CurrentColorado Rocky Mountain Health PlansPolicy N/A

Orladeyo (berotralstat) prior authorization for hereditary angioedema prophylaxis

Defines prior authorization and medical necessity criteria for coverage of Orladeyo (berotralstat) for prophylaxis of hereditary angioedema (HAE) in Colorado Rocky Mountain Health Plans members; applies to prescribers (immunologists, allergists) and pharmacy/medical benefit reviewers.

Policy Summary

PayerColorado Rocky Mountain Health Plans

PolicyOrladeyo (berotralstat) prior authorization for hereditary angioedema prophylaxis

Policy CodePolicy N/A

Change TypeMaterial: age-stratified prior-failure updatesaddition of Andembrydiagnostic clarifications

Effective DateApr 1, 2026

Next Review DateN/A

Key ActionObtain and document age-specific prior therapy failure history (including dates and reasons) per the defined age bands before requesting prior authorization.

SourceLink

POLICY UPDATE CHANGES

Updated coverage criteria based on updated FDA indication by separating tried/failed therapies based on age limitations for Haegarda and Andembry.

Andembry (garadacimab) was added to the list of required preventive HAE agents.

Diagnostic criteria for HAE with normal C1 inhibitor levels were updated.

12 monthsauthorization duration

>=2 yrsminimum approved age

3 bandsage-based pathways

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Coverage Criteria for Orladeyo (berotralstat)

Initial Therapy

Covered when ALL of the following are met

Initial approval: Member has a diagnosis of hereditary angioedema (HAE) confirmed by either: (A) C1 inhibitor (C1-INH) deficiency or dysfunction (Type I or II HAE) documented by C1-INH antigenic level below the lower limit of normal or C1-INH functional level below the lower limit of normal, OR (B) HAE with normal C1-INH as evidenced by a confirmed pathogenic variant in one of the specified genes (factor XII, angiopoietin-1, plasminogen-1, kininogen-1, myoferlin, HS3ST6) OR recurring angioedema refractory to high-dose antihistamines with confirmed family history or de-novo mutation)

based on diagnostic pathways

Indication: Prescribed for prophylaxis to prevent HAE attacks (not for treatment of acute HAE attacks)

No concomitant prophylaxis: Not used in combination with other approved products indicated for prophylaxis against HAE attacks (Andembry, Cinryze, Dawnzera, Haegarda, Takhzyro)

Prescriber specialty: Prescribed by an immunologist or an allergist

Age-specific prior therapy failures

Age 2 to <6 years: Patient is ≥ 2 years and < 6 years AND history of failure to Takhzyro (lanadelumab)
document date of trial and reason for failure
Age 6 to <12 years: Patient is ≥ 6 years and < 12 years AND history of failure to both Haegarda (C1 esterase inhibitor, human) AND Takhzyro (lanadelumab)
document date of trial and reason for failure for each agent
Age ≥12 years: Patient is ≥ 12 years AND history of failure to Andembry (garadacimab), Haegarda (C1 esterase inhibitor, human), AND Takhzyro (lanadelumab)
document date of trial and reason for failure for each agent

title": "Initial Therapy"

Coverage of Orladeyo (berotralstat) is limited to use as prophylaxis to prevent hereditary angioedema (HAE) attacks and it is not indicated for treatment of acute HAE attacks. Requests for Orladeyo that document concurrent use with other approved prophylactic HAE agents (e.g., Andembry, Cinryze, Dawnzera, Haegarda, Takhzyro) will not meet coverage criteria because the agent must not be used in combination with other prophylactic HAE products. Prescribers must attest that the member has experienced attacks of sufficient severity or frequency to warrant prophylactic therapy. Authorization, when approved, is issued for 12 months.

Orladeyo will be considered not medically necessary when it is prescribed in combination with other prophylactic HAE products or when required documentation of prior therapeutic failures (per the age‑based step therapy requirements) is not provided. The policy requires documentation of dates and reasons for prior trials and failures of the specified agents; absence of that documentation will result in denial of the request. Additionally, Orladeyo is typically excluded from coverage unless the member meets the stated criteria or coverage is mandated by law or the benefit plan.

Coding and Age-band Summary

No explicit codes listedmixed

No codes listed

Age bands for step therapy

Age band: 2 to <6 yearsApplies to patients >=2 and <6 years; requires documented history of failure to Takhzyro (lanadelumab) with dates and reason for therapeutic failure

Age band: 6 to <12 yearsApplies to patients >=6 and <12 years; requires documented history of failure to both Haegarda (C1 esterase inhibitor, human) and Takhzyro (lanadelumab) with dates and reasons for therapeutic failure

Age band: >=12 yearsApplies to patients >=12 years; requires documented history of failure to Andembry (garadacimab), Haegarda, and Takhzyro with dates and reasons for therapeutic failure

Minimum approved age for considerationMember must be at least 2 years of age to meet step-therapy paths

Prior Authorization & Provider Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for Orladeyo (berotralstat) for prophylaxis of hereditary angioedema (HAE). Requests must document diagnosis, indication (prophylaxis), prior-failure therapy per age-based step requirements, and that Orladeyo will not be used in combination with other HAE prophylactic agents. Authorization will be issued for 12 months.

Affected products: Orladeyo (berotralstat)
Do not combine with: Andembry, Cinryze, Dawnzera, Haegarda, Takhzyro
Authorization duration: 12 months

Denial Risk

Combination Therapy and Prior-Failure Requirements

Orladeyo is approved only for prophylaxis of HAE attacks and must not be prescribed in combination with other approved prophylactic HAE agents. If combination therapy is documented, approval will be denied unless the member has documented failure of the listed agents per the age-stratified step therapy below.

Background

Orladeyo (berotralstat) is an oral plasma kallikrein inhibitor indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in patients aged 2 years and older. It is not indicated for the treatment of acute HAE attacks; use is intended to reduce the frequency and/or severity of attacks when prophylactic therapy is clinically warranted.

Definitions of Hereditary Angioedema Types

Type I/II HAE (C1-INH deficiency/dysfunction)

DefinitionType I or II hereditary angioedema (HAE) due to C1 inhibitor (C1-INH) deficiency or dysfunction diagnosed by laboratory evidence of either a C1-INH antigenic level below the lower limit of normal or a C1-INH functional level below the lower limit of normal

Clinical implicationDiagnostic confirmation by lab report is required for prior authorization

Example lab findingsC1-INH antigenic or functional level reported below the laboratory’s lower limit of normal

HAE with normal C1‑INH

DefinitionHereditary angioedema (HAE) with normal C1-INH diagnosed by either: confirmed presence of pathogenic variant(s) in specified genes (factor XII, angiopoietin-1, plasminogen-1, kininogen-1, myoferlin, HS3ST6) or recurrent angioedema refractory to high‑dose antihistamines with a confirmed family history or with suspected de‑novo mutation

Revision History & Material Changes

2026-01-01revisedLatest

Coverage criteria revised to separate required prior-failure therapies by age bands (2-<6, 6-<12, >=12) reflecting updated FDA indications for Haegarda and Andembry.

2025-11-01added

Andembry (garadacimab) was added to the list of required preventive HAE agents and to examples of prophylactic HAE drugs.

2024-03-01clarified