is not indicated for Shiga toxin–producing E. coli–related HUS and available studies are few and inconclusive, so these complement C5 inhibitors are considered unproven and not medically necessary for treatment of STEC‑HUS in this policy.

Key Terms

Definitions

STEC-HUSShiga toxin-producing E. coli–related hemolytic uremic syndrome; must be ruled out for aHUS diagnosis.

TTPThrombotic thrombocytopenic purpura; ruled out for aHUS diagnosis (e.g., ADAMTS13 deficiency).

MG-ADLMyasthenia Gravis Activities of Daily Living scale — used to quantify symptom burden (score threshold used in criteria).

REMSRisk Evaluation and Mitigation Strategy — a program required by the FDA for certain drugs to ensure benefits outweigh risks; prescriber enrollment and specific safety measures (e.g., vaccinations) are commonly required.

AChRAcetylcholine receptor — patients who are anti-AChR antibody positive are eligible for certain gMG indications.

AQP4Aquaporin-4 — antibodies against AQP4 identify patients with NMOSD who may be eligible for therapy.

Clinical Thresholds Referenced

Key Thresholds

MG-ADL initiation (gMG)>= 6

MG-ADL improvement for continuation (gMG)>= 2-point improvement from baseline

MG-ADL clinical trial response definition>= 3-point improvement (clinical trial definition)

PNH LDH entry threshold (trial context)>= 1.5 × upper limit of normal (LDH)

aHUS platelet criteria (trial)Platelet count <= 150 x 10^9/L

Policy Changes and Updates

01/01/2026revisedLatest

Revised list of applicable complement inhibitor drug products and added Bkemv (eculizumab-aeeb) and Epysqli (eculizumab-aagh) as proven/medically necessary for aHUS, gMG (AChR+), NMOSD, and PNH.

01/01/2026revised

Replaced prior criterion language that named Soliris/Ultomiris specifically with broader language referencing 'a complement C5 inhibitor' (including Bkemv, Epysqli, Soliris, Ultomiris) for prior exposure/failure requirements across PNH, gMG, and NMOSD.

01/01/2026revised

OpenPayer

Complement Inhibitors (for Louisiana Only)

Medical Necessity Criteria by Indication

Applicable Codes

Authorization, Documentation, and Denial Risks

Clinical and Mechanistic Background

Key Terms

Clinical Thresholds Referenced

Policy Changes and Updates