CurrentUnitedHealthcarePolicy 2026D0049AD

Complement Inhibitors Policy 2026D0049AD

UnitedHealthcare medical benefit drug policy defining coverage, preferred products, diagnosis-specific medical necessity criteria, continuation criteria, and applicable HCPCS/J-codes and ICD-10 diagnosis codes for complement inhibitor products (Bkemv, Epysqli, PiaSky, Soliris, Ultomiris). Applies to commercial and medical benefit contexts and includes background and clinical evidence summaries.

Policy Summary

PayerUnitedHealthcare

PolicyComplement Inhibitors Policy 2026D0049AD

Policy CodePolicy 2026D0049AD

Change TypePreferred-product designation; coverage criteria revised

Effective DateJan 1, 2026

Next Review Date

Key ActionPrior authorization required; submit medical records documenting diagnosis-specific criteria, trial/failure or intolerance details, dosing per FDA label, and specialist consultation as specified.

POLICY UPDATE CHANGES

Added language designating Bkemv and Epysqli as the preferred eculizumab products and defined coverage/switching requirements and Soliris Preferred Product Criteria.

Removed reference link to the Medical Benefit Drug Policy 'Review at Launch for New to Market Medications' for Bkemv and Epysqli.

Archived previous policy version 2025D0049AC.

Updated CMS section to reflect most current information.

5Drugs referenced

4Primary covered indications

5HCPCS/Q codes listed

1Material policy change

≥14 weeksRequired trial duration before Soliris

Coverage Summary

Coverage stance: covered_with_criteria. Scope: this UnitedHealthcare Medical Benefit Drug Policy applies to complement C5 inhibitors Bkemv, Epysqli, PiaSky, Soliris, and Ultomiris and defines diagnosis-specific medical necessity criteria, continuation requirements, and relevant HCPCS/J and Q codes for commercial/medical benefit contexts.

Covered-with-criteria status and preferred-product policy: the policy designates Bkemv (eculizumab-aeeb) and Epysqli (eculizumab-aagh) as the preferred eculizumab products for Medical Necessity Plans; Soliris (eculizumab) coverage is allowed only when the Preferred Product Criteria are met. Members already on Soliris in Medical Necessity Plans must switch to Bkemv or Epysqli to continue coverage unless they meet the Soliris Preferred Product Criteria (e.g., documented ≥ 14-week trial of preferred agents with inadequate response, documented intolerance/contraindication, or other specified exception).

Plan-type distinctions: for Medical Necessity Plans preferred-product criteria and switching requirements apply; for Non-Medical Necessity Plans any complement inhibitor may be approved contingent on the Diagnosis-Specific Criteria. Medicare/Medicare Advantage note: preferred therapy criteria do not apply to Medicare Advantage members per the CMS section.

Key thresholds and quick facts

Effective dateJanuary 1, 2026

MG-ADL threshold (initiation)>= 6 at initiation

MG-ADL threshold (continuation)>= 2-point improvement from pre-treatment baseline for reauthorization

MGFA Clinical ClassificationClass II, III, or IV at initiation

aHUS initial lab eligibility (trial inclusion)Platelet count <= 150 x10^9/L plus evidence of hemolysis and serum creatinine above ULN

PNH LDH inclusion (trial)LDH >= 1.5 x ULN plus at least 1 PNH symptom

Required trial duration of preferred eculizumab products before Soliris>= 14 weeks of Bkemv and Epysqli trial documented

Source of thresholdsUnitedHealthcare Complement Inhibitors policy (Policy No. 2026D0049AD)

Initial Therapy Criteria (by indication)

Initial Therapy

Diagnosis-specific medical necessity criteria for initial and continuation therapy with complement inhibitors by indication.

Atypical Hemolytic Uremic Syndrome (aHUS) - Initial and Continuation Therapy

Initial Therapy
- Documentation supporting the diagnosis of aHUS by ruling out both Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS) and thrombotic thrombocytopenia purpura (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.

Preferred Product Criteria and Switching Rules

The Preferred Product Criteria (Policy History 01/01/2026) distinguish Medical Necessity Plans versus Non-Medical Necessity Plans and set explicit requirements for continuing or initiating Soliris. For Medical Necessity Plans Bkemv and Epysqli are preferred; Soliris is medically necessary only when the Preferred Product Criteria are met.

Soliris switching/approval requirements: to qualify for Soliris coverage a member must meet one of the following pathways: (1) documentation of a trial of at least 14 weeks of both Bkemv and Epysqli with minimal clinical response and a physician attestation that Soliris is expected to produce superior clinical benefit; or (2) documentation of intolerance, contraindication, or an adverse event to both Bkemv and Epysqli with physician attestation that the same intolerance/adverse event would not be expected with Soliris. Additionally, the patient must not have had loss of a favorable response after established maintenance therapy with an eculizumab product.

For Non-Medical Necessity Plans any complement inhibitor may be approved when the Diagnosis-Specific Criteria are met; the preferred-product switching mandate does not apply.

Unproven Indications and Exclusions

Provider Actions and Authorization Requirements

Prior Authorization

Prior authorization required with documentation

Submit prior authorization with supporting medical records documenting the diagnosis-specific criteria required by the policy (e.g., flow cytometry for PNH; AQP4-IgG for NMOSD; anti-AChR for gMG; exclusion of STEC-HUS and ADAMTS13 deficiency for aHUS), trials/failures/intolerances when required, dosing per US FDA label, and prescriber specialty consultation as specified.

J1299
J1303
J1307
Q5151
Q5152

Prior Authorization

Preferred-product and switching requirements

Applicable Codes

Drug HCPCS/J and Q Codesmixed

J1299	Injection, eculizumab, 2 mg
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

Referenced ICD-10 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

Drugs discussed (by proprietary name and INN suffix)mixed

Bkemv	eculizumab-aeeb (Amgen) - preferred eculizumab product per policy (2026 change)
Epysqli	eculizumab-aagh (Samsung Bioepis) - preferred eculizumab product per policy (2026 change)
Soliris	eculizumab (Alexion) - non-preferred; coverage allowed only if Preferred Product Criteria met
Ultomiris	ravulizumab-cwvz (Alexion) - indicated for multiple FDA-approved indications
PiaSky	crovalimab-akkz (Genentech) - indicated for PNH ≥13 years & ≥40 kg

Safety, REMS and FDA Indications

FDA indications and limitations (informational):

Bkemv (eculizumab-aeeb): indicated for PNH (reduce hemolysis); aHUS in patients ≥ 1 month (inhibit complement-mediated TMA); and gMG in adult anti-AChR antibody positive patients. Limitation: not indicated for STEC-HUS.

Epysqli (eculizumab-aagh): indicated for PNH; aHUS in patients ≥ 1 month; and gMG in adult anti-AChR antibody positive patients. Limitation: not indicated for STEC-HUS.

PiaSky (crovalimab-akkz): indicated for PNH in adults and pediatric patients ≥ 13 years with body weight ≥ 40 kg. Note: increases risk of serious Neisseria meningitidis infections.

Soliris (eculizumab): indicated for PNH; aHUS; gMG in patients ≥ 6 years who are anti-AChR antibody positive; and NMOSD in adult AQP4 antibody positive patients. Limitation: not indicated for STEC-HUS.

Ultomiris (ravulizumab-cwvz): indicated for PNH and aHUS in patients ≥ 1 month; gMG in adult anti-AChR antibody positive patients; and NMOSD in adult AQP4 antibody positive patients. Limitation: not indicated for STEC-HUS.

Vaccination and REMS operational guidance: vaccinate patients receiving complement inhibitors for meningococcal disease per the most current ACIP recommendations and revaccinate as indicated by ACIP considering treatment duration. For Soliris and Ultomiris, immunize patients without prior meningococcal vaccination at least 2 weeks before the first dose; if urgent therapy is required in an unvaccinated patient, administer meningococcal vaccine(s) as soon as possible and monitor closely.

PiaSky-specific infection guidance: complete or update meningococcal vaccination at least 2 weeks prior to the first PiaSky dose unless the risks of delaying PiaSky outweigh the infection risk; patients remain at increased risk for invasive Neisseria meningitidis disease even after vaccination and should be monitored for early signs/symptoms and evaluated immediately if infection is suspected.

Clinical Evidence Highlights

53.6%aHUS complete TMA response (ravulizumab) at 26 weeks

NoninferiorPNH: ravulizumab noninferior to eculizumab for transfusion avoidance & LDH normalization

-3.1 vs -1.4gMG CHAMPION MG: MG-ADL improvement at 26 weeks (ravulizumab vs placebo), p<0.001

0 vs 3%CHAMPION‑NMOSD (ravulizumab) 0 adjudicated relapses (n=58) vs PREVENT eculizumab placebo 3% relapses; PREVENT overall: eculizumab 3% vs placebo 43% (HR 0.06, p<0.001)

Clinical evidence context: eculizumab, ravulizumab, and crovalimab are monoclonal antibodies that bind complement protein C5 to inhibit terminal complement activation and are approved across PNH, aHUS, gMG, and NMOSD with supportive trial evidence.

Key trials linked to indications: ravulizumab demonstrated a 53.6% complete TMA response in a 26-week aHUS study and noninferiority to eculizumab in PNH studies (transfusion avoidance and LDH normalization). Ravulizumab (CHAMPION-MG) showed significant improvement in MG-ADL at 26 weeks versus placebo, and ravulizumab (CHAMPION-NMOSD) had zero adjudicated relapses versus external PREVENT placebo (relapse risk reduction 98.6%). Eculizumab demonstrated relapse reduction in PREVENT for NMOSD (3% vs 43% placebo). These trials underpin the labeled indications summarized in the policy.

Definitions

Term	Definition
{"text":"Complement C5 inhibitor","status":""}:{"text":"Therapies that bind complement protein C5 (e.g., eculizumab, ravulizumab, crovalimab) to inhibit terminal complement activation.","status":""}
{"text":"MG-ADL","status":""}:{"text":"Myasthenia Gravis Activities of Daily Living scale; used to assess symptom burden in gMG (thresholds specified in policy).","status":""}
{"text":"Medical Necessity Plans","status":""}:{"text":"UnitedHealthcare plan type where preferred-product criteria apply and switching requirements to preferred agents may be enforced.","status":""}
{"text":"Non-Medical Necessity Plans","status":""}:{"text":"UnitedHealthcare plan type where any complement inhibitor may be approved contingent on Diagnosis-Specific Criteria without preferred-product switching mandate.","status":""}

Revision History

2026-01-01revisedLatest

Designated Bkemv (eculizumab-aeeb) and Epysqli (eculizumab-aagh) as the preferred eculizumab products for Medical Necessity Plans; added Preferred Product Criteria requiring members on Soliris to switch to Bkemv or Epysqli to continue coverage unless they meet specified exceptions (trial of ≥14 weeks of Bkemv and Epysqli with minimal response plus physician attestation, documented intolerance/contraindication with physician attestation, or prior loss of favorable response). Marked as the material policy change.

2026-01-01removed

Removed reference link to the Medical Benefit Drug Policy 'Review at Launch for New to Market Medications' for Bkemv and Epysqli.

2026-01-01

Policy Summary

PayerUnitedHealthcare

PolicyComplement Inhibitors Policy 2026D0049AD

Policy CodePolicy 2026D0049AD

Change TypePreferred-product designation; coverage criteria revised

Effective DateJan 1, 2026

Next Review Date

On This Page

The requested product is dosed according to the US FDA labeled dosing for aHUS.

Dose and schedule must match the current FDA label for the specific product requested.

Prescribed by or in consultation with a hematologist or nephrologist.

Initial authorization will be for no more than 12 months.

Continuation of Therapy

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).
The requested product is dosed according to the US FDA labeled dosing for aHUS.
Dose and schedule must match the current FDA label for the specific product requested.
Prescribed by, or in consultation with, a hematologist or nephrologist.
Reauthorization will be for no more than 12 months.

Paroxysmal Nocturnal Hemoglobinuria (PNH) - Initial and Continuation Therapy including PiaSky-specific branch

Initial Therapy
- Documentation supporting the diagnosis of PNH that includes flow cytometry analysis confirming presence of PNH clones.
- Laboratory results, signs, and/or symptoms attributed to PNH (e.g., abdominal pain, anemia, dyspnea, extreme fatigue, smooth muscle dystonia, unexplained/unusual thrombosis, hemolysis/hemoglobinuria, kidney disease, pulmonary hypertension).
- The requested product is dosed according to the US FDA labeled dosing for PNH.
  Dose and schedule must match the current FDA label for the specific product requested.
- Patient is not receiving the requested product in combination with any of the following for treatment of the same indication: a different complement C5 inhibitor (Bkemv, Epysqli, PiaSky, Soliris, or Ultomiris), a complement C3 inhibitor (e.g., Empaveli/pegcetacoplan), or a complement factor B inhibitor (e.g., Fabhalta/iptacopan).
- PiaSky-specific authorization requirements
  - History of trial and failure, contraindication, or intolerance to one of the following: a complement C5 inhibitor (Bkemv, Epysqli, Soliris, or Ultomiris); Empaveli (pegcetacoplan); or Fabhalta (iptacopan).
  - Physician attests that in their clinical opinion the same intolerance, contraindication, or adverse event would not be expected to occur with Soliris.
- Prescribed by or in consultation with a hematologist or oncologist.
- Initial authorization will be for no more than 12 months.
Continuation of Therapy
- Patient has previously been treated with the requested product.
- Documentation demonstrating a positive clinical response from baseline (e.g., increased or stabilization of hemoglobin levels, reduction in transfusions, improvement in hemolysis, decrease in LDH, increased reticulocyte count).
- The requested product is dosed according to the US FDA labeled dosing for PNH.
  Dose and schedule must match the current FDA label for the specific product requested.
- Patient is not receiving the requested product in combination with any of the following for treatment of the same indication: a different complement C5 inhibitor (Bkemv, Epysqli, PiaSky, Soliris, or Ultomiris), a complement C3 inhibitor (e.g., Empaveli), or a complement factor B inhibitor (e.g., Fabhalta).
- PiaSky continuation-specific

Neuromyelitis Optica Spectrum Disorder (NMOSD) - Initial and Continuation Therapy

Initial Therapy
- Diagnosis of NMOSD by a neurologist confirming past medical history of one of the following: optic neuritis; acute myelitis; area postrema syndrome (episode of otherwise unexplained hiccups or nausea and vomiting); acute brainstem syndrome; symptomatic narcolepsy or acute diencephalic clinical syndrome with NMOSD-typical diencephalic MRI lesions; or symptomatic cerebral syndrome with NMOSD-typical brain lesions.
- Positive serologic test for anti-aquaporin-4 immunoglobulin G (AQP4-IgG)/NMO-IgG antibodies.
- Diagnosis of multiple sclerosis or other diagnoses have been ruled out.
- Patient has not failed a previous course of a complement C5 inhibitor therapy.
  If prior C5 inhibitor therapy failed, include documentation and clinical rationale for switching.
- The requested product is dosed according to the US FDA labeled dosing for NMOSD.
  Dose and schedule must match the current FDA label for the specific product requested.
- Prescribed by, or in consultation with, a neurologist.
- Initial authorization will be for no more than 12 months.
Continuation of Therapy
- Patient has previously been treated with the requested product.
- Documentation demonstrating clinical benefit such as reduction in relapse frequency or severity compared to baseline, stabilization or improvement in neurological function, or other objective evidence of disease control.
- The requested product is dosed according to the US FDA labeled dosing for NMOSD.
  Dose and schedule must match the current FDA label for the specific product requested.
- Prescribed by, or in consultation with, a neurologist.
- Reauthorization will be for no more than 12 months.

For Medical Necessity Plans, Bkemv and Epysqli are designated as the preferred eculizumab products. Coverage for Soliris is contingent on meeting the Preferred Product Criteria. Members already receiving Soliris must change therapy to Bkemv or Epijkstra to continue coverage unless they meet the Soliris Preferred Product Criteria (e.g., documentation of a trial of at least 14 weeks of Bkemv and Epiyini with minimal response and physician attestation of expected superior response with Soliris, or documented intolerance/contraindication to preferred products).

Denial Risk

Combination therapy exclusions

Claims may be denied if the requested product is used in combination with excluded agents for the same indication. Specified combinations that will trigger denial include use with a different complement C5 inhibitor, a complement C3 inhibitor, or a complement factor B inhibitor (and for PiaSky, combination with a complement factor D inhibitor is restricted).

Different complement C5 inhibitor (e.g., Bkemv, Epysqli, Soliris, Ultomiris, PiaSky)
Complement C3 inhibitor (e.g., Empaveli/pegcetacoplan)
Complement factor B inhibitor (e.g., Fabhalta/iptacopan)
For PiaSky: not in combination with a complement factor D inhibitor (e.g., Voydeya/danicopan)

Documentation Required

Specialist prescribing requirement

Requested products must be prescribed by, or in consultation with, the specialist(s) specified by indication: hematologist or nephrologist for aHUS; hematologist or oncologist for PNH; neurologist for gMG and NMOSD. Ensure documentation of the specialist prescription or consult in the medical record.

Billing Rule

Dosing per FDA label

Dosing must follow the US FDA–labeled regimen for the requested indication. Initial authorizations and reauthorizations are limited to no more than 12 months.

Authorization duration: initial ≤ 12 months
Reauthorization ≤ 12 months

Documentation Required

Physician attestation required for Soliris approval

When requesting Soliris based on inadequate response or intolerance to preferred eculizumab products, the physician must document the trial details (including a trial of at least 14 weeks when applicable) and provide a signed attestation that Soliris is expected to provide superior clinical response or that the same intolerance/contraindication would not be expected to recur with Soliris.

Document trial duration and clinical response to Bkemv/Epysqli (≥14 weeks when required)
Document intolerance/contraindication when applicable
Physician attestation of expected superior response or non-recurrence of intolerance

Documentation Required

REMS enrollment

Prescribers must enroll in the applicable REMS program prior to prescribing these agents. Bkemv, Epysqli, PiaSky, Soliris, and Ultomiris are available only through restricted REMS programs and prescriber enrollment is required.

Enroll in REMS for Bkemv, Epysqli, PiaSky, Soliris, Ultomiris before prescribing

Documentation Required

Meningococcal vaccination timing

Meningococcal vaccination must follow current ACIP recommendations. For Soliris and Ultomiris, immunize unvaccinated patients at least 2 weeks prior to first dose; for PiaSky complete or update meningococcal vaccination at least 2 weeks before first dose unless risks of delaying therapy outweigh infection risk. If urgent therapy is indicated in an unvaccinated patient, administer meningococcal vaccine(s) as soon as possible and closely monitor for infection.

Vaccinate per ACIP and revaccinate per ACIP considering therapy duration
If urgent therapy needed, give vaccine ASAP and monitor closely

Denial Risk

Noncompliance with preferred-product policy

For members in Medical Necessity Plans, failure to meet the Preferred Product Criteria may result in claim denial or requirement to switch to preferred agents (Bkemv or Epysqli) unless an exception is documented per policy.

REMS requirements: Bkemv, Epysqli, PiaSky, Soliris, and Ultomiris are available only through restricted REMS programs; prescribers must enroll in the respective REMS program prior to prescribing.

Archived previous policy version 2025D0049AC.

2026-01-01updated

Updated CMS section to reflect the most current information, including note that preferred therapy criteria is not applicable for Medicare Advantage members.

Patient is not receiving PiaSky in combination with a complement factor D inhibitor (e.g., Voydeya/danicopan).

Prescribed by, or in consultation with, a hematologist or oncologist.

Reauthorization will be for no more than 12 months.