ModifiedPremera BluecrossPolicy N/A

IL-5 Inhibitors (Cinqair, Fasenra, Nucala, Exdensur) - Coverage Criteria

Defines medical necessity, site-of-service review, and coverage criteria for IL-5 inhibitor biologic therapies used as add-on treatment for severe eosinophilic asthma and other eosinophilic conditions; applies to provider requests for pharmacy and medical benefit administration.

Policy Summary

PayerPremera Bluecross

PolicyIL-5 Inhibitors (Cinqair, Fasenra, Nucala, Exdensur) - Coverage Criteria

Policy CodePolicy N/A

Change TypeAdded and revised coverage criteria (includes new agent)

Effective DateApr 1, 2026

Next Review DateN/A

Key ActionSubmit prior authorization with documentation of eosinophil counts and evidence of uncontrolled disease on maximal controller therapy.

SourceLink

POLICY UPDATE CHANGES

Added coverage criteria for Exdensur (depemokimab-ulaa).

Updated list of medications that must not be used concurrently to include Exdensur (depemokimab-ulaa).

Updated age indication and eosinophil threshold changes over time for multiple agents (e.g., Fasenra age to 6 years; eosinophil thresholds changed between 150 and 300 cells/mcL across updates).

Updated EGPA criteria for Fasenra and Nucala from absolute eosinophil count >=1500 cells/mcL to >=1000 cells/mcL.

Added site-of-service reviews and clarified site-of-service criteria can apply to injection drugs and added site-of-service review for Fasenra and Nucala.

Updated asthma management criteria for Cinqair, Fasenra, and Nucala to allow use of oral or systemic corticosteroids for exacerbations and to allow blood eosinophil count >=150 cells/mcL with exceptions for those unable to discontinue corticosteroids for testing.

Added (2026)Exdensur coverage status

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Typical approval length

>=150Common eosinophil threshold

4Named IL‑5 agents

6+/12+/18+Minimum ages vary

Coverage Criteria and Medical Necessity

Initial Authorization and Initiation Requirements

Initial therapy — general

Initial therapy — general common requirements across agents:

Initial therapy common elements: Age requirement per drug/indication (see agent sections); individual must be on maximum tolerated inhaled corticosteroid plus an inhaled LABA (and other controllers as appropriate) AND meet exacerbation history or objective lung function impairment criteria (e.g., >=2 exacerbations requiring oral/systemic steroids in prior 12 months, >=1 exacerbation requiring hospitalization/ED/urgent care, or FEV1 <80% predicted or FEV1/FVC <0.80) AND meet eosinophil phenotype criteria (blood eosinophils >=150 cells/mcL commonly or sputum >=3% as specified) or be systemic corticosteroid–dependent and unable to discontinue for testing; AND prior authorization required; AND not used concurrently with other listed biologics for asthma; AND prescribed by or in consultation with an appropriate specialist; dosing per agent-specific prescribing information.blood eosinophils >=150 cells/mcL (policy default)

Trial populations in pivotal studies often used >=300 cells/µL as primary analysis but benefit noted at >=150 cells/µL in some analyses; prior authorization should verify eosinophil counts and background therapy.

Initiation context

Initiation context — trial-based inclusion and evidence requirements for initiation:

Trial inclusion examples: Pivotal trials enrolled patients uncontrolled on high- or medium-to-high dose ICS plus other controllers, often required baseline elevated blood eosinophils (primary analyses at >=300 cells/µL, though efficacy observed at >=150 cells/µL in subgroups), and included exacerbation history or OCS dependence as inclusion criteria; SYNAPSE required prior nasal corticosteroid use and prior polypectomy history for CRSwNP.see trial protocols

These trial characteristics inform coverage thresholds and documentation expectations; depemokimab trials enrolled individuals >=12 years and used 100 mg SQ at weeks 0 and 26.

Initial therapy evidence

Initial therapy evidence — dosing context and alignment with pivotal trials:

Benralizumab dosing context: Pivotal trials (CALIMA, SIROCCO) used 30 mg subcutaneous injections with initial Q4-week dosing then every 4 or 8 weeks; primary analyses focused on baseline eosinophils >=300 cells/µL with benefit observed in lower-threshold subgroups as well.benralizumab dosing per label

Safety and immunogenicity data collected in extension trials (BORA).

Reslizumab dosing context: Pivotal reslizumab trials used intravenous dosing at 3 mg/kg with demonstrated exacerbation rate reduction and FEV1 improvement; notable safety signals include anaphylaxis and clinically significant creatine phosphokinase elevations.reslizumab 3 mg/kg IV

Reslizumab subgroup analyses in adolescents and select geographic subgroups showed variable results.

Depemokimab dosing context:

Initial therapy considerations (class-level)

Initial therapy considerations (class-level) — laboratory and clinical thresholds historically updated:

Eosinophil threshold history: Policy eosinophil count requirement has been updated multiple times (150 to 300 and back); current policy allows blood eosinophils >=150 cells/mcL for asthma coverage with exceptions when corticosteroids cannot be stopped for testing.>=150 cells/mcL (policy current default)

See agent-specific sections for specificity and age differences.

Exacerbation/FEV1 criteria: Diagnostic criteria include >=2 exacerbations in prior 12 months requiring oral/systemic corticosteroids, or >=1 exacerbation requiring hospitalization/ED/urgent care, or FEV1 <80% predicted; FEV1/FVC <0.80 and worsening on OCS taper are also acceptable options per recent updates.as stated

Added during 2024–2025 updates.

Re-authorization and Continued Therapy

Prior Authorization

Callouts — Provider actions

• Prior authorization is required for all IL‑5 agents covered under this policy. • Renewal (continuation) authorizations may be approved for up to 12 months when documentation shows ongoing clinical benefit.

Prior authorization for IL‑5 agents is required before treatment is provided.
Renewal approval: when criteria for continued therapy are documented, re‑authorization may be granted for up to 12 months.
Follow FDA prescribing information for dosing, administration, and monitoring.
Prescriber and site‑of‑service information must be submitted with the request (prescriber specialty when required by indication, and facility/infusion site if applicable).

Continuation Therapy — evidence of continued benefit

Re‑authorization criteria — covered when ALL of the following are met:

Documentation of ongoing response required: chart notes must demonstrate positive clinical response using one or more of the listed parameters.

Prior Authorization, Documentation, and Prescriber Responsibilities

Prior Authorization

Prior authorization required for initiation and renewal

Prior authorization is required for all agents listed in this policy for initial and re-authorization requests; initial and renewal approvals may be granted up to 12 months when medical necessity criteria and required documentation of response are met.

Prior Authorization

PA applies to IL‑5 HCPCS codes and benefit mapping

Prior authorization applies to the HCPCS codes listed for IL‑5 agents and is managed according to benefit assignment (medical or pharmacy); HCPCS codes include J0517, J2182, J2786, and J3590 (use J3590 to report Exdensur).

Documentation Required

Verify eosinophil counts and background controller therapy

PA requests must verify baseline blood eosinophil results and documentation that the patient is on appropriate background controller therapy with a history of exacerbations or chronic oral steroid use consistent with trial populations.

Billing Codes, Clinical Thresholds, and Key Values

HCPCS codesHCPCS

J0517	Injection, benralizumab (Fasenra) 1 mg
J2182	Injection, mepolizumab (Nucala) 1 mg
J2786	Injection, reslizumab (Cinqair) 1 mg
J3590	Unclassified biologics (use to report: Exdensur)

Historical HCPCS coding updatesHCPCS

J2182	HCPCS code added effective 1/1/17 (policy history reference)
J0517	HCPCS code added effective 1/1/19 (policy history reference)

inv-27: Blood eosinophil count — common threshold for asthma indications and other thresholds noted

Common asthma threshold>=150 cells/mcL (current policy allowance after iterative updates); used as a required blood eosinophil criterion for asthma indications

Higher trial primary analysis>=300 cells/µL (primary analysis group in many pivotal trials such as CALIMA/SIROCCO)

EGPA / HES thresholds noted elsewhere>=1000 cells/microL for EGPA (policy update); HES often uses absolute counts >=1000 cells/microL per Nucala criteria

inv-28: Age thresholds — varies by drug and indication (listed minima by agent)

Exdensur (depemokimab-ulaa)Age >=12 years for asthma indications

Cinqair (reslizumab)

Step Therapy and Prior Treatment Requirements

Requirement	Details
Prior trial of combination LAMA/LABA
Patient must have had a trial of a combination long‑acting muscarinic antagonist (LAMA) plus long‑acting beta‑agonist (LABA) for >=90 days unless the LAMA/LABA product is not tolerated

Consideration	Policy guidance
Demonstrate inadequate control on standard therapies
Policy references alternative and background asthma therapies (e.g., inhaled corticosteroids, LABAs, leukotriene modifiers, methylxanthines, and omalizumab) and requires demonstration of inadequate control on maximal/appropriate controller therapy prior to initiation of an IL‑5 agent

GINA placement	Interpretation for prior authorization
Step 5 add-on therapy
IL‑5 inhibitors are positioned as add‑on treatment in step 5 per GINA 2024 and may be considered after optimization of standard controller therapy

Monotherapy requirement	Policy statement
Monotherapy (no concurrent biologics)
Prior demonstration that the patient meets the policy clinical criteria for use of an IL‑5 inhibitor as monotherapy; combination use with other listed biologics (e.g., Dupixent, Xolair, Tezspire, other IL‑5 agents) is not allowed

Required controller therapy trial	Documentation expected
Inhaled corticosteroid plus long‑acting bronchodilator (and/or leukotriene modifier)
Policy historically required trials/adequate use of inhaled corticosteroids and other controller therapies; current wording requires use of maximum tolerated inhaled corticosteroid plus LABA (and other controllers as appropriate) with documentation of inadequate response prior to approval

Dose and Quantity Limits by Agent

inv-88: Cinqair (reslizumab) — quantity/dose per administration (3 mg/kg)

Cinqair (reslizumab) IV dose3 mg/kg per administration (IV every 4 weeks for asthma indication)

Administration routeIntravenous formulation with dose and site-of-service review for infusion settings

Dose limit referenceDose limit and frequency specified in Cinqair section of policy

inv-89: Exdensur (depemokimab-ulaa) — quantity/dose (100 mg)

Exdensur (depemokimab-ulaa) dose100 mg per administration (subcutaneous), typically every 6 months per policy dosing

Indication age limitApproved coverage criteria reference age >=12 years for asthma indications

Site-of-Service Medical Necessity and Administration Settings

Billing Rule

Preferred administration sites and SOS review (office, infusion center, home, hospital outpatient)

Preferred medically necessary administration sites include physician office, infusion center, home infusion, and hospital‑based outpatient settings; site‑of‑service review applies to these locations and age restrictions (≥13 years) apply to SOS review.

Billing Rule

Infusion center and continuation approvals reference charted response

Drugs addressed by this policy are subject to site‑of‑service review; for continuation approvals reviewers reference chart‑documented clinical response when assessing ongoing medical necessity.

Billing Rule

SOS review applies across hospital outpatient, infusion center, office, and home (age limits apply)

Background and Definitions

Eosinophils are circulating white blood cells that contribute to type 2 inflammatory airway disease by promoting airway inflammation and exacerbations. Interleukin‑5 (IL‑5) is a central cytokine in eosinophil maturation, survival, and recruitment. Monoclonal antibodies that target the IL‑5 pathway reduce eosinophil counts and thereby decrease eosinophil‑driven inflammation. Agents that bind IL‑5 (for example, reslizumab, mepolizumab) neutralize circulating IL‑5, while agents that target the IL‑5 receptor alpha (for example, benralizumab, depemokimab) promote eosinophil apoptosis or depletion. Clinical trials of these IL‑5 pathway inhibitors enrolled patients with an eosinophilic phenotype (commonly defined by baseline blood eosinophil thresholds) and demonstrated reductions in exacerbation rates and, in some populations, improvements in lung function and steroid‑sparing effects.

inv-64: Definition — eosinophil count and role in phenotype identification

Definition of eosinophil countA blood test measuring the quantity of eosinophils (a type of white blood cell) used to identify eosinophilic phenotype

Role in phenotype identificationElevated eosinophil counts (thresholds per policy) guide use of IL-5 inhibitors as add-on therapy for eosinophilic asthma and related conditions

Test types referencedBlood eosinophil count and sputum eosinophil percentage (eg, >=3%) cited as qualifying measures

Policy Changes and Revision Timeline

2026-04-01material_updateLatest

Added coverage criteria for Exdensur (depemokimab-ulaa) and added Exdensur to the list of medications not to be used concurrently with other listed biologics; removed reference to non-formulary exception reviews.

2026-02-01criteria_revision

Allowed blood eosinophil count >=150 cells/mcL for asthma coverage and permitted exceptions when corticosteroids cannot be discontinued for testing; reduced EGPA absolute eosinophil threshold for Fasenra and Nucala from >=1500 to >=1000 cells/microL.

Policy Summary

PayerPremera Bluecross

PolicyIL-5 Inhibitors (Cinqair, Fasenra, Nucala, Exdensur) - Coverage Criteria

Policy CodePolicy N/A

Change TypeAdded and revised coverage criteria (includes new agent)

Effective DateApr 1, 2026

Next Review DateN/A

Key ActionSubmit prior authorization with documentation of eosinophil counts and evidence of uncontrolled disease on maximal controller therapy.

SourceLink

On This Page

SWIFT-1 and SWIFT-2 used depemokimab 100 mg subcutaneous at week 0 and week 26 with pooled reduction in annualized exacerbation rate over 52 weeks; trials enrolled individuals >=12 years with eosinophilic phenotype.

depemokimab 100 mg SQ

Antibody development reported in trials (5–12%); safety extension (AGILE) ongoing.

Required clinical documentation: baseline status and on‑therapy measures sufficient to show improvement or stabilization compared with baseline.

Denial Risk

Denial risk and documentation failures

Denial may result when documentation is insufficient to demonstrate ongoing clinical benefit (for example, no chart notes showing decreased exacerbations, steroid reduction, symptom improvement, or objective measures as relevant to indication). Other potential clinical reasons for denial include lack of prior authorization, absence of required eosinophil or background therapy verification when applicable, or use for an investigational indication.

Documentation Required

Eosinophil and background therapy verification

Providers must verify eosinophil counts and background controller therapy as required by the initial authorization criteria when requesting continuation. For asthma indications, ensure documentation of required prior COPD therapy where applicable and of concurrent inhaled corticosteroid or other background controller use per guideline placement.

Eosinophil verification: provide most recent absolute eosinophil count (timing per indication).
Background therapy verification: document continued use of required controller medications and prior COPD therapy when relevant.

Denial Risk

Concurrent therapy prohibition and investigational exclusions

Concurrent use of multiple biologic agents for asthma is prohibited. Combination therapy with other biologics (including Exdensur) is not allowed; requests for concurrent biologic therapy will be denied. Investigational use of IL‑5 agents for unapproved indications is not covered.

Prohibited concurrent biologics for asthma: co‑administration of two or more asthma biologics is not permitted.
Concurrent therapy prohibition (includes Exdensur): Exdensur and other biologics may not be used in combination with the IL‑5 agent for the same indication.
Investigational use: treatments for investigational or unapproved indications are excluded from coverage.

Documentation Required

Required documentation for renewal requests

When submitting a renewal request include: baseline documentation used for the initial authorization, current chart notes documenting response, most recent labs (eosinophil counts if required), documentation of background controller therapy, prescriber specialty and site‑of‑service, and any objective measures used to assess response (FEV1, nasal polyp size/NCS, exacerbation counts, steroid doses).

Initial authorization documentation: include materials submitted for the original approval.
Chart documentation of response: progress notes showing clinical improvement or stabilization compared with baseline.
Required prior COPD therapy and background controller therapy documentation, when applicable.

Operational alignment and rules for continuation

Operational notes for continuation approvals:

Continuation Therapy — alignment with initial criteria and site‑of‑service rules.

Guideline placement: ensure step‑therapy and prior treatment requirements were met initially and documented for renewal.

Combination therapy exclusion: renewal will not be approved if combination biologic therapy or excluded combinations are present.

Billing Rule

PA plus site‑of‑service medical necessity review may apply

Prior authorization is required for agents in this IL‑5 inhibitor policy and some injection/infusion drugs are subject to site‑of‑service medical necessity review; site‑of‑service rules do not apply to Alaska fully‑insured members per policy.

Prior Authorization

PA criteria updated — thresholds, prescribers, non‑concurrency

Updated prior authorization criteria include new eosinophil thresholds, prescriber requirements for certain agents, and explicit non‑concurrency rules prohibiting combination use with other listed biologics; PA requests must meet these revised criteria.

Step Therapy

Require ≥90‑day LAMA/LABA trial for Nucala in COPD

For Nucala when prescribed for COPD, the patient must have undergone a trial of a combination LAMA/LABA for at least 90 days (unless not tolerated) with continued symptoms and meet the COPD exacerbation criteria before PA will be granted.

Note

Document failure/intolerance of standard controller therapies

The policy references alternative and background asthma therapies (e.g., high‑dose/maximum tolerated ICS, LABAs, leukotriene modifiers, and omalizumab) to show IL‑5 agents are add‑on options after inadequate control on standard therapy.

Step Therapy

Consider IL‑5 agents as step‑5 add‑on per GINA 2024

IL‑5 inhibitors are positioned as add‑on therapy at step 5 in the GINA 2024 guideline sequence; PA decisions should consider guideline‑based sequencing after optimization of standard controller therapy.

Documentation Required

Confirm trials/adequate use of inhaled corticosteroids and controllers

Initial PA historically required documentation of trials or adequate use of inhaled corticosteroids and other controller therapies; policy language was updated from 'maximum doses' to 'maximum tolerated doses' — PA should confirm therapy optimization.

Documentation Required

Provide age, controller therapy status, exacerbation history, and eosinophil results

Initial authorization requests must include the individual's age, confirmation that they are on maximum tolerated inhaled corticosteroid plus a LABA (and other controllers as applicable), history of exacerbations or lung function measures (FEV1/FEV1‑FVC), and blood or sputum eosinophil results where required.

Documentation Required

Include baseline eosinophil counts and prior controller/medication history

PA requests must include baseline blood eosinophil counts, prior use of high‑dose (or maximum tolerated) inhaled corticosteroid plus controller therapy, and a medication history documenting prior exacerbations or chronic oral steroid use to support medical necessity.

Documentation Required

Submit office notes, labs, exam, and medication history

Provide office visit notes with diagnosis, relevant history, laboratory values, physical exam findings, and medication history when submitting PA — incomplete records may lead to denial.

Denial Risk

Do not prescribe concurrently with listed biologics for asthma

Concurrent use of IL‑5 inhibitors with other listed biologics for asthma (including Dupixent, Exdensur, Fasenra, Nucala, Tezspire, and Xolair) is prohibited; requests for combination therapy may be denied.

Denial Risk

Exclude Exdensur from concurrent biologic use

The policy explicitly states concurrent use requests that include Exdensur with other IL‑5 or related biologics may be denied; include Exdensur in non‑concurrency checks when submitting PA.

Denial Risk

Combination therapy with other biologics is not allowed

Combination therapy with other biologics such as Dupixent, omalizumab (Xolair), or tezepelumab is excluded by policy; PA for combination regimens will not be supported.

Documentation Required

Document ongoing clinical response for continued approval

For re‑authorization, providers must document ongoing clinical benefit (e.g., reduced steroid use, fewer exacerbations/ER visits/hospitalizations, symptom reduction, or improved quality of life); lack of documented response may result in denial of continued approval.

Denial Risk

Incomplete documentation may trigger denial

Requests missing required records — office visit notes, diagnosis, relevant history, lab values, physical exam, or medication history — are implied to be not medically necessary and may be denied.

Denial Risk

Uses not outlined in policy are investigational and not covered

Any use of these agents for indications not specified in this policy (all agents listed) is considered investigational and is not covered; do not submit PA for off‑policy indications.

Documentation Required

Include prescriber credentials and site‑of‑service documentation when required

When PA or continuation review applies to some agents, prescriber credentials and site‑of‑service documentation may be required (prescriber requirement added for certain agents and SOS documentation applies where site‑of‑service review is in effect).

Age >=18 years for asthma indications

Fasenra (benralizumab) and Nucala (mepolizumab)Age >=6 years for asthma indications

EGPA and many adult-specific indicationsAge >=18 years (EGPA criteria for Fasenra/Nucala) or as specified per agent

inv-29: NCS scale — nasal congestion score 0-3 used to document CRSwNP response

NCS scale (patient-reported)0 = none

NCS scale1 = mild

NCS scale2 = moderate

NCS scale3 = severe (used to document CRSwNP response)

inv-30: Eosinophil count — subgroup thresholds reported in trials (primary analyses commonly >=300 cells/µL)

Primary trial subgroup cutoff>=300 cells/µL (primary analysis group in pivotal benralizumab and mepolizumab trials)

Common lower threshold in some analyses>=150 cells/µL (observed benefit in some subgroups/post-hoc analyses)

Subgroup breakdowns reportedRanges used in reports: <150, 150-299, 300-449, >450 cells/µL

inv-31: Baseline blood eosinophil count — subgroup cutoffs and notable efficacy thresholds

Reported subgroup cutoffs<150, 150-299, 300-449, >450 cells/µL reported in benralizumab analyses

Notable efficacy threshold>=150 cells/µL shows consistent efficacy signal in several analyses (post-hoc and subgroup)

Primary analysis threshold>=300 cells/µL used as primary analysis in many trials

inv-33: FEV1 criteria — FEV1 <80% predicted or FEV1/FVC <0.80 added in updates as diagnostic/coverage criteria

FEV1 absolute criterionFEV1 <80% predicted (included as an asthma diagnostic/coverage criterion)

FEV1/FVC criterionFEV1/FVC <0.80 (added as alternative diagnostic/coverage criterion)

Use in agent-specific criteriaFEV1 thresholds referenced across Cinqair, Exdensur, Fasenra, and Nucala sections for initiation

inv-34: Blood eosinophil count for asthma coverage — current policy threshold >=150 cells/mcL after iterative changes

Current policy asthma threshold>=150 cells/mcL (policy updated iteratively and currently allows this threshold for asthma coverage)

History of changesThresholds were changed between 150 and 300 cells/mcL across 2024–2025 updates before settling at >=150 cells/mcL

ExceptionsExceptions allowed when individuals cannot discontinue corticosteroids for testing (policy permits use of >=150 despite ongoing steroids)

inv-35: EGPA absolute eosinophil count — updated threshold >=1000 cells/microL for Fasenra and Nucala

EGPA updated absolute eosinophil count>=1000 cells/microL (updated threshold for Fasenra and Nucala EGPA criteria)

Prior thresholdPreviously listed as >=1500 cells/microL before update to >=1000 cells/microL

Additional EGPA requirementsPresence of vasculitic features or ANCA and steroid stability per agent-specific criteria

Administration routeSubcutaneous injection (managed under medical benefit)

inv-90: Fasenra (benralizumab) — quantity/dose (30 mg)

Fasenra (benralizumab) dose30 mg per administration (subcutaneous), maintenance every 8 weeks after initial loading doses

Mechanism noteIL-5 receptor alpha targeting agent that depletes blood eosinophils rapidly

Age indicationPolicy notes age >=6 years for asthma indications

inv-91: Nucala (mepolizumab) — quantity/dose (100 mg typical; 300 mg for EGPA/HES)

Nucala (mepolizumab) typical asthma dose100 mg per administration (subcutaneous) every 4 weeks for asthma, CRSwNP, and COPD indications

Nucala dose for EGPA and HES300 mg per administration every 4 weeks for EGPA and HES indications

Administration and prescriber contextSubcutaneous injection; prescriber requirements and indication-specific criteria apply per policy

inv-92: Quantity limits added per prescribing information for listed agents

Quantity limits addedPolicy added quantity limits per FDA prescribing information for Cinqair, Nucala, and Fasenra

RationaleQuantity limits align dosing and administration frequency with product labeling and site-of-service management

Agents affectedCinqair (reslizumab), Nucala (mepolizumab), Fasenra (benralizumab) specifically noted

inv-93: Quantity limits per prescribing information (historical note)

Historical note on quantity limitsQuantity limits were introduced in prior updates (referenced in 2024 and mid-2024 history notes) per prescribing information

Policy historyHistory entries document addition of dosing limits and non-concurrent biologic restrictions across 2023–2025 reviews

DocumentationSee policy history and 2024 Update for specific effective dates and details

Site‑of‑service medical necessity review applies to hospital outpatient, infusion center, office, and home administration; site‑of‑service rules generally apply for individuals aged 13 years and older and benefit assignment may affect where administration is covered.

Note

Routes vary by agent — reflect SC vs IV in SOS documentation

Administration route differs by agent (subcutaneous for benralizumab and depemokimab; intravenous for reslizumab), and the site‑of‑care policy should reflect approved administration settings when submitting PA.

Billing Rule

SOS medical necessity may apply to injections; Alaska fully‑insured members excepted

Site‑of‑Service medical necessity criteria may be applied to injection drugs; Alaska fully‑insured members are excepted from SOS requirements under Alaska HB 226.

Billing Rule

Added SOS review for Fasenra and Nucala (applies to some agents)

Site‑of‑service review was explicitly added for Fasenra and Nucala and clarified to apply to some injection agents (policy updated to include Fasenra and Nucala SOS review).

inv-65: NCS definition — nasal congestion score used in CRSwNP response measurement

NCS definitionNasal Congestion Score (NCS) is a patient-reported scale used to document improvement in CRSwNP

Scale values0 = none; 1 = mild; 2 = moderate; 3 = severe

Use in continuation decisionsImprovement in NCS plus decrease in nasal polyp size is required to document response for CRSwNP continuation

inv-66: IL-5 inhibitors / IL-5 receptor antagonists — class definition and mechanism

Class definitionIL-5 inhibitors and IL-5 receptor antagonists are monoclonal antibodies that bind IL-5 or the IL-5 receptor to reduce eosinophil production/function

Mechanism examplesAgents acting on circulating IL-5 (mepolizumab, reslizumab) vs IL-5 receptor alpha (benralizumab, depemokimab)

Clinical roleUsed as add-on maintenance therapies to reduce exacerbations in eosinophilic asthma and other eosinophilic conditions

inv-67: Benralizumab (Fasenra) — definition and mechanism

Agent identityBenralizumab (Fasenra) is a monoclonal antibody to the IL-5 receptor alpha

MechanismBinds IL-5Rα on eosinophils and basophils leading to cell death and near-complete blood eosinophil depletion

Clinical contextUsed as add-on maintenance therapy for severe eosinophilic asthma; dosing and age criteria in policy

inv-68: Reslizumab (Cinqair) — brief agent definition

Reslizumab identityReslizumab (Cinqair) is a humanized monoclonal antibody that binds circulating IL-5 to reduce eosinophilia

AdministrationIntravenous formulation managed under medical benefit with dosing at 3 mg/kg

Clinical noteUsed as add-on maintenance therapy for severe eosinophilic asthma per policy criteria

inv-69: Depemokimab (Exdensur) — brief agent definition

Depemokimab identityDepemokimab (Exdensur) is an IL-5 antagonist monoclonal antibody that binds the IL-5 receptor complex to reduce eosinophils

Dosing summaryPolicy dosing: 100 mg subcutaneous with coverage criteria for patients >=12 years

Indication contextAdded to policy as a covered IL-5 agent with prohibitions on concurrent biologics

inv-70: Therapeutic class summary — IL-5 inhibitors placement (GINA step 5)

Therapeutic class placementIL-5 inhibitors are positioned as add-on therapy in step 5 of GINA 2024 asthma guidelines

Clinical roleUsed when patients remain uncontrolled on optimized standard controller therapies

Policy alignmentPolicy references guideline placement when specifying sequencing and background therapy requirements

inv-71: Standard controller therapies — list referenced in appendix and policy context

Standard controller therapies (ICS)Inhaled corticosteroids (listed agents in appendix such as fluticasone, budesonide, mometasone)

Long-acting bronchodilatorsLong-acting bronchodilators and combination ICS/LABA products are referenced as standard controllers (eg, salmeterol-containing combos, Breo, Dulera, Symbicort)

Role in policyDocumentation of use of maximum tolerated doses of inhaled corticosteroid plus LABA is required for IL-5 agent initiation per policy

site_of_service_addition

Added site-of-service review for Fasenra and Nucala and clarified site-of-service medical necessity criteria can apply to injection drugs (effective Oct 3, 2025 following provider notification).

2024-10-01eosinophil_threshold_change

Interim update changed asthma eosinophil requirement from 150 cells/mcL to 300 cells/mcL then later restored to 150 cells/mcL in subsequent updates and added prescriber requirements for several agents.

2026-04-01effective_dateLatest

Policy effective date: 2026-04-01 (Annual Review approved March 10, 2026).

2026-03-10review_date

Last review: March 10, 2026 (Annual Review approved; changes include addition of Exdensur and concurrent-use updates).

2026-01-13interim_review

Interim Review approved January 13, 2026 updated asthma management to allow oral/systemic corticosteroids for exacerbations and eosinophil threshold adjustments for asthma and EGPA.