ModifiedAnthemPolicy CC-0247

Beyfortus (nirsevimab)

Clinical criteria, quantity limits, override rules, coding, and administrative guidance for medical-benefit coverage of Beyfortus (nirsevimab) for prevention of RSV lower respiratory tract disease in infants and pediatric individuals up to 24 months entering first or second RSV season.

Policy Summary

PayerAnthem

PolicyBeyfortus (nirsevimab)

Policy CodePolicy CC-0247

Change TypeAnnual review - coding and exclusions updated

Effective Date

Next Review Date

Key ActionPrior authorization/clinical review required; approve only when all applicable clinical criteria (age, season, risk factors) are met and exclusions are absent.

SourceLink

POLICY UPDATE CHANGES

Added Enflonsia into the may not be used in combination criteria.

Updated criteria references and coding descriptions for CPT 90380, 90381, 96380, 96381; removed ICD10-CM Z23 and added multiple ICD-10 ranges.

Annual review prior updates: removed criteria to address maternal RSV vaccination (8/16/2024) and earlier changes to approval duration and CPT additions in 2023.

2Seasons addressed (first and second)

5Second-season high-risk categories listed

1Dose override circumstance

4CPT/Administration codes listed

Coverage Summary

Scope: This policy covers medical-benefit use of Beyfortus (nirsevimab-alip) for prevention of RSV lower respiratory tract disease in neonates and infants born during or entering their first RSV season (<8 months of age) and in select children entering their second RSV season (8–19 months) with documented high-risk conditions. Coverage is defined by clinical criteria, quantity limits, override rules, coding and administrative guidance specifying dosing by weight and season and limiting approval to the RSV surveillance-defined season (commonly October through March).

Coverage stance: Beyfortus is covered with criteria (covered_with_criteria) when used for prophylaxis per ACIP (2023) recommendations and AAP guidance (2024, updated 2025) that align with ACIP and state that Beyfortus is preferred over palivizumab for routine RSV prophylaxis. Approvals follow age- and risk-based criteria (first-season: <8 months, weight-based 50 mg or 100 mg dosing; second-season: 8–19 months with specified high-risk conditions) and are limited to the CDC/NREVSS-defined RSV season.

Initial Therapy Criteria (First RSV Season)

Approval Criteria for Beyfortus (nirsevimab) — Initial Therapy (First RSV season)

ALL of the following

Individual is using Beyfortus (nirsevimab) for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease.
Individual is less than 8 months of age.
Individual has not previously received a dose of Beyfortus (nirsevimab).
Per ACIP guidance: one dose recommended for infants aged <8 months entering or born during their first RSV season.
Not approvable if
- Individual is being treated for active RSV disease.
- Individual has received five doses or more of Synagis (palivizumab) during the same RSV season.
- Individual has received Enflonsia (clesrovimab-cfor) during the same RSV season.

Prior Authorization

Prior Authorization Required

Prior authorization required. Submit clinical documentation demonstrating age and prior Beyfortus receipt status. Requests that meet denial conditions (treatment of RSV or receipt of disallowed agents during the same RSV season) will not be approved.

Affected codes: CPT 90380, CPT 90381, CPT 96380, CPT 96381

Billing Rule

Quantity Limits / Billing Rule

Per-weight dosing and quantity limits for first RSV season. For initial (first season) dosing: administer one 50 mg syringe if the infant weighs less than 5 kg, or one 100 mg syringe if the infant weighs 5 kg or greater. Quantity limits restrict one syringe per patient for the first RSV season except as noted in override criteria (e.g., cardiopulmonary bypass).

50 mg/0.5 mL syringe — one syringe, one time only (for infants <5 kg)
100 mg/mL syringe — one syringe during first RSV season (for infants ≥5 kg); second season dosing differs
Quantity limit notes: First RSV season = one syringe per season; override criteria permit an additional dose surrounding cardiopulmonary bypass as specified in policy

Continuation / Second-Season Criteria

Approval Criteria for Beyfortus (nirsevimab) — Second RSV season (and Either path)

Requests for Beyfortus (nirsevimab) may be approved if the following criteria are met:

Either

First RSV season eligibility: Individual is less than 8 months of age and has not previously received a dose of Beyfortus (ACIP)< 8 months
Second RSV season eligibility
- AND meets one of the following
  - Preterm with ongoing oxygen requirement: Preterm infant born at less than 32 weeks, 0 days gestation who required at least 28 days of oxygen after birth AND continues to require medical intervention within 6 months of the start of the second RSV season (including supplemental oxygen, chronic corticosteroid therapy or diuretics)

Exclusions / Not Approved

Requests for Beyfortus (nirsevimab) may not be approved for the following:

Treatment of RSV disease
>=5 doses of palivizumab: Individual has received five doses or more of Synagis (palivizumab) during the same RSV season>= 5 doses
Enflonsia same season: Individual has received Enflonsia (clesrovimab-cfor) during the same RSV season
Added 8/15/2025
Not approved when criteria unmet:

Applicable Codes

Beyfortus product HCPCS/CPT (informational)CPT|HCPCS

90380	Respiratory syncytial virus, monoclonal antibody, seasonal dose; 0.5 mL dosage, for intramuscular use [Beyfortus]
90381	Respiratory syncytial virus, monoclonal antibody, seasonal dose; 1 mL dosage, for intramuscular use [Beyfortus]
96380	Administration of respiratory syncytial virus, monoclonal antibody, seasonal dose by intramuscular injection, with counseling by physician or other qualified health care professional [when specified as injection of Beyfortus (nirsevimab-alip)]
96381	Administration of respiratory syncytial virus, monoclonal antibody, seasonal dose by intramuscular injection [when specified as injection of Beyfortus (nirsevimab-alip)]

ICD-10 Diagnosis codes referenced (informational)ICD-10

D81.0-D81.9	Combined immunodeficiencies
E84.0-E84.9	Cystic fibrosis
P07.20-P07.26	Extreme immaturity of newborn [less than 28 completed weeks of gestation]
P07.30-P07.35	Preterm newborn [28 completed weeks or more but less than 32 completed weeks of gestation]
Z29.11	Encounter for prophylactic immunotherapy for respiratory syncytial virus (RSV)
Z94.0-Z94.9	Transplanted organ and tissue status

Billing Rule

Approval duration and seasonal timing

Approval is limited to the RSV season as determined by CDC/NREVSS surveillance or local health departments; the policy notes the typical months October through March. Approval generally covers one dose per season.

Season determined by CDC/NREVSS or local health department
Typical window: October through March
One dose may be approved during the season

Provider Actions & Administrative Rules

Prior Authorization

Prior authorization checklist

Prior authorization/clinical review is required before coverage. Expected checklist for review: confirm patient age for first or second season, verify current RSV season timing, document applicable high-risk factors, and confirm no exclusions (treatment of active RSV, ≥5 doses palivizumab this season, or receipt of Enflonsia this season).

Age: <8 months (first season) or 8–19 months entering second season
Season: within CDC/NREVSS or local health department–defined RSV season (typically Oct–Mar)
Risk factors documented per second-season criteria
Exclusions absent: treatment of RSV, ≥5 Synagis doses this season, no Enflonsia this season

Documentation Required

Documentation examples for second-season eligibility

Clinical Evidence & Guideline Alignment

Evidence summary: Guideline alignment is with ACIP (2023) and AAP guidance (2024, updated 2025) supporting nirsevimab for first- and second-season prophylaxis and stating a preference for Beyfortus over palivizumab based on efficacy, duration, and convenience.

Key clinical trial references supporting the policy include NEJM reports of single-dose nirsevimab efficacy in preterm infants (2020) and in healthy late-preterm and term infants (2022), as well as 2022 safety data in infants with heart or lung disease or prematurity; these are cited as principal clinical evidence for effectiveness and safety.

Background & Definitions

Background: Beyfortus (nirsevimab-alip) is an FDA-approved monoclonal antibody directed at the RSV F protein for prevention of RSV lower respiratory tract disease in neonates and infants during their first RSV season and in selected high-risk children entering a second RSV season. ACIP issued recommendations in 2023 and the AAP guidance (2024, updated 2025) aligns with ACIP and explicitly prefers Beyfortus over palivizumab (Synagis) because of its efficacy, longer duration, and convenience.

Seasonal timing: Use and approvals are intended to occur shortly before or during the RSV season as defined by CDC surveillance (NREVSS), with one dose typically approved during the months noted for the approval window (commonly October through March).

Term	Definition
RSV season
Seasonal period as determined by CDC surveillance (NREVSS) or local health department; months October through March noted for approval window.
Second RSV season
The RSV season following an individual's first season; eligibility limited to ages 8-19 months with documented high-risk conditions (including chronic lung disease of prematurity with recent medical support, severe immunocompromise, cystic fibrosis with severe lung disease or weight-for-length <10th percentile, and American Indian or Alaska Native children).

Revision History

8/15/2025material_changeLatest

Added Enflonsia (clesrovimab-cfor) into the 'may not be used in combination' / exclusion criteria.

8/15/2025coding_updateLatest

Coding reviewed: updated descriptions for CPT 90380, 90381, 96380, 96381; removed ICD‑10‑CM Z23 and added ICD‑10‑CM D81.0‑D81.9, E84.0‑E84.9, P07.20‑P07.26, P07.30‑P07.35, Z94.0‑Z94.9.

8/16/2024policy_revision

Policy Summary

PayerAnthem

PolicyBeyfortus (nirsevimab)

Policy CodePolicy CC-0247

Change TypeAnnual review - coding and exclusions updated

Effective Date

Next Review Date

Key ActionPrior authorization/clinical review required; approve only when all applicable clinical criteria (age, season, risk factors) are met and exclusions are absent.

SourceLink

On This Page

gestation < 32 wks; oxygen >= 28 days; ongoing intervention within 6 months

Cystic fibrosis severe disease or low weight-for-length: Cystic fibrosis with severe lung disease (history of hospitalization for pulmonary exacerbation in the first year of life or abnormalities on chest imaging that persist when stable) OR weight-for-length less than tenth percentileweight-for-length < 10th percentile

Profound immunocompromise: Profoundly immunocompromised (including severe combined immunodeficiency, advanced acquired immunodeficiency syndrome, undergoing organ or hematopoietic stem cell transplant, or an absolute lymphocyte count of less than 100 cells/mm3)absolute lymphocyte count < 100 cells/mm3

American Indian: Individual is an American Indian

Alaska Native: Individual is an Alaska Native

Root: Individual is using for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease

Documentation Required

Document risk factors for second season

Provide documentation for second-season eligibility showing the applicable high-risk condition(s). Required documentation items include evidence of prematurity, ongoing medical interventions within 6 months of season start, cystic fibrosis severity or weight-for-length <10th percentile, transplant or profound immunocompromise, or American Indian/Alaska Native status.

Prematurity (<32 wks 0 days gestation with ≥28 days oxygen after birth)
Ongoing medical interventions within 6 months of season start (supplemental oxygen, chronic corticosteroid therapy, or diuretics)
Cystic fibrosis with severe lung disease or weight-for-length <10th percentile
Transplant / profoundly immunocompromised (e.g., combined immunodeficiency, AIDs, transplant, ALC <100 cells/mm3)
American Indian or Alaska Native status

Prior Authorization

Cardiopulmonary bypass surgery override

One additional dose may be approved for individuals undergoing cardiac surgery with cardiopulmonary bypass. Timing rules: First season — if surgery is within 90 days of prior Beyfortus, may approve an additional dose based on current weight (one 50 mg syringe if <5 kg or one 100 mg syringe if ≥5 kg); if surgery is >90 days after prior dose, may approve one 50 mg syringe. Second season — if surgery is within 90 days of prior Beyfortus, may approve two 100 mg syringes.

May not be approved when the above criteria are not met and for all indications

Denial Risk

Denial conditions for same-season treatments

Requests may be denied when Beyfortus is being used to treat active RSV disease, if the patient received five or more doses of palivizumab (Synagis) in the same RSV season, or if the patient received Enflonsia (clesrovimab-cfor) during the same RSV season.

Treatment of active RSV disease
Received ≥5 doses of palivizumab (Synagis) during the same RSV season
Received Enflonsia (clesrovimab-cfor) during the same RSV season

Document second-season qualifying conditions with supporting records. Examples of acceptable documentation include birth records showing gestational age and oxygen requirement, medical notes or prescriptions reflecting ongoing supplemental oxygen or corticosteroid/diuretic therapy within 6 months of season start, hospitalization or chest imaging reports for cystic fibrosis severity, transplant or immunology records, or documentation of American Indian/Alaska Native status.

Birth record for gestational age and duration of oxygen after birth
Medical records showing supplemental oxygen, chronic corticosteroid therapy, or diuretic use within 6 months
Hospitalization records or chest imaging for cystic fibrosis severe lung disease or growth charts showing weight-for-length <10th percentile
Transplant/ immunodeficiency documentation or absolute lymphocyte count <100 cells/mm3
Documentation of American Indian or Alaska Native status

Billing Rule

Dose quantity limits and time windows

Quantity-limit details and dosing per season: First season — one 50 mg syringe if <5 kg (one-time only) or one 100 mg syringe if ≥5 kg. Second season — two 100 mg syringes (quantity limit: two syringes per 6 months).

50 mg: one syringe, one time (first season only)
100 mg: one syringe (first season if ≥5 kg); two 100 mg syringes allowed in second season (two syringes per 6 months)

Prior Authorization

CPB surgery additional-dose override criteria

For cardiopulmonary bypass surgery, an exception may be approved with timing- and dose-specific criteria. Criteria: surgery during RSV season and perioperative need. Timing rules — First season: if surgery is within 90 days of a prior Beyfortus dose, one additional dose may be approved based on current weight (50 mg if <5 kg or 100 mg if ≥5 kg); if surgery is >90 days after prior dose, may approve one 50 mg syringe. Second season: if surgery is within 90 days of prior Beyfortus, may approve two 100 mg syringes.

Applies to individuals undergoing cardiac surgery with cardiopulmonary bypass
First season: within 90 days → additional dose by current weight; >90 days → one 50 mg syringe
Second season: within 90 days → may approve two 100 mg syringes

Annual review: removed criteria addressing maternal RSV vaccination; wording and formatting changes; coding reviewed with no changes.

11/17/2023policy_revision

Select review: removed 'may not approve' criterion for prior RSV infection; added quantity limit override criteria for cardiopulmonary bypass; coding reviewed; effective 10/6/2023 removed CPT 96372 and added CPTs 96380, 96381.

10/2/2023policy_revision

Select review: updated criteria to address maternal RSV vaccination and approval duration language; coding reviewed and added CPTs 90380, 90381, 96372 and ICD‑10‑CM Z23, Z29.11; removed HCPCS J3490, J3590, J9999, C9399.

8/18/2023policy_creation

Annual review / new clinical criteria and quantity limit for Beyfortus; coding reviewed and added HCPCS J3490, J3590, J9999, C9399.