UnitedHealthcare complement inhibitors Coverage Update

Coverage and Medical Necessity Criteria

inv-01: aHUS Initial Therapy

Covered when ALL of the following are met

aHUS initial therapy: 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 attributable to aHUS (e.g., thrombocytopenia, microangiopathic hemolysis, thrombotic microangiopathy, acute renal failure); patient is treatment‑naïve to Ultomiris; Ultomiris dosed according to U.S. FDA labeled dosing for aHUS; prescribed by, or in consultation with, a hematologist or nephrologist; initial authorization for no more than 12 months.

inv-02: aHUS Continuation Therapy

Covered when ALL of the following are met

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

inv-03: Paroxysmal Nocturnal Hemoglobinuria (PNH)

Covered when ALL of the following are met

PNH initial therapy: Flow cytometry confirming presence of PNH clones AND laboratory results, signs, and/or symptoms attributable to PNH (e.g., abdominal pain, anemia, dyspnea, fatigue, hemoglobinuria, thrombosis, kidney disease, pulmonary hypertension); for PiaSky initiation only: history of trial and failure, contraindication, or intolerance to Empaveli (pegcetacoplan), Fabhalta (iptacopan), or eculizumab/Ultomiris; patient is not receiving PiaSky in combination with a complement factor D inhibitor (e.g., Voydeya/danicopan); PiaSky or Ultomiris dosed per U.S. FDA labeling; patient is not receiving PiaSky or Ultomiris in combination with another complement C5 inhibitor, a complement C3 inhibitor (e.g., Empaveli), or a complement factor B inhibitor (e.g., Fabhalta); prescribed by, or in consultation with, a hematologist or oncologist; initial authorization for no more than 12 months.

PNH continuation: Patient previously treated with PiaSky or Ultomiris; documentation demonstrating a positive clinical response from baseline (e.g., increased/stable hemoglobin, reduced transfusions, improvement in hemolysis, decreased LDH, increased reticulocyte count); PiaSky or Ultomiris dosed per U.S. FDA labeling; patient is not receiving PiaSky or Ultomiris in combination with another complement C5 inhibitor, a complement C3 inhibitor, or a complement factor B inhibitor; for PiaSky, patient is not receiving PiaSky in combination with a complement factor D inhibitor; prescribed by, or in consultation with, a hematologist or oncologist; reauthorization for no more than 12 months.

inv-04: Generalized Myasthenia Gravis (gMG)

Covered when ALL of the following are met

gMG initial therapy: Medical records confirming: no prior failure of Ultomiris; diagnosis of generalized myasthenia gravis; positive anti‑AChR antibody serology; MGFA clinical classification class II–IV at initiation; MG‑ADL total score ≥ 6 at initiation; AND one of the following: history of failure of ≥2 immunosuppressive agents over ≥12 months OR history of failure of ≥1 immunosuppressive therapy plus ≥4 courses of plasmapheresis/IVIG over ≥12 months without symptom control; Ultomiris initiated and titrated per U.S. FDA labeling for gMG; patient is not receiving Ultomiris in combination with B‑cell depletion therapy (e.g., Uplizna), a different complement C5 inhibitor (e.g., Bkemv, Epysqli, PiaSky, Soliris, Ultomiris, Zilbrysq), an FcRN blocker (e.g., Vyvgart, Vyvgart Hytrulo, Rystiggo), or an immune globulin (e.g., Hizentra, Privigen, Gammagard); prescribed by, or in consultation with, a neurologist; initial authorization for no more than 12 months.MG-ADL ≥ 6

gMG continuation: Patient has previously been treated with Ultomiris; submission of medical records demonstrating ≥2‑point improvement in MG‑ADL from pre‑treatment baseline and reduction in signs and symptoms of myasthenia gravis; maintenance, reduction, or discontinuation of baseline immunosuppressive therapy (add‑on or dose escalation or rescue therapy from baseline while on eculizumab/Ultomiris is considered treatment failure); Ultomiris dosed per U.S. FDA labeling; patient is not receiving Ultomiris in combination with prohibited therapies (B‑cell depletion, other C5 inhibitors, FcRN blockers, or immune globulin); prescribed by, or in consultation with, a neurologist; reauthorization for no more than 12 months.

inv-05: Neuromyelitis Optica Spectrum Disorder (NMOSD)

Covered when ALL of the following are met

NMOSD initial therapy: Diagnosis of NMOSD by a neurologist with qualifying past history (optic neuritis, acute myelitis, area postrema syndrome, acute brainstem syndrome, symptomatic narcolepsy/diencephalic syndrome, or symptomatic cerebral syndrome); positive AQP4‑IgG serology; other diagnoses (e.g., multiple sclerosis) ruled out; no prior failure of Ultomiris; history of failure, contraindication, or intolerance to rituximab therapy; Ultomiris initiated and titrated per U.S. FDA dosing for NMOSD; prescribed by, or in consultation with, a neurologist; patient is not receiving Ultomiris in combination with disease‑modifying therapies for MS, anti‑IL6 therapy, or B‑cell depletion therapies; initial authorization for no more than 12 months.AQP4 antibody positive

NMOSD continuation: Patient has previously been treated with Ultomiris; documentation of positive clinical response from baseline as shown by reduction in number and/or severity of relapses or signs and symptoms AND maintenance, reduction, or discontinuation of baseline immunosuppressive therapy prior to starting Ultomiris (add‑on or escalation considered treatment failure); Ultomiris dosed per U.S. FDA labeling; prescribed by, or in consultation with, a neurologist; patient is not receiving Ultomiris in combination with prohibited therapies; reauthorization for no more than 12 months.

inv-06: aHUS (Initial therapy)

Covered when ALL of the following are met for aHUS:

aHUS initial therapy criteria: 1) Diagnosis of atypical hemolytic uremic syndrome; 2) Complement inhibitor–naïve adult meeting trial diagnostic thresholds (platelet count ≤ 150 × 10^9/L, evidence of hemolysis such as elevated LDH, and serum creatinine above the upper limit of normal or requiring dialysis); 3) Clinical intent to treat with ravulizumab using weight‑based dosing and monitoring per study/prescribing information; 4) Documentation of meningococcal vaccination or planned prophylactic antibiotics if urgent treatment;see node text

Complete TMA Response criteria defined in document

inv-07: PNH (Initial therapy)

Covered when ALL of the following are met for PNH:

PNH criteria (complement inhibitor–naïve): 1) Diagnosis of paroxysmal nocturnal hemoglobinuria; 2) Evidence of active hemolysis (LDH ≥ 1.5 × ULN) and at least one PNH‑associated symptom; 3) For treatment‑naïve patients, weight‑based ravulizumab or crovalimab dosing consistent with clinical trials; 4) Documentation of meningococcal vaccination prior to or at initiation or documentation of prophylactic antibiotics until 2 weeks after vaccination;LDH ≥ 1.5 × ULN

Trials required vaccination or prophylactic antibiotics

inv-08: Generalized Myasthenia Gravis (gMG)

Covered when ALL of the following are met for generalized myasthenia gravis (gMG):

gMG criteria: 1) Diagnosis of generalized myasthenia gravis with anti‑AChR antibody positivity; 2) MG‑ADL score ≥ 6 and MGFA class II–IV at screening; 3) Adult patient (≥18 years); 4) Vaccination against Neisseria meningitidis prior to initiation; 5) Weight‑based dosing per prescribing information;MG‑ADL ≥ 6

CHAMPION MG trial eligibility

inv-09: Neuromyelitis Optica Spectrum Disorder (NMOSD)

Covered when ALL of the following are met for NMOSD:

NMOSD criteria: 1) Diagnosis of neuromyelitis optica spectrum disorder with anti‑AQP4 antibody positive status; 2) Adult patient; 3) Weight‑based ravulizumab dosing and monitoring as per study/prescribing information; 4) Vaccination per ACIP and REMS enrollment;AQP4 antibody positive

CHAMPION‑NMOSD study criteria

inv-10: Ultomiris: Generalized Myasthenia Gravis — revised exclusions

Revised coverage criteria highlights

Generalized Myasthenia Gravis (AChR antibody positive): Coverage revised to require that the patient is not receiving Ultomiris in combination with an immune globulin (e.g., Hizentra, Privigen, Gammagard) for treatment of the same indication and is not receiving Ultomiris in combination with a different complement inhibitor (explicit drugs listed).

Full detailed criteria (e.g., prior therapies, diagnostic confirmation) are in other parts of the policy not included in this excerpt.

inv-11: Ultomiris: NMOSD initial therapy — removal of relapse-count requirement

Neuromyelitis Optica Spectrum Disorder (NMOSD) — Initial Therapy

NMOSD initial therapy: Removed previous requirement for documented history of either at least two relapses in the prior 12 months or three relapses in the prior 24 months (with one within the prior 12 months) as a criterion to initiate Ultomiris.

Other NMOSD coverage criteria remain in the policy but are not present in this excerpt.

PiaSky (crovalimab) and Ultomiris (ravulizumab) are specifically identified in the policy as unproven and not medically necessary for the treatment of Shiga toxin E. coli–related hemolytic uremic syndrome (STEC-HUS).

The policy notes under FDA Limitations of Use that Ultomiris is not indicated for the treatment of patients with Shiga toxin E. coli–related hemolytic uremic syndrome (STEC-HUS).

An operational exclusion has been added: patients receiving Ultomiris in combination with an immune globulin (examples given include Hizentra, Privigen, Gammagard) for the same indication are specifically excluded from receiving Ultomiris under this policy.

The policy states that the use of PiaSky and Ultomiris for treatment of Shiga toxin E. coli–related HUS (STEC-HUS) is considered unproven and not medically necessary, and the FDA section similarly notes that Ultomiris is not indicated for STEC-HUS.

Aside from the explicitly stated exclusions (for example, the new exclusion for concomitant use of Ultomiris with an immune globulin and the revised prohibition on combining Ultomiris with other specified complement inhibitors), the excerpt does not introduce additional general “not medically necessary” statements beyond the STEC‑HUS determination and the noted change to NMOSD initial-therapy relapse-count requirements.

Billing, Procedure, and Diagnostic Codes

Procedure/administration codesHCPCS

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

Diagnosis codesICD-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

Covered HCPCS/Q codes (listed for reference)HCPCS

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

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.

Applicable HCPCS Codes AddedHCPCSCovered

Q5151	HCPCS code added (policy-specific billing code)
Q5152	HCPCS code added (policy-specific billing code)

Applicable HCPCS Codes RemovedHCPCSNot Covered

C9399	Previously listed HCPCS code removed
J3490	Previously listed HCPCS code removed
J3590	Previously listed HCPCS code removed

inv-23: LDH level for PNH enrollment in trials

LDH thresholdLDH ≥ 1.5 × upper limit of normal (ULN)

ContextUsed as an enrollment eligibility threshold in PNH clinical trials comparing ravulizumab and eculizumab.

Associated requirementPresence of at least one PNH-associated symptom in trial-eligible patients.

inv-24: Platelet count for aHUS trial inclusion

Platelet count thresholdPlatelet count ≤ 150 × 10^9/L

Authorization, Documentation, and Provider Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for Ultomiris (ravulizumab), PiaSky (crovalimab), and listed eculizumab biosimilars. Typical initial and reauthorization approvals are for up to 12 months. Submit a completed prior authorization request with supporting medical records (chart notes, laboratory results, flow cytometry, MG‑ADL scores, prior therapy history) to demonstrate criteria are met. Failure to document exclusion of STEC‑HUS and TTP (e.g., ADAMTS13 deficiency) when requesting Ultomiris for aHUS may result in denial.

Prior authorization required — initial and reauthorization up to 12 months.
Include documentation ruling out STEC‑HUS and TTP for aHUS requests.
Submit medical records: chart notes, labs, diagnostic testing (e.g., flow cytometry for PNH), MG‑ADL scores, and prior therapy history.

Documentation Required

REMS Enrollment and Vaccination Requirements

When requesting coverage, include documentation of meningococcal vaccination per ACIP or, if vaccination cannot be completed prior to urgent initiation, document administration of vaccine(s) as soon as possible and provision of prophylactic antibiotics until vaccination is effective. Enrollment of the prescriber (and patient when required) in the applicable REMS program (Ultomiris or PiaSky) must be documented; failure to enroll or to follow REMS monitoring and vaccination requirements may prevent appropriate use and pose patient safety risks.

Background and Scope

Ravulizumab (Ultomiris) and crovalimab (PiaSky) are monoclonal antibodies that bind to complement protein C5 to inhibit its cleavage and thereby prevent formation of the terminal complement complex (membrane attack complex), which reduces terminal complement–mediated intravascular hemolysis and related tissue injury.

Key Terms and Definitions

inv-38: Mechanism of action for ravulizumab and crovalimab

Mechanism summaryTerminal complement complex inhibition

Primary actionMonoclonal antibodies bind complement protein C5 to inhibit its cleavage to C5a and C5b, preventing generation of C5b-9 (terminal complement complex).

Clinical effectPrevents terminal complement–mediated intravascular hemolysis and downstream endothelial/platelet injury in complement‑mediated diseases.

inv-39: Terminal complement inhibition

Molecular targetBinds to complement protein C5 to inhibit its cleavage to C5a and C5b.

Downstream effectPrevents formation of the membrane attack complex (C5b-9/MAC), thereby inhibiting terminal complement activity.

OpenPayer

Complement Inhibitors (for Ohio Only)

Coverage and Medical Necessity Criteria

Billing, Procedure, and Diagnostic Codes

Authorization, Documentation, and Provider Requirements

Background and Scope

Key Terms and Definitions