OpenPayer is powered by Trek Health's payer performance platform. Trek continuously ingests, validates, and normalizes Transparency in Coverage data alongside payer policies and other commercial payer data to create a structured payer intelligence foundation. OpenPayer uses this foundation to deliver personalized search results, dynamically generated policy pages, and tailored policy monitoring based on each user's payers, specialties, billing codes, and areas of interest. The same intelligence powers broader payer performance workflows, including reimbursement benchmarking, contract evaluation, payer negotiations, and financial decision-making.

Modifiedsierra health and lifePolicy 2026D0049AE

Complement C5 Inhibitors

Customize your policy alerts

Sign up for sierra health and life Policy 2026D0049AE alerts

Get alerted when Policy 2026D0049AE changes without checking for updates manually.

Monitor payer policy activity

Receive email alerts as soon as relevant payer policies are published or updated.

Coverage and medical necessity criteria for complement C5 inhibitor drugs (Bkemv, Epysqli, PiaSky, Soliris, Ultomiris) for Sierra Health and Life members under the medical benefit; includes diagnosis-specific criteria and preferred product rules.

Policy Summary

Payersierra health and life

PolicyComplement C5 Inhibitors

Policy CodePolicy 2026D0049AE

Change TypeContinuation & initial criteria revised

Effective DateApr 1, 2026

Next Review DateN/A

Key ActionSubmit prior authorization with documentation of indication-specific criteria, REMS enrollment, meningococcal vaccination, and evidence of positive clinical response or preferred-product trial/intolerance as applicable.

SourceLink

POLICY UPDATE CHANGES

Revised continuation of therapy criteria for aHUS to require either being on Soliris and meeting Preferred Product Criteria or being on Bkemv, Epysqli, or Ultomiris; removed requirement that the patient previously was treated with the requested product.

Revised continuation of therapy criteria for PNH to require either being on Soliris and meeting Preferred Product Criteria or being on Bkemv, Epysqli, PiaSky, or Ultomiris; removed requirement that the patient previously was treated with the requested product.

Added requirement that patient is not receiving the requested product in combination with B-cell depletion therapy (e.g., inebilizumab) or an immune globulin for the same indication.

Removed initial therapy criterion requiring history of at least two relapses in prior 12 months or three relapses in 24 months (with one in past 12 months).

Policy title changed from 'Complement Inhibitors' (previous title) and summary of changes recorded in policy history.

5products named

12 monthsmax auth period

14 wkspreferred trial

≥6gMG MG-ADL threshold

REMSREMS required

Coverage and Medical Necessity Criteria

Preferred Product Criteria (Soliris exceptions)

Soliris is medically necessary only when either of the following alternative pathways are met:

Preferred-product failure or intolerance: Either: (1) Both: documentation of a trial of at least 14 weeks of Bkemv and Epysqli with minimal clinical response and residual disease activity; AND physician attestation that the clinical response would be expected to be superior with Soliris; OR (2) Both: documentation of intolerance, contraindication, or adverse event to Bkemv and Epysqli; AND physician attestation that the same intolerance/contraindication/adverse event would not be expected with Soliris.>= 14 weeks

Patient must not have had loss of a favorable response after established maintenance therapy with an eculizumab product

aHUS — Initial and Continuation Therapy

Covered when ALL of the following are met

Initial Therapy for aHUS: (1) Documentation ruling out STEC-HUS and TTP (e.g., ADAMTS13 deficiency); AND (2) Laboratory results, signs, or symptoms attributable to aHUS (e.g., thrombocytopenia, microangiopathic hemolysis, thrombotic microangiopathy, acute renal failure); AND (3) Patient is treatment‑naive to the requested product; AND (4) Requested product dosed per US FDA labeled dosing for aHUS; AND (5) Prescribed by or in consultation with a hematologist or nephrologist; AND (6) Initial authorization ≤ 12 months.

Policy Summary

Payersierra health and life

PolicyComplement C5 Inhibitors

Policy CodePolicy 2026D0049AE

Change TypeContinuation & initial criteria revised

Effective DateApr 1, 2026

Next Review DateN/A

SourceLink

On This Page

PNH — Initial and Continuation Therapy

Covered when ALL of the following are met

Initial Therapy for PNH: (1) Flow cytometry confirming presence of PNH clones; AND (2) Laboratory results, signs, or symptoms attributable to PNH (e.g., abdominal pain, anemia, dyspnea, fatigue, thrombosis, hemolysis/hemoglobinuria, kidney disease, pulmonary hypertension); AND (3) Requested product dosed per US FDA labeled dosing for PNH; AND (4) Patient is not receiving the requested product in combination with a different complement C5 inhibitor, a complement C3 inhibitor (e.g., pegcetacoplan), or a complement factor B inhibitor (e.g., iptacopan); AND (5) For PiaSky only: history of trial and failure, contraindication, or intolerance to one of the listed agents; AND (6) Prescribed by or in consultation with a hematologist or oncologist; AND (7) Initial authorization ≤ 12 months.<= 12 months

Continuation of Therapy for PNH: (1) One of the following: patient is on Soliris and meets the Preferred Product Criteria OR patient is on Bkemv, Epysqli, PiaSky, or Ultomiris; AND (2) Documentation demonstrating a positive clinical response from baseline (e.g., increased/stabilized hemoglobin, reduction in transfusions, improvement in hemolysis, decrease in LDH); AND (3) Requested product dosed per US FDA labeled dosing for PNH; AND (4) Patient is not receiving the requested product in combination with disallowed agents (different complement C5 inhibitor, complement C3 inhibitor, or complement factor B inhibitor); AND (5) For PiaSky: patient is not receiving PiaSky with a complement factor D inhibitor (e.g., danicopan); AND (6) Prescribed by or in consultation with a hematologist or oncologist; AND (7) Reauthorization ≤ 12 months.<= 12 months

gMG (anti-AChR positive) — Initial and Continuation Therapy

Covered when ALL of the following are met

Initial Therapy for gMG (anti-AChR positive): (1) Medical records confirming no prior failure of a complement C5 inhibitor; AND (2) Diagnosis of generalized myasthenia gravis; AND (3) Positive anti‑AChR serology; AND (4) MGFA clinical classification II–IV at initiation; AND (5) MG‑ADL total score ≥ 6 at initiation; AND (6) One of the following: history of failure of at least two immunosuppressive agents over ≥12 months OR failure of at least one immunosuppressive plus ≥4 courses of plasmapheresis/IVIG over ≥12 months without control; AND (7) Requested product initiated and titrated per US FDA labeled dosing for gMG; AND (8) Patient is not receiving the requested product in combination with excluded agents (B‑cell depletion, another complement C5 inhibitor, complement C3 or factor B inhibitors, FcRn blockers, immune globulin); AND (9) Prescribed by or in consultation with a neurologist; AND (10) Initial authorization ≤ 12 months.>= 6 (MG-ADL); <= 12 months

Continuation of Therapy for gMG: (1) One of the following: patient is on Soliris and meets the Preferred Product Criteria OR patient is on Bkemv, Epijkstra (Epysqli), or Ultomiris; AND (2) Documentation demonstrating a positive clinical response from baseline; AND (3) Requested product dosed per US FDA labeled dosing for gMG; AND (4) Prescribed by or in consultation with a neurologist; AND (5) Reauthorization ≤ 12 months.<= 12 months

gMG — Continuation of Therapy

Covered when ALL of the following are met:

gMG continuation criteria: Submission of medical records demonstrating: (1) improvement and/or maintenance of at least a 2‑point improvement in MG‑ADL from pre‑treatment baseline; AND (2) reduction in signs and symptoms of myasthenia gravis; AND (3) maintenance, reduction, or discontinuation of baseline immunosuppressive therapy prior to starting the requested product (add on, dose escalation, or additional rescue therapy while on the product is considered treatment failure); AND (4) Requested product dosed per US FDA labeled dosing for gMG; AND (5) Patient is not receiving the requested product in combination with listed agents (B‑cell depletion, a different complement C5 inhibitor, FcRn blocker, or immune globulin); AND (6) Prescribed by or in consultation with a neurologist; AND (7) Reauthorization ≤ 12 months.MG-ADL >=2-point improvement

Add on/escalation of baseline IST considered treatment failure

NMOSD — Initial and Continuation Therapy

Initial therapy covered when ALL of the following are met:

NMOSD initial criteria: (1) Diagnosis of NMOSD by a neurologist with qualifying clinical history (optic neuritis, acute myelitis, area postrema syndrome, acute brainstem syndrome, symptomatic narcolepsy/diencephalic syndrome, or symptomatic cerebral syndrome); AND (2) Positive anti‑AQP4 (AQP4‑IgG/NMO‑IgG) serology; AND (3) Alternative diagnoses including multiple sclerosis ruled out; AND (4) Patient has not failed prior complement C5 inhibitor therapy for NMOSD; AND (5) History of failure/contraindication/intolerance to rituximab (Medicare: see CMS guidance); AND (6) Requested product initiated/titrated per US FDA labeled dosing for NMOSD; AND (7) Patient is not receiving the requested product in combination with excluded agents (anti‑IL6, B‑cell depletion, MS disease‑modifying therapies); AND (8) Prescribed by or in consultation with a neurologist; AND (9) Initial authorization ≤ 12 months.

NMOSD continuation entry: For continuation, one of the following: patient is on Soliris and meets the Preferred Product Criteria OR patient is on Bkemv, Epijkstra (Epijkstra/Epigslist?), or Ultomiris.

NMOSD continuation response: Documentation of positive clinical response from baseline demonstrated by: (1) reduction in number and/or severity of relapses or signs/symptoms of NMOSD; AND (2) maintenance, reduction, or discontinuation of baseline IST prior to starting the requested product (add on/dose escalation/additional rescue therapy while on product considered treatment failure); AND (3) Requested product dosed per US FDA labeled dosing for NMOSD; AND (4) Prescribed by or in consultation with a neurologist; AND (5) Patient is not receiving the requested product in combination with excluded agents (anti‑IL6, B‑cell depletion, MS DMTs); AND (6) Reauthorization ≤ 12 months.

Evidence-supported coverage (PNH)

PNH clinical trial findings relevant to coverage:

Long-term eculizumab outcomes: Long‑term eculizumab treatment produced sustained LDH reductions (median 86.9% at 36 months), decreased thrombotic events (TEs) by 81.8%, improved or stabilized CKD stage in 93.1% at 36 months, and increased transfusion independence by 90%.

Chunks 36–37

Pegcetacoplan vs eculizumab (PEGASUS): Pegcetacoplan was superior to eculizumab for hemoglobin increase (mean difference 3.84 g/dL) and transfusion avoidance (85% vs 15%) in patients with persistent anemia on eculizumab (PEGASUS trial).

Chunks 38–39

Crovalimab (COMMODORE 2): Crovalimab demonstrated noninferiority to eculizumab for hemolysis control (LDH ≤1.5x ULN) and had similar rates of breakthrough hemolysis and hemoglobin stabilization in adults; pediatric results were consistent with adults.

Chunks 40–41

Initial Therapy — Indication-specific Requirements

Initial therapy

Indication‑specific initial therapy criteria require diagnostic confirmation, dosing per FDA labels, specialty prescribing, and initial authorizations:

Diagnostic confirmation: Submit documentation supporting the specific diagnosis (e.g., flow cytometry for PNH; rule‑out of STEC‑HUS and TTP for aHUS; positive AQP4‑IgG for NMOSD; positive anti‑AChR for gMG) and baseline measures of disease activity.

Dosing and prescriber: Requested product must be initiated and titrated according to US FDA labeled dosing for the indication; prescribed by or in consultation with the appropriate specialist (hematologist, nephrologist, neurologist, or oncologist as applicable).

Initial authorization period: Initial authorizations will be for no more than 12 months per indication-specific criteria.<= 12 months

Initial therapy — NMOSD

NMOSD initial therapy requires neurologist involvement and serologic confirmation:

NMOSD initial - neurology requirement: Diagnosis of NMOSD must be made by a neurologist confirming a qualifying clinical syndrome and positive AQP4‑IgG serology; multiple sclerosis and other diagnoses must be ruled out; history of failure/contraindication/intolerance to rituximab should be documented when applicable per CMS guidance; dosing per US FDA label; prescribed by or in consultation with a neurologist; initial authorization ≤ 12 months.

Initiation prerequisites

Initiation prerequisites and precautions for complement inhibitors:

Meningococcal vaccination: Complete or update meningococcal vaccination at least 2 weeks prior to the first dose when possible; if urgent therapy is indicated, vaccinate as soon as possible and monitor closely per FDA/ACIP guidance.2 weeks preferred

REMS prescriber enrollment: Prescribers must enroll in the product‑specific REMS program prior to prescribing/dispensing these agents; verify REMS enrollment during prior authorization and document vaccination status.

Initial Therapy

Initial therapy criteria updated:

Initial Therapy - update: Removed the prior requirement for historic relapse counts as a condition for initiation (i.e., no longer requires ≥2 relapses in prior 12 months or ≥3 relapses in prior 24 months with one in past 12 months).

Continuation Therapy — Renewal Requirements

Continuation therapy

Continuation requests across indications require demonstration of ongoing benefit and specialty prescribing:

General continuation requirements: Documentation demonstrating positive clinical response from baseline; dosing per US FDA labeled dosing; prescribed by or in consultation with the appropriate specialist; reauthorization up to 12 months; patients on Soliris must meet Preferred Product Criteria to remain on Soliris.

Continuation requirements

Continuation requires showing clinical benefit and adherence to combination‑therapy exclusions:

Continuation requirements: Continuation requires documentation of clinical benefit (measure varies by indication, e.g., MG‑ADL improvement, reduction in relapses or transfusions, LDH control), dosing per US FDA label, prescribed by appropriate specialist, reauthorization ≤ 12 months; patient must not be receiving the requested product in combination with excluded agents (B‑cell depletion, immune globulin, other complement inhibitors, complement C3/factor B inhibitors, anti‑IL6, MS DMTs as applicable).

Eculizumab continuation

Long‑term evidence for eculizumab supports continuation in PNH:

Eculizumab continuation evidence: Long‑term eculizumab studies demonstrated sustained reductions in hemolysis (median LDH reduction 86.9% at 36 months), decreased thrombotic events, improved/stabilized renal function, and increased transfusion independence, supporting continued therapy in responders.

Continuation Therapy — complement inhibitors

Continuation therapy rules updated:

Continuation - complement inhibitors (updated): Patient is not receiving the requested product in combination with B‑cell depletion therapy (e.g., inebilizumab) or an immune globulin for the same indication; AND one of the following depending on indication: patient is on Soliris and meets the Preferred Product Criteria OR patient is currently on one of the specified alternatives (Bkemv, Epysqli, PiaSky, or Ultomiris as applicable).

Removed prior requirement that patient previously was treated with the requested product.

Prior Authorization, Documentation, and Provider Responsibilities

Prior Authorization

Prior authorization required; Soliris contingent on Preferred Product Criteria

Prior authorization is required for Soliris; coverage for Soliris is contingent on meeting the Preferred Product Criteria (trial of preferred eculizumab products for ≥14 weeks with minimal response plus physician attestation, or documentation of intolerance/contraindication to both preferred products with physician attestation). Members already on Soliris must change to preferred products (Bkemv or Epysqli) unless they meet the Preferred Product Criteria for continued Soliris use.

Preferred eculizumab products: Bkemv (eculizumab-aeeb) and Epysqli (eculizumab-aagh).
Soliris coverage allowed only if Preferred Product Criteria met (14-week trial failure OR intolerance/contraindication + physician attestation; patient must not have had loss of favorable response after established maintenance).

Prior Authorization

Prior authorization required; authorization typically ≤ 12 months

Submit prior authorization with documentation that the request meets the indication-specific initial or continuation criteria. Initial authorizations and reauthorizations are limited to no more than 12 months per the policy.

Include diagnosis confirmation, specialist prescribing (hematologist/nephrologist/neurologist/oncologist as applicable), and FDA‑label dosing.
Reauthorization requests must document ongoing clinical benefit; authorizations are typically for up to 12 months.

Prior Authorization

Confirm prescriber REMS enrollment and meningococcal vaccination

Prior authorization must confirm prescriber enrollment in the product-specific REMS program and that meningococcal vaccination has been addressed per FDA/ACIP guidance (vaccinate ≥2 weeks prior to first dose when possible; if urgent, vaccinate as soon as possible and monitor).

REMS enrollment contact/web details: Bkemv (1-866-718-6927 / http://www.bkemvrems.com), Epysqli (1-866-318-0342 / http://www.epysqlirems.com), PiaSky (1-866-469-7599 / http://www.piaskyrems.com), Soliris/Ultomiris (1-888-765-4747 / http://www.solirisrems.com or www.ultomirisrems.com).
Follow ACIP recommendations for meningococcal vaccination and revaccination as applicable.

Prior Authorization

Continuation requests must show current use on Soliris meeting Preferred Criteria or on specified alternatives

Continuation authorization must document that the patient is either currently on Soliris and meets the Preferred Product Criteria or is currently using one of the specified alternative products (Bkemv, Epysqli, PiaSky, or Ultomiris as applicable per indication).

Policy removed prior requirement that the patient previously received the requested product; current use on an allowed product or meeting Soliris Preferred Product Criteria is sufficient.
Documentation of positive clinical response from baseline is required for continuation.

Step Therapy

Therapeutic interchange: Soliris patients may need to switch to preferred eculizumab products

Members currently receiving Soliris may be required to switch to preferred eculizumab products (Bkemv or Epijkstra/Epysqli) unless continuation-on-Soliris criteria are met (preferred-product trial failure/intolerance with physician attestation or predicted superior response).

Preferred products named in policy: Bkemv (eculizumab-aeeb) and Epysqli (eculizumab-aagh).
A documented trial of at least 14 weeks of both preferred products with minimal clinical response supports switching to Soliris.

Step Therapy

NMOSD initial therapy: no prior C5 inhibitor failure and document rituximab status

For NMOSD initial therapy, the patient must not have failed prior complement C5 inhibitor therapy for NMOSD and must have documented history of failure, contraindication, or intolerance to rituximab (with Medicare reviews referencing CMS guidance).

Required NMOSD diagnostics: neurologist diagnosis with qualifying clinical syndromes and positive AQP4‑IgG serology; MS and other diagnoses ruled out.
Document rituximab failure/contraindication/intolerance or rationale if not tried.

Note

Clinical trial evidence may support step decisions or switching

The policy notes that head‑to‑head and active‑controlled clinical trials (e.g., pegcetacoplan vs eculizumab, crovalimab vs eculizumab) may inform step or preferred therapy decisions and support switching when evidence of superior response exists.

PEGASUS showed pegcetacoplan superior to eculizumab for hemoglobin increase and transfusion avoidance in patients with persistent anemia on eculizumab.
COMMODORE 2 demonstrated crovalimab noninferiority to eculizumab for hemolysis control.

Note

Medicare Advantage: preferred-product criteria not applicable

Preferred therapy criteria do not apply to Medicare Advantage members; Medicare reviews should follow CMS/local guidance instead.

Medicare Part B coverage rules for outpatient physician‑administered drugs remain applicable; refer to LCDs/LCAs and Medicare Benefit Policy Manual.
Preferred-product rules are not applicable for Medicare Advantage per CMS guidance.

Documentation Required

Provide medical records, labs, and diagnostic confirmation with PA

Include submission of medical records (chart notes, laboratory values, flow cytometry for PNH, ADAMTS13 to rule out TTP, etc.) to confirm diagnosis-specific criteria and baseline disease activity when requesting prior authorization.

PNH: flow cytometry confirming PNH clones plus labs/signs attributable to PNH.
aHUS: documentation ruling out STEC‑HUS and TTP (e.g., ADAMTS13) and labs consistent with aHUS.

Documentation Required

For continuation, document clinical improvement/maintenance (e.g., MG‑ADL improvement)

For continuation requests, submit documentation demonstrating clinical improvement or maintenance from baseline (e.g., MG‑ADL ≥2‑point improvement for gMG, reduction in relapses/signs for NMOSD) and documentation of maintenance/reduction/discontinuation of baseline IST prior to starting the requested product.

gMG continuation requires ≥2‑point MG‑ADL improvement from pretreatment baseline and reduction in signs/symptoms.
NMOSD continuation requires reduction in number/severity of relapses or signs/symptoms plus IST maintenance/reduction/discontinuation documentation.

Documentation Required

Document meningococcal vaccination and REMS enrollment evidence

Document meningococcal vaccination status according to ACIP recommendations and include evidence of prescriber REMS enrollment for REMS‑restricted products (Bkemv, Epijkstra/Epysqli, PiaSky, Soliris, Ultomiris) prior to initiation when possible; if urgent therapy is given, document vaccine administration and monitoring plans.

Vaccinate at least 2 weeks prior to first dose when possible; revaccinate per ACIP as indicated.
If urgent, vaccinate as soon as possible and monitor closely for invasive meningococcal disease.

Documentation Required

Document prescriber REMS enrollment (contact/web details provided)

Include documentation of prescriber enrollment in the applicable REMS program for REMS-restricted products; REMS enrollment contact numbers and websites are provided in the policy.

REMS enrollment resources: see Bkemv, Epijkstra/Epysqli, PiaSky, Soliris, Ultomiris contact/web details in the REMS section.
Lack of documented REMS enrollment may delay or prevent dispensing.

Documentation Required

For aHUS, document exclusion of STEC‑HUS and TTP

For aHUS, the provider must document exclusion of STEC‑HUS and TTP (e.g., ADAMTS13 testing) as part of diagnostic confirmation prior to authorization.

Policy explicitly requires ruling out Shiga toxin E. coli–related HUS (STEC‑HUS) and thrombotic thrombocytopenic purpura (TTP).
Provide laboratory and clinical evidence supporting aHUS diagnosis.

Denial Risk

STEC‑HUS: complement inhibitors considered unproven and not medically necessary

The policy states that complement C5 inhibitors are unproven and not medically necessary for STEC‑HUS; requests for STEC‑HUS will not meet coverage criteria.

Soliris, Bkemv, Epysqli, PiaSky, and Ultomiris are not indicated for STEC‑HUS per FDA/ policy statements.
Do not submit PA for STEC‑HUS expecting approval for complement inhibitor therapy.

Denial Risk

Treatment failure includes addition/escalation of baseline IST or rescue therapy

Treatment failure for continuation is defined to include addition or escalation of baseline immunosuppressive therapy (IST) or use of additional rescue therapy from baseline to treat disease or exacerbation while on the requested product; such scenarios may be considered treatment failure and lead to denial.

Add‑on therapy, dose escalation of baseline IST, or additional rescue therapy while on the requested product will be considered treatment failure.
Document maintenance, reduction, or discontinuation of baseline IST prior to starting the requested product for continuation approval.

Denial Risk

Absence of meningococcal vaccination or REMS enrollment may cause denial or delay

Lack of required meningococcal vaccination or lack of prescriber REMS enrollment may result in denial of coverage or inability to dispense REMS‑restricted complement inhibitors.

Vaccination per ACIP and REMS enrollment should be documented prior to initiation when possible.
If urgent treatment is provided without prior vaccination, document vaccination timing and monitoring plans.

Denial Risk

Combination therapy with B‑cell depletion or immune globulin excluded and may cause denial

Coverage may be denied if the requested complement inhibitor is being used in combination with a B‑cell depletion therapy (e.g., inebilizumab) or an immune globulin for treatment of the same indication; continuation rules explicitly require patients not be receiving such combination therapy.

Continuation criteria added requirement that patient not receive requested product in combination with B‑cell depletion therapies or immune globulin.
Document that the patient is not receiving the requested product concurrently with excluded agents.

Denial Risk

Prescriber REMS enrollment is required; non‑enrollment may trigger denial or delay

Prescriber non‑enrollment in the applicable REMS program for Bkemv, Epijkstra/Epysqli, PiaSky, Soliris, or Ultomiris may trigger denial or delay; include REMS enrollment documentation with the prior authorization.

REMS enrollment is a requirement under the restricted programs for these agents; contact details and websites are in the policy.
Lack of prescriber REMS enrollment is listed as a denial risk.

Relevant Procedure and Diagnosis Codes

Applicable procedure and diagnosis codes referencedmixed

J1299	Injection, eculizumab, 2 mg.
J1303	Injection, ravulizumab-cwvz, 10 mg.
J1307	Injection, crovalimab-akkz, 10 mg.
Q5151	Injection, eculizumab-aagh (epijski), biosimilar, 2 mg.
Q5152	Injection, eculizumab-aeeb (bkemv), biosimilar, 2 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].

1–10 of 12

1/2

Drugs discussed (no billing codes listed in this section)NDC | other

No codes listed

inv-24: MG-ADL threshold used for gMG initiation and continuation assessments

MG-ADL initiation thresholdMG-ADL total score ≥ 6 at initiation of therapy

MGFA class requirementMGFA Clinical Classification II–IV at initiation

Prior C5 inhibitorPatient has not failed a previous course of a complement C5 inhibitor prior to initiation

inv-25: Preferred product trial duration — minimum trial duration before switching to Soliris.

Minimum preferred product trial durationAt least 14 weeks trial of Bkemv and Epysqli with minimal clinical response required before Soliris consideration

Trial documentationPhysician attestation required that Soliris would be expected to be superior to prior response

Exception pathAlternatively, documentation of intolerance/contraindication to Bkemv and Epysqli with physician attestation may permit Soliris

inv-26: Platelet count — trial inclusion value referenced for aHUS studies.

Platelet count inclusion (aHUS trials)Platelet count ≤ 150 x 10^9 /L required in the referenced ravulizumab aHUS study

Additional enrollment criteriaEvidence of hemolysis (elevated LDH) and serum creatinine above ULN or dialysis requirement were also required in the study

Complete TMA response componentsNormalization of platelet count and LDH plus ≥25% improvement in serum creatinine were used as endpoints

inv-27: LDH hemolysis control threshold — hemolysis control definition (≤1.5x ULN).

LDH hemolysis control threshold (trial definition)Hemolysis control defined as LDH ≤ 1.5x upper limit of normal (ULN)

Measurement periodMean proportion of patients with LDH ≤ 1.5x ULN from week 5 to week 25 used in crovalimab trial

Related endpointsUsed alongside transfusion avoidance and breakthrough hemolysis endpoints

inv-28: Hemoglobin entry threshold in PEGASUS trial (pegcetacoplan study).

Hemoglobin entry threshold (PEGASUS)Hemoglobin < 10.5 g/dL despite prior eculizumab treatment ≥ 3 months

Prior therapy requirementPatients had received eculizumab for at least 3 months before enrollment in the pegcetacoplan trial

Primary endpoint contextTrial enrolled patients with persistent anemia on eculizumab to compare hemoglobin response and transfusion avoidance

Step Therapy and Therapeutic Interchange Rules

Step	Requirement	Duration / Evidence	Coverage status
1
Trial of preferred eculizumab products (Bkemv and Epysqli) prior to Soliris OR documentation of intolerance/contraindication to both preferred eculizumab products with physician attestation that Soliris would be expected to be effective or that the same intolerance would not occur with Soliris.
>= 14 weeks trial of both Bkemv and Epysqli to demonstrate minimal clinical response; alternatively, documented intolerance/contraindication with supporting clinician attestation.
Coverage allowed when criteria met

Step	Requirement	Applies to	Coverage status
1
Documentation of history of failure, contraindication, or intolerance to rituximab (or documented reason for not using rituximab) prior to coverage for NMOSD initial therapy; include clinician attestation and supporting records.
Required for NMOSD initial therapy per policy; Medicare reviews should reference CMS guidance where applicable.
Coverage allowed when documented

Step	Guidance	Supporting evidence	Coverage status
1
Consider switching to or using an alternative complement inhibitor (e.g., pegcetacoplan, crovalimab) when there is inadequate clinical or laboratory response to prior C5 inhibitor therapy; document rationale and trial data supporting the switch.
Pegcetacoplan demonstrated superiority to eculizumab for hemoglobin increase and transfusion avoidance (PEGASUS); crovalimab showed noninferiority to eculizumab for hemolysis control (COMMODORE 2).
May support coverage when documented and clinically justified

Biosimilar / Preferred Product Information

Billing Rule

Soliris (eculizumab)

Bkemv and Epijkstra (eculizumab biosimilars) are designated as the preferred eculizumab products; members on Soliris may be required to switch to these preferred products unless they meet the Soliris Preferred Product Criteria for continuation.

Preferred eculizumab products: Bkemv (eculizumab‑aeeb) and Epijkstra (eculizumab‑aagh).
Document Preferred Product Criteria exceptions (trial failure or intolerance) to retain Soliris.

Billing Rule

eculizumab (J1299)

Eculizumab billing codes include J1299 for injection eculizumab (2 mg) and biosimilar codes Q5151 and Q5152; coverage of these J/Q codes is subject to meeting the policy's clinical criteria.

J1299 — Injection, eculizumab, 2 mg.
Q5151/Q5152 — biosimilar eculizumab injections; submit clinical documentation per policy for coverage.

Definitions and Key Terms

inv-48: aHUS — definition and diagnostic exclusion requirements.

aHUS definitionAtypical hemolytic uremic syndrome is a complement-mediated thrombotic microangiopathy (TMA) requiring exclusion of STEC-HUS and TTP (e.g., ADAMTS13 deficiency)

Diagnostic exclusion requirementsDocumentation must rule out Shiga toxin E. coli–related HUS (STEC-HUS) and thrombotic thrombocytopenic purpura (TTP) for aHUS initial therapy

Specialist prescribingTherapy must be prescribed by or in consultation with a hematologist or nephrologist

inv-49: PNH — brief definition and diagnostic confirmation methods.

PNH definitionParoxysmal nocturnal hemoglobinuria: diagnosis confirmed by flow cytometry demonstrating presence of PNH clones with associated hemolytic symptoms or thrombosis

Diagnostic confirmation methodFlow cytometry analysis confirming PNH clones is required for initial therapy authorization

Clinical evidence requirementDocumentation of laboratory results, signs, and/or symptoms attributable to PNH (e.g., anemia, hemoglobinuria, unexplained thrombosis) must be provided

inv-50: gMG (anti-AChR positive) — definition, MGFA class and MG-ADL threshold.

gMG (anti-AChR positive) definitionGeneralized myasthenia gravis with positive anti-AChR serology; MGFA clinical class II–IV at initiation

MG-ADL threshold for initiationMG-ADL total score ≥ 6 at initiation of therapy

Specialist prescribing and prior C5 inhibitorPrescribed by or in consultation with a neurologist; patient must not have failed prior complement C5 inhibitor therapy for initial therapy

inv-51: C5 inhibitor mechanism — mechanism of action summary.

Mechanism of action summaryC5 inhibitors bind complement protein C5, blocking its cleavage to C5a and C5b and preventing formation of the terminal complement complex (C5b-9/MAC)

Therapeutic effect in hemolysisIn PNH, inhibition of terminal complement prevents intravascular hemolysis

Presumed effect in gMGIn gMG, therapeutic effect is presumed to involve reduction of C5b-9 deposition at the neuromuscular junction

inv-52: Breakthrough hemolysis — definition used in policy.

Breakthrough hemolysis definitionA new or worsening symptom or sign of intravascular hemolysis in the presence of elevated LDH ≥ 2x ULN after prior reduction of LDH to ≤ 1.5x ULN on treatment

Context of useUsed as a secondary endpoint in PNH trials to capture recurrent hemolytic events despite prior control

Relation to hemolysis controlBreakthrough hemolysis is defined relative to prior achievement of hemolysis control (LDH ≤ 1.5x ULN)

inv-53: Hemolysis control (trial definition) — definition used in trials (LDH ≤ 1.5x ULN).

Hemolysis control (trial definition)Mean proportion of patients with LDH ≤ 1.5x upper limit of normal (ULN) over the defined trial period

Example measurement periodIn the crovalimab trial, LDH ≤ 1.5x ULN was assessed from week 5 to week 25

Used with other endpointsAssessed alongside transfusion avoidance, breakthrough hemolysis, and hemoglobin stabilization endpoints

inv-54: REMS — Risk Evaluation and Mitigation Strategy definition and prescriber enrollment requirement.

REMS definitionRisk Evaluation and Mitigation Strategy — restricted program requiring prescriber enrollment for these agents

Enrollment requirementPrescribers must enroll in the product-specific REMS program prior to prescribing/dispensing Bkemv, Epysqli, PiaSky, Soliris, or Ultomiris

Vaccination and monitoring linkageREMS guidance accompanies recommendations for meningococcal vaccination and monitoring per FDA/ACIP guidance

Policy Revision History

2026-04-01material_revisionLatest

Revised continuation criteria: aHUS continuation updated to allow continuation if patient is on Soliris and meets Preferred Product Criteria or is on Bkemv, Epysqli, or Ultomiris; removed requirement that patient previously was treated with the requested product.

2026-04-01material_revision

Revised continuation criteria: PNH continuation updated to allow continuation if patient is on Soliris and meets Preferred Product Criteria or is on Bkemv, Epijkstra, PiaSky, or Ultomiris; removed requirement that patient previously was treated with the requested product.

2026-04-01material_revision

Added combination-therapy exclusion to continuation criteria: patient must not be receiving the requested product in combination with B-cell depletion therapy (e.g., inebilizumab) or an immune globulin for the same indication.

2026-04-01material_revision

Removed an initial-therapy eligibility criterion that required a history of at least two relapses in the prior 12 months or three relapses in 24 months (with one in past 12 months).

2026-04-01archive_note

Archived previous policy version 2026D0049AD noted in supporting information.

The policy revision history notes that continuation therapy rules were updated effective 04/01/2026. The change log records that prior versions are archived and that earlier continuation criteria requiring prior receipt of the requested product were removed; continuation now allows patients who are on Soliris and meet Preferred Product Criteria or who are on specified alternate products to qualify for reauthorization.

Complement C5 Inhibitors

Sign up for sierra health and life Policy 2026D0049AE alerts

Coverage and Medical Necessity Criteria

Initial Therapy — Indication-specific Requirements

Continuation Therapy — Renewal Requirements

Prior Authorization, Documentation, and Provider Responsibilities

Relevant Procedure and Diagnosis Codes

Step Therapy and Therapeutic Interchange Rules

Site of Care Notes

Biosimilar / Preferred Product Information

Background and Rationale

Definitions and Key Terms

Policy Revision History