CurrentNeighborhood Health Plan of Rhode IslandPolicy N/A

Orladeyo (berotralstat) for prophylaxis of hereditary angioedema

Policy governs coverage and approval criteria for berotralstat (Orladeyo) as prophylactic therapy to prevent hereditary angioedema (HAE) attacks for Medicaid members aged 12 years and older.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyOrladeyo (berotralstat) for prophylaxis of hereditary angioedema

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateMay 1, 2021

Next Review DateN/A

Key ActionObtain prior authorization for Orladeyo with documentation of HAE type I/II and lab or genetic confirmation; approvals are for 6 months.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

12+minimum patient age for coverage

6 moauthorization duration

150 mg/daymaximum daily dose

1 cap/daydispensing limit

Coverage Criteria for Orladeyo (berotralstat)

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Initial Approval - Overall: Member is >= 12 years of age.

Diagnosis and confirmation: Member has a documented diagnosis of hereditary angioedema (HAE) type I or type II.

Prescriber specialty: Medication is prescribed by, or in consultation with, an allergist/immunologist or a physician who specializes in the treatment of HAE or related disorders.

Laboratory or genetic confirmation (one of)

C1-INH deficiency/dysfunction - functional low: Normal C1‑INH antigenic level with low C1‑INH functional level (functional C1‑INH < 50% or below the laboratory lower limit of normal).
C1-INH antigenic low: C1‑INH antigenic level is below the lower limit of normal as defined by the testing laboratory.
Genetic or clinical criteria when C1-INH testing normal: Normal C1‑INH antigenic and functional levels with either: documented pathogenic mutation consistent with HAE (e.g., F12, ANGPT1, PLG, KNG1, HS3ST6, MYOF) OR family history of angioedema refractory to a trial of high‑dose antihistamine (at least one month).

Rule out other causes: Other causes of angioedema have been ruled out (e.g., ACE‑inhibitor induced angioedema, estrogen‑related angioedema, allergic angioedema).

Dose limit: Requested dose does not exceed one Orladeyo 150 mg capsule per day (150 mg/day).<= 150 mg/day

Concomitant therapy exclusion: Will not be used in combination with Andembry, Cinryze, Takhzyro, or Haegarda (C1‑INH replacement or related prophylactic agents).

Indication for prophylaxis (one of): Patient is receiving treatment as short‑term HAE prophylaxis for a procedure OR is receiving long‑term prophylaxis because on‑demand therapies did not provide satisfactory control or access is limited, AND the patient meets long‑term prophylaxis criteria such as debilitating cutaneous or gastrointestinal episodes, history of at least one laryngeal attack, or >5 disabling HAE days per month.

inv-02: Continuation of Therapy

Authorization of 6 months may be granted for continuation when ALL of the following are met:

Continuation - Overall: Member continues to meet all criteria for initial approval (as defined in the Initial Approval criteria).

Clinical response: Documentation of a favorable clinical response since initiating Orladeyo prophylactic therapy (for example, decreased frequency, severity, or duration of HAE acute attacks compared with baseline).

Reduced acute medication use: Documentation of reduced use of medications to treat acute HAE attacks since starting Orladeyo.

Provider Actions and Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for Orladeyo (berotralstat) for prophylaxis of hereditary angioedema (HAE). When initial criteria are met, approval may be granted for up to 6 months for members aged 12 years and older.

Initial approval duration: up to 6 months
Required prescriber: prescribed by or in consultation with an allergist/immunologist or a physician who specializes in HAE or related disorders

Step Therapy

On‑demand Therapy Considerations

A trial of on‑demand therapies is required prior to approval for long‑term prophylaxis, or documentation that on‑demand therapy is inappropriate or not accessible. On‑demand options include icatibant, ecallantide, and plasma‑derived or recombinant C1‑INH products (e.g., Berinert, Ruconest). If on‑demand therapy was tried but did not provide satisfactory control, or access is limited, document the reason and clinical response.

Document trial and response to on‑demand agents (e.g., icatibant, ecallantide, Berinert, Ruconest) OR documentation that on‑demand therapy is inappropriate or inaccessible
If on‑demand failed, provide details of lack of satisfactory control or access barriers

Documentation Required

Required Clinical Documentation

Required clinical documentation must be submitted with the prior authorization request. This should include diagnostic and laboratory confirmation of HAE and treatment rationale.

Diagnosis of HAE type I or II documented in the medical record
Laboratory confirmation of C1‑INH deficiency or dysfunction (low C1‑INH functional level <50% or below laboratory lower limit of normal, or low C1‑INH antigenic level below laboratory lower limit)
If C1‑INH antigenic level is normal with low function, include functional assay result; if C1‑INH is normal, provide supporting family history and genetic testing if available (e.g., F12, ANGPT1, PLG, KNG1, HS3ST6, MYOF)
Documentation that other causes of angioedema have been ruled out (e.g., ACE‑inhibitor–induced angioedema, allergic causes, estrogen‑related angioedema)
Clinical history supporting need for long‑term prophylaxis (e.g., recurrent debilitating cutaneous or gastrointestinal episodes, history of at least one laryngeal attack, or ≥5 HAE‑related disability days per month)
Statement that Orladeyo will not be used in combination with other prophylactic C1‑INH products (e.g., Cinryze, Haegarda, Takhzyro/lanadelumab, Andembry)

Denial Risk

Excluded Indications

Orladeyo is not indicated for treatment of acute HAE attacks and use for acute treatment or other non‑prophylactic indications is considered experimental/investigational and not medically necessary.

Excluded: treatment of acute HAE attacks
All other non‑prophylactic indications are experimental/investigational and not medically necessary

Background on Hereditary Angioedema and Orladeyo

Hereditary angioedema (HAE) is a disorder caused by deficiency or dysfunction of the C1 inhibitor, which leads to recurrent episodes of angioedema. Orladeyo (berotralstat) is an oral, once-daily medication approved for the prevention (prophylaxis) of HAE attacks in appropriately selected patients; it is not for treatment of acute HAE attacks.

Definitions and Diagnostic Criteria

C1-INH functional deficiency

DefinitionLaboratory finding of low C1 inhibitor functional level (functional C1-INH less than 50% or below the laboratory lower limit of normal)

Antigenic level statusMay occur with normal or low antigenic C1-INH level (normal antigenic level with low function also supports diagnosis)

UseUsed to confirm HAE type I or II when documented by laboratory testing

Long-term prophylaxis criteria

Long-term prophylaxis criteria (summary)History of debilitating cutaneous or gastrointestinal episodes, at least one laryngeal attack, or more than 5 disabling HAE days per month

Alternative confirmationsDiagnosis of HAE type I or II supported by laboratory or genetic testing or family history with refractory symptoms

Prescriber requirementMedication prescribed by or in consultation with an allergist/immunologist or HAE specialist