CurrentUnitedHealthcarePolicy IEXD0049.18

Complement Inhibitors

Medical benefit drug policy governing coverage criteria, initial and continuation authorization requirements, and applicable procedure/diagnosis codes for complement inhibitor products (Bkemv, Epysqli, PiaSky, Soliris, Ultomiris) for indications including aHUS, PNH, gMG (anti-AChR+), and NMOSD (AQP4+).

Policy Summary

PayerUnitedHealthcare

PolicyComplement Inhibitors

Policy CodePolicy IEXD0049.18

Change TypeCoverage criteria revised; new biosimilars added; REMS & vaccination updates

Effective DateSep 1, 2025

Next Review Date

Key ActionProviders must submit medical records confirming diagnosis, prior therapy trials/failures, vaccination and REMS enrollment per indication-specific criteria and obtain prior authorization.

POLICY UPDATE CHANGES

Added Bkemv (eculizumab-aeeb) and Epysqli (eculizumab-aagh) to the list of applicable complement inhibitor drug products.

Revised coverage criteria language for PNH, gMG, and NMOSD to reference 'complement C5 inhibitor therapy' generically and adjusted combination therapy prohibitions.

Added HCPCS codes Q5151 and Q5152.

Updated FDA and References sections to reflect current information.

Added statements regarding meningococcal vaccination timing, revaccination, monitoring, and REMS enrollment requirements for listed products.

4Complement inhibitor products listed (medical benefit)

4Primary covered indications (aHUS, PNH, gMG, NMOSD)

Products unproven for STEC-HUS

12Authorization duration (months max per approval)

5Complement inhibitor products mentioned (incl. biosimilars)

Coverage Summary

This medical benefit drug policy (effective September 1, 2025) governs coverage and medical necessity criteria for complement inhibitors provided under the medical benefit: Bkemv (eculizumab-aeeb), Epysqli (eculizumab-aagh), PiaSky (crovalimab-akkz), Soliris (eculizumab), and Ultomiris (ravulizumab-cwvz) for the indications atypical hemolytic uremic syndrome (aHUS), paroxysmal nocturnal hemoglobinuria (PNH), generalized myasthenia gravis (gMG) anti-AChR antibody positive, and neuromyelitis optica spectrum disorder (NMOSD) AQP4-IgG positive when the indication-specific criteria are met.

Zilbrysq (zilucoplan) is a self-administered product obtained under the pharmacy benefit and is excluded from this medical benefit policy.

Coverage stance: these listed medical-benefit complement inhibitors are considered covered with criteria; initial and continuation authorizations are available per the policy criteria and are limited to up to 12 months for each approval period (see indication-specific initial and reauthorization criteria).

Quick facts and thresholds

MG-ADL initiation threshold>= 6

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

Authorization duration limitInitial and reauthorization approvals limited to no more than 12 months (i.e., up to 12 months)

Review at Launch noteBkemv and Epysqli added to 'Review at Launch' — some members may not be eligible for coverage at this time

REMS/ACIP noteREMS enrollment required for Bkemv/Epysqli/Bkemv, and meningococcal vaccination per ACIP guidance (vaccinate >=2 weeks before first dose or as soon as possible if urgent) — prescribers must enroll in REMS

Initial Therapy Criteria

Atypical Hemolytic Uremic Syndrome (aHUS) - Initial Therapy

Covered 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, etc.)
Patient is treatment naïve with the requested product
Requested product is dosed according to the US FDA labeled dosing for aHUS

Continuation Therapy Criteria

Atypical Hemolytic Uremic Syndrome (aHUS) - Continuation of Therapy

Covered when ALL of the following are met:

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 US FDA labeled dosing for aHUS

Prescribed by, or in consultation with, a hematologist or nephrologist

Reauthorization will be for no more than 12 months

Unproven / Exclusions

STEC-HUS

Bkemv, Epysqli, PiaSky, Soliris, and Ultomiris are unproven and not medically necessary for treatment of Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS)

Use of the listed complement inhibitors (Bkemv, Epysqli, PiaSky, Soliris, Ultomiris) for Shiga toxin E. coli–related hemolytic uremic syndrome (STEC-HUS) is considered unproven and not medically necessary and may be denied.

This denial risk is called out in the provider actions and documentation requirements; providers should be aware that requests for these products for STEC-HUS may be subject to denial if criteria for a covered indication are not met.

Applicable Codes

HCPCS / J-codesHCPCS

J1299	Injection, eculizumab, 2 mg
J1303	Injection, ravulizumab-cwvz, 10 mg
J1307	Injection, crovalimab-akkz, 10 mg

HCPCS / Q-codes (biosimilars)HCPCS

Q5151	Injection, eculizumab-aagh (Epysqli), biosimilar, 2 mg
Q5152	Injection, eculizumab-aeeb (Bkemv), biosimilar, 2 mg

ICD-10 Diagnosis Codes (referenced)ICD-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
Q5152

Provider Actions & Requirements

Prior Authorization

Prior Authorization Required; Authorization Durations

Prior authorization is required for all complement inhibitor agents. Initial authorizations will be issued for up to 12 months; reauthorizations (continuation of therapy) may be granted in increments up to 12 months when continuation criteria are met and documentation of clinical benefit is provided.

Initial authorization duration: up to 12 months
Reauthorization/continuation: up to 12 months per approval period

Documentation Required

Diagnosis Confirmation and Prior Treatment History

Provide documentation confirming the diagnosis and prior treatment history. Include relevant diagnostic testing to support the requested indication.

For PNH: flow cytometry confirming presence of PNH clones

Clinical Evidence & Metrics

53.6%Ultomiris (ravulizumab) aHUS: Complete TMA Response (phase 3 single‑arm, 26‑week) — 53.6% achieved Complete TMA Response

NoninferiorUltomiris (ravulizumab) in PNH: demonstrated noninferiority to eculizumab on coprimary endpoints (transfusion avoidance; LDH normalization) in phase 3 studies

0 vs 20Ravulizumab (CHAMPION‑NMOSD): no adjudicated relapses on ravulizumab (n=58) vs 20 adjudicated relapses in external placebo comparator (PREVENT) — relapse risk reduction 98.6%

PI/REMSContext: See Soliris (eculizumab) PI (Feb 2025) and Ultomiris PI (Mar 2024); Bkemv/Epysqli/PiaSky/Soliris/Ultomiris available only via REMS per prescribing information

Selected evidence highlights: prescribing information dates are cited in the policy references (Soliris prescribing information: February 2025; Ultomiris prescribing information: March 2024).

Clinical evidence summarized in the policy supports the covered indications: for aHUS, ravulizumab demonstrated a Complete TMA Response rate of 53.6% in a phase 3 single-arm study and eculizumab showed improvements in renal and hematologic endpoints in phase 2 trials; for PNH, ravulizumab was noninferior to eculizumab on coprimary endpoints in phase 3 studies; for NMOSD, ravulizumab prevented adjudicated relapses in CHAMPION‑NMOSD versus an external comparator; for gMG, randomized trials of ravulizumab and eculizumab provide the primary clinical trial evidence summarized in the policy.

Background

Background: complement inhibitors in this policy (eculizumab, ravulizumab, crovalimab and eculizumab biosimilars) are monoclonal antibody–based C5 complement inhibitors used to treat autoimmune and hematologic conditions including aHUS, PNH, gMG (anti‑AChR+), and NMOSD (AQP4+).

Zilbrysq (zilucoplan) is a self-administered complement inhibitor obtained under the pharmacy benefit and therefore is explicitly excluded from this medical benefit policy.

These products are available only through REMS programs due to infectious risk (e.g., meningococcal infections) and vaccination and REMS enrollment requirements are detailed in the policy.

Key definitions

Treatment naïve (definition)Patient has not previously received the requested complement inhibitor product

Positive clinical response (continuation)Indication-specific objective improvement as defined in continuation criteria (e.g., lab improvements, reduced interventions, symptom score improvements)

REMSRisk Evaluation and Mitigation Strategy — required FDA risk management program; listed products (Bkemv, Epysqli, PiaSky, Soliris, Ultomiris) are available only through REMS and prescribers must enroll

Revision History

2025-09-01policy_effective_dateLatest

Policy effective date 09/01/2025; modifications to clinical coverage criteria implemented.

2025-09-01added_drugsLatest

Added Bkemv (eculizumab-aeeb) and Epysqli (eculizumab-aagh) to the list of applicable complement inhibitor drug products and to the 'Review at Launch' program; some members may not be eligible for coverage pending Review at Launch determinations.

2025-09-01

Policy Summary

PayerUnitedHealthcare

PolicyComplement Inhibitors

Policy CodePolicy IEXD0049.18

Change TypeCoverage criteria revised; new biosimilars added; REMS & vaccination updates

Effective DateSep 1, 2025

Next Review Date

Key ActionProviders must submit medical records confirming diagnosis, prior therapy trials/failures, vaccination and REMS enrollment per indication-specific criteria and obtain prior authorization.

On This Page

Prescribed by or in consultation with a hematologist or nephrologist

Initial authorization will be for no more than 12 months

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 US FDA labeled dosing for aHUS
Prescribed by, or in consultation with, a hematologist or nephrologist
Reauthorization will be for no more than 12 months

STEC-HUS

Bkemv, Epysqli, PiaSky, Soliris, and Ultomiris are unproven and not medically necessary for treatment of Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS)

Paroxysmal Nocturnal Hemoglobinuria (PNH) - Initial Therapy

Covered when ALL of the following are met:

Documentation supporting the diagnosis of PNH that includes both flow cytometry analysis confirming presence of PNH clones and 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, etc.)

Requested product is dosed according to the US FDA labeled dosing for PNH

PiaSky-specific: For PiaSky authorization only, history of trial and failure, contraindication, or intolerance to one of: a complement C5 inhibitor (Bkemv, Epysqli, Soliris, Ultomiris), Empaveli (pegcetacoplan), or Fabhalta (iptacopan)

PiaSky-specific: For PiaSky authorization only, patient is not receiving PiaSky in combination with a complement factor D inhibitor (e.g., Voydeya/danicopan)

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; a complement C3 inhibitor (e.g., Empaveli/pegcetacoplan); or a complement factor B inhibitor (e.g., Fabhalta/iptacopan)

Prescribed by or in consultation with a hematologist or oncologist

Initial authorization will be for no more than 12 months

Generalized Myasthenia Gravis (gMG) - anti-AChR antibody positive - Initial Therapy

Covered when ALL of the following are met:

Submission of medical records confirming all of the following: 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 of class II, III, or IV at initiation of therapy; MG-ADL total score >= 6 at initiation of therapy

ONE of

History of failure of at least two immunosuppressive agents over the course of at least 12 months (e.g., azathioprine, corticosteroids, cyclosporine, methotrexate, mycophenolate)
OR: Failure of at least one immunosuppressive therapy; and Four or more courses of plasmapheresis/plasma exchanges and/or intravenous immune globulin over the course of at least 12 months without symptom control

Requested product is initiated and titrated according to the US FDA labeled dosing for gMG

Patient is not receiving the requested product in combination with any of the following for the same indication: a different complement C5 inhibitor or an FcRn blocker (e.g., Vyvgart, Vyvgart Hytrulo, Rystiggo)

Prescribed by or in consultation with a neurologist

Initial authorization will be for no more than 12 months

Neuromyelitis Optica Spectrum Disorder (NMOSD) - Initial Therapy

Covered when ALL of the following are met:

Diagnosis of NMOSD by a neurologist confirming: past medical history of an NMOSD-typical event (optic neuritis; acute myelitis; area postrema syndrome; acute brainstem syndrome; symptomatic narcolepsy/acute diencephalic syndrome with NMOSD-typical MRI lesions; symptomatic cerebral syndrome with NMOSD-typical brain lesions)

Positive serologic test for anti-aquaporin-4 (AQP4-IgG)/NMO-IgG antibodies; and diagnosis of multiple sclerosis or other diagnoses have been ruled out

Patient has not failed a previous course of a complement C5 inhibitor therapy for NMOSD (Bkemv, Epysqli, Soliris, Ultomiris)

ONE of

History of failure of, contraindication, or intolerance to rituximab therapy
History of at least two relapses during the previous 12 months prior to initiating the requested product
History of at least three relapses during the previous 24 months, with at least one relapse occurring within the past 12 months prior to initiating the requested product

Requested product is initiated and titrated according to the US FDA labeled dosing for NMOSD

Prescribed by, or in consultation with, a neurologist

Patient is not receiving the requested product in combination with disease modifying therapies FDA approved for MS; anti-IL6 therapy (e.g., Actemra, Enspryng); or B-cell depletion therapy (e.g., rituximab, Uplizna)

Initial authorization will be for no more than 12 months

Vaccination and infection monitoring requirements

Covered when ALL of the following are met:

Vaccinate for meningococcal disease according to the most current ACIP recommendations for patients with complement deficiencies

Revaccinate patients in accordance with ACIP recommendations, considering the duration of complement inhibitor therapy

Immunize patients without a history of meningococcal vaccination at least 2 weeks prior to receiving the first dose of Soliris or Ultomiris

If urgent therapy is indicated in an unvaccinated patient, administer meningococcal vaccine(s) as soon as possible

Closely monitor patients for early signs and symptoms of meningococcal infection and evaluate patients immediately if an infection is suspected

REMS enrollment requirement

Coverage/dispensing requires adherence to REMS program enrollment where applicable:

Prescribers must enroll in the REMS program for Bkemv, Epulluni, PiaSky, Soliris and Ultomiris as these products are available only through a restricted REMS program

Operational note: Enrollment/contact information: Bkemv REMS telephone 1-866-718-6927; Epysqli REMS telephone 1-866-318-0342; PiaSky REMS telephone 1-866-469-7599; Soliris/Ultomiris REMS telephone 1-888-765-4747; websites provided in policy

FDA Indications and Limitations of Use (soliris and ultomiris examples)

Approved indications and stated limitations as per FDA prescribing information:

Soliris (eculizumab) indications: treatment of PNH to reduce hemolysis

Soliris indications: treatment of atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy

Soliris indications: treatment of adult and pediatric patients >= 6 years with generalized Myasthenia Gravis (gMG) who are anti-AChR antibody positive

Soliris indications: treatment of NMOSD in adult patients who are anti-AQP4 antibody positive

Soliris limitation: not indicated for Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS)

Ultomiris (ravulizumab-cwvz) indications: treatment of adult and pediatric patients >= 1 month with PNH

Ultomiris indications: treatment of adults and pediatric patients >= 1 month with aHUS

Ultomiris indications: treatment of adult patients with gMG who are anti-AChR antibody-positive

Ultomiris indications: treatment of adult patients with NMOSD who are anti-AQP4 antibody positive

Ultomiris limitation: not indicated for STEC-HUS

Paroxysmal Nocturnal Hemoglobinuria (PNH) - Continuation of Therapy

Covered when ALL of the following are met:

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, etc.)

Requested product is dosed according to the US FDA labeled dosing for PNH

PiaSky-specific: For PiaSky authorization only: 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

Generalized Myasthenia Gravis (gMG) - Continuation of Therapy

Covered when ALL of the following are met:

Patient has previously been treated with the requested product

Submission of medical records demonstrating all of the following: improvement and/or maintenance of at least a 2 point improvement in the MG-ADL score from pre-treatment baseline; reduction in signs and symptoms of myasthenia gravis; maintenance, reduction, or discontinuation of doses of baseline immunosuppressive therapy prior to starting the requested product (Note: add-on, dose escalation of IST, or additional rescue therapy from baseline while on the requested product will be considered treatment failure.)

Requested product is dosed according to the US FDA labeled dosing for gMG

Patient is not receiving the requested product in combination with any of the following for the same indication: a different complement C5 inhibitor or an FcRn blocker

Prescribed by, or in consultation with, a neurologist

Reauthorization will be for no more than 12 months

Neuromyelitis Optica Spectrum Disorder (NMOSD) - Continuation of Therapy

Covered when ALL of the following are met:

Patient has previously been treated with the requested product

Documentation of positive clinical response from baseline as demonstrated by at least both: reduction in the number and/or severity of relapses or signs and symptoms of NMOSD; and maintenance, reduction, or discontinuation of doses of any baseline immunosuppressive therapy prior to starting the requested product (Note: add-on, dose escalation of IST, or additional rescue therapy while on the requested product will be considered treatment failure.)

Requested product is dosed according to the US FDA labeled dosing for NMOSD

Prescribed by, or in consultation with, a neurologist

Patient is not receiving the requested product in combination with disease modifying therapies FDA approved for MS; anti-IL6 therapy; or B-cell depletion therapy

Reauthorization will be for no more than 12 months

For gMG: positive anti‑AChR serology

For NMOSD: positive AQP4‑IgG (NMO‑IgG) serology and neurologist confirmation

To rule out TTP when evaluating aHUS: ADAMTS13 testing (to exclude severe ADAMTS13 deficiency)

To rule out STEC‑HUS when evaluating aHUS: Shiga toxin testing and relevant stool studies as indicated

Relevant baseline labs and signs/symptoms (e.g., platelet count, LDH, hemoglobin, creatinine, evidence of hemolysis/thrombotic microangiopathy)

Documentation Required

Clinical Response Documentation for Continuation

Document clinical response from baseline to support continuation of therapy; use indication‑specific outcome measures where applicable.

aHUS: reduction in need for plasma exchange/pheresis or dialysis, improvement in platelet count, reduced markers of hemolysis, stabilization or improvement in renal function
gMG: improvement of ≥2 points in MG‑ADL from baseline and reduction in signs/symptoms of myasthenia gravis; ability to maintain or reduce baseline immunosuppressive therapy (add‑on or escalation counts as treatment failure)
NMOSD: reduction in number and/or severity of relapses and improvement in signs/symptoms compared to baseline
PNH: increased or stabilized hemoglobin, reduction in transfusion requirements, decreased LDH, reduced hemolysis, increased reticulocyte count

Billing Rule

Dosing per US FDA Labeling

Requested product must be administered and dosed according to the US FDA‑approved labeling for the specific indication.

Dosing must match the FDA‑labeled regimen for the requested indication and product
Deviation from labeled dosing may result in denial or request for supporting rationale and evidence

Denial Risk

Not Covered for STEC‑HUS

Use of complement inhibitors for Shiga toxin E. coli related HUS (STEC‑HUS) is considered not medically necessary and may be denied.

STEC‑HUS (Shiga toxin E. coli related HUS) — Bkemv, Epysqli, PiaSky, Soliris, Ultomiris: not covered

Prior Authorization

REMS Enrollment Required for Prescribers

Prescribers must enroll in and comply with the Risk Evaluation and Mitigation Strategy (REMS) programs where required prior to prescribing REMS‑listed complement inhibitors; include REMS contact information and list of REMS products.

REMS enrollment required for prescribers when applicable
REMS‑listed products: Bkemv (eculizumab‑aeeb), Epysqli (eculizumab‑aagh), PiaSky (crovalimab‑akkz), Soliris (eculizumab), Ultomiris (ravulizumab‑cwvz)
REMS program contact: refer to each product’s FDA REMS webpage or manufacturer contact for enrollment and telephone support

Documentation Required

Meningococcal Vaccination Documentation and Timing

Document meningococcal vaccination prior to initiating therapy and counsel patients about meningococcal infection risk. Vaccination should occur ≥2 weeks before the first dose when possible; if urgent treatment is required, vaccinate as soon as possible and provide appropriate prophylactic measures. Record revaccination per ACIP recommendations and monitor for signs of infection during therapy.

Meningococcal vaccination: document vaccine type(s) administered and dates (conjugate and serogroup B as indicated)
Timing: ideally ≥2 weeks before initiating complement inhibitor therapy; if urgent, vaccinate immediately and document prophylaxis given
Revaccination: follow ACIP guidance for booster doses and revaccination intervals
Clinical monitoring: educate patient to seek immediate care for fever or signs of meningococcal infection

Documentation Required

PiaSky — Special Restrictions

PiaSky (crovalimab) has additional, product‑specific restrictions. Authorization for PiaSky (PNH indication) requires prior trial and failure, contraindication, or intolerance to an approved complement C5 inhibitor, Empaveli (pegcetacoplan), or Fabhalta (iptacopan); PiaSky must not be given in combination with a complement factor D inhibitor (e.g., Voydeya). For continuation, the patient must not be on prohibited combinations and must demonstrate clinical benefit as specified for PNH.

PiaSky (PNH) initial requirement: 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)
PiaSky must not be used in combination with a complement factor D inhibitor (e.g., Voydeya/danicopan) for the same indication
For continuation of PiaSky: document clinical benefit (PNH metrics), and patient must not be receiving prohibited combination therapies
Prescribing specialty for PiaSky: hematologist or oncologist as specified in policy

Denial Risk

Review at Launch — Coverage Limitations for Bkemv and Epysqli

Bkemv (eculizumab‑aeeb) and Epysqli (eculizumab‑aagh) have been added to the Review at Launch program; coverage for these products may be limited and some members may not be eligible. Refer to the insurer’s Review at Launch policy for details; requests may be denied under the Review at Launch process.

Bkemv and Epysqli subject to Review at Launch — coverage may be restricted or deferred
Refer to UnitedHealthcare Medical Benefit Drug Policy: Review at Launch for New to Market Medications for specifics

Full citations and prescribing information are listed in the policy references section and have been updated to reflect current information.

ACIPAdvisory Committee on Immunization Practices — provides vaccine recommendations including meningococcal vaccination schedules for patients receiving complement inhibitors

Added HCPCS Q-codes Q5151 (eculizumab-aagh, Epysqli) and Q5152 (eculizumab-aeeb, Bkemv) to applicable procedure code list.

2025-09-01coverage_language_revisionLatest

Replaced product-specific failure and combination therapy prohibitions with broader language referencing 'a complement C5 inhibitor therapy' and prohibiting combination use of the requested product with a different complement C5 inhibitor or specified classes (e.g., C3 inhibitors, factor B inhibitors, FcRn blockers) for the same indication.

2025-09-01indication_specific_changeLatest

Revised PNH criteria to allow coverage when patient has history of trial and failure, contraindication, or intolerance to a complement C5 inhibitor (examples listed).

2025-09-01indication_specific_changeLatest

Revised gMG criteria: changed prior-failure requirement from failing Soliris or Ultomiris to failing a complement C5 inhibitor therapy (examples include Bkemv, Epysqli, Soliris, Ultomiris, or Zilbrysq) and expanded combination-prohibition language to include FcRn blockers.

2025-09-01indication_specific_changeLatest

Revised NMOSD criteria: changed prior-failure wording to 'failed a complement C5 inhibitor therapy for NMOSD' (examples listed) and updated combination-prohibition wording related to MS disease-modifying therapies.

2025-09-01vaccination_and_remsLatest

Added/clarified meningococcal vaccination and monitoring guidance (vaccinate per ACIP; immunize unvaccinated patients at least 2 weeks before first dose of Soliris or Ultomiris or vaccinate as soon as possible if urgent therapy) and mandated prescriber enrollment in REMS programs for Bkemv, Epysqli, PiaSky, Soliris, and Ultomiris with REMS contact information provided.

2025-09-01references_updateLatest

Updated FDA and References sections to reflect current prescribing information and supporting documents.