ModifiedUnitedHealthcarePolicy CS2025D0085M

Adakveo (crizanlizumab-tmca) — Medical Benefit Drug Policy

Medical benefit drug policy governing use of Adakveo for reduction of vaso-occlusive crises in patients with sickle cell disease for UnitedHealthcare Community Plan; defines initial and continuation criteria, coding, and exclusions.

Policy Summary

PayerUnitedHealthcare

PolicyAdakveo (crizanlizumab-tmca) — Medical Benefit Drug Policy

Policy CodePolicy CS2025D0085M

Change TypeCoverage criteria revised; attestation alternative added

Effective DateJune 1, 2025

Next Review DateN/A

Key ActionSubmit prior authorization with provider attestation if the patient is not an appropriate candidate for hydroxyurea based on genotype, and include documentation of VOC history or hydroxyurea intolerance/use as applicable.

SourceLink

POLICY UPDATE CHANGES

Revised coverage criteria; added criterion to allow coverage when the provider attests that the patient is not an appropriate candidate for hydroxyurea based on the patient's genotype (i.e., the patient does not have homozygous hemoglobin SS (HbSS) or sickle beta0 thalassemia).

Added language to indicate this Medical Benefit Drug Policy does not apply to the state of Arizona; refer to the state's Medicaid clinical policy.

Updated References section to reflect the most current information; archived previous policy version CS2025D0085L.

16 yrsminimum age for coverage

≥2min VOCs in prior 12 months

12 momax initial auth

<16explicit noncoverage

CS2025D0085Larchived prior version

Coverage Criteria for Adakveo (crizanlizumab-tmca)

Initial Therapy

Covered when ALL of the following are met

Age: Patient is 16 years of age or older

Diagnosis of a sickle cell disease (including but not limited to homozygous hemoglobin S (HbSS), sickle hemoglobin C disease (HbSC), sickle beta0 thalassemia, and sickle beta+ thalassemia)

Prior VOCs or transition: Either patient is transitioning from treatment with Oxbryta (voxelotor) to Adakveo OR patient has previously experienced 2 or more sickle cell-related vasoocclusive crises within the previous 12 months

Hydroxyurea status: Either patient is currently receiving hydroxyurea therapy OR has history of treatment failure, intolerance, or contraindication to hydroxyurea OR provider attests that the patient is not an appropriate candidate for hydroxyurea based on the patient’s genotype (i.e., the patient does not have homozygous hemoglobin SS (HbSS) or sickle beta0 thalassemia)

Concomitant therapy exclusions: Patient is not receiving concomitant chronic, prophylactic blood transfusion therapy AND is not receiving concomitant Oxbryta (voxelotor) therapy

Prescriber and dosing: Adakveo is prescribed by, or in consultation with, a hematologist or other specialist with expertise in the diagnosis and management of sickle cell disease AND initial dosing is in accordance with the United States Food and Drug Administration approved labeling

Authorization length: Initial authorization will be for no more than 12 months

Continuation Therapy

Covered when ALL of the following are met

Diagnosis of a sickle cell disease (including but not limited to homozygous hemoglobin S (HbSS), sickle hemoglobin C disease (HbSC), sickle beta0 thalassemia, and sickle beta+ thalassemia)

Clinical response: Patient has experienced a reduction in sickle cell-related vasoocclusive crises and/or a decrease in severity of sickle cell-related vasoocclusive crises from pretreatment baseline while on Adakveo

Concomitant therapy exclusions: Patient is not receiving concomitant chronic, prophylactic blood transfusion therapy AND is not receiving concomitant Oxbryta (voxelotor) therapy

Prescriber and dosing: Adakveo is prescribed by, or in consultation with, a hematologist or other specialist with expertise in the diagnosis and management of sickle cell disease AND maintenance dosing is in accordance with the United States Food and Drug Administration approved labeling

Not Medically Necessary / Exclusions

Explicit non-covered indications: Adakveo is not proven or medically necessary for pediatric patients less than 16 years of age with sickle cell disease OR for myelofibrosis

Revised Coverage Rationale (attestation alternative)

Policy was revised to allow coverage when a provider attests patient is not an appropriate candidate for hydroxyurea based on genotype.

Coverage when provider attests: Provider attests the patient is not an appropriate candidate for hydroxyurea based on genotype (i.e., the patient does not have homozygous hemoglobin SS (HbSS) or sickle beta0 thalassemia).

This is an added criterion to the coverage rationale.

Adakveo (crizanlizumab-tmca) is not proven or medically necessary for the treatment of pediatric patients younger than 16 years of age with sickle cell disease. The policy also explicitly excludes use of Adakveo for the treatment of myelofibrosis.

This Medical Benefit Drug Policy does not apply to the state of Arizona. For members in Arizona, consult the state Medicaid clinical policy for applicable coverage rules and requirements before authorizing Adakveo.

Adakveo is considered not medically necessary for pediatric patients under 16 years of age because safety and efficacy have not been established in this age group. Documentation supporting medical necessity for patients under 16 is not consistent with the policy and may lead to denial.

The FDA-approved indication for Adakveo covers adults and pediatric patients aged 16 years and older. Use of Adakveo in patients younger than 16 is not supported by established safety and efficacy data and therefore is outside the FDA‑indicated population and the policy's covered population.

Coding and Diagnosis Codes

Applicable HCPCSHCPCSCovered

J0791

Injection, crizanlizumab-tmca, 5 mg

Applicable ICD-10 CodesICD-10

D57.0	Hb-SS disease with crisis
D57.00	Hb-SS disease with crisis, unspecified
D57.01	Hb-SS disease with acute chest syndrome
D57.02	Hb-SS disease with splenic sequestration
D57.03	Hb-SS disease with cerebral vascular involvement
D57.04	Hb-SS disease with dactylitis
D57.09	Hb-SS disease with crisis with other specified complication
D57.1	Sickle-cell disease without crisis
D57.2	Sickle-cell/Hb-C disease
D57.20	Sickle-cell/Hb-C disease without crisis

1–10 of 52

1/6

VOCs in prior 12 months — initial eligibility

Threshold for initial eligibilityPatient has previously experienced 2 or more sickle cell–related vaso‑occlusive crises (VOCs) within the prior 12 months (unless transitioning from voxelotor).

Exception (transitioning from voxelotor)Patient transitioning from Oxbryta (voxelotor) to Adakveo may meet initial eligibility without meeting the >=2 VOCs threshold.

Minimum age for considerationPatient is 16 years of age or older.

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for initiation and continuation of Adakveo (crizanlizumab). Initial and reauthorization requests will be reviewed against the clinical criteria. Initial and continuation authorizations are limited to no more than 12 months.

Initial authorization: ≤ 12 months
Reauthorization: ≤ 12 months; continuation criteria must be met

Documentation Required

Documentation and Prescriber Requirements

Coverage requires documentation that the patient is not receiving concomitant chronic prophylactic blood transfusion therapy or concomitant Oxbryta (voxelotor) therapy. Adakveo must be prescribed by, or in consultation with, a hematologist or other specialist with expertise in sickle cell disease. Initial and maintenance dosing must follow FDA-approved labeling.

Definitions and Drug Description

Vaso‑occlusive crisis (VOC) — definition

Core definitionA vaso‑occlusive crisis (VOC) is an acute episode of pain with no cause other than a vaso‑occlusive event that requires a medical facility visit and treatment with oral or parenteral opioids, or parenteral NSAIDs.

Included related eventsAcute chest syndrome, hepatic sequestration, splenic sequestration, and priapism are considered VOCs when they require a visit to a medical facility.

Visit/treatment requirementVOC must lead to a healthcare visit and receipt of treatment (oral/parenteral opioids or parenteral NSAIDs) to qualify as a counted event.

Adakveo (crizanlizumab‑tmca) — mechanism

Mechanism of actionCrizanlizumab‑tmca is a humanized IgG2 kappa monoclonal antibody that binds to P‑selectin, blocking interactions that contribute to vaso‑occlusion.

Background

Sickle cell disease (SCD) is an inherited hemoglobin disorder characterized by abnormal hemoglobin that causes red blood cells to sickle under stress, leading to chronic hemolysis, vaso‑occlusion, and episodic acute pain known as vaso‑occlusive crises (VOCs). These VOCs and related complications (for example, acute chest syndrome, splenic or hepatic sequestration, and priapism) contribute to significant morbidity and progressive end‑organ damage. Adakveo is a monoclonal antibody that targets P‑selectin to reduce cellular interactions that contribute to vaso‑occlusion and has been shown in clinical study to reduce VOC frequency in patients aged 16 years and older.

Policy Revision History

2025-06-01policy_revisionLatest

Revised coverage criteria to allow coverage when the provider attests the patient is not an appropriate candidate for hydroxyurea based on genotype; added language that the policy does not apply to Arizona and updated references; archived previous policy version CS2025D0085L.

Policy Summary

PayerUnitedHealthcare

PolicyAdakveo (crizanlizumab-tmca) — Medical Benefit Drug Policy

Policy CodePolicy CS2025D0085M

Change TypeCoverage criteria revised; attestation alternative added

Effective DateJune 1, 2025

Next Review DateN/A

SourceLink

On This Page

Authorization length: Reauthorization will be for no more than 12 months

No concomitant chronic, prophylactic blood transfusion therapy
No concomitant Oxbryta (voxelotor) therapy
Prescribed by or in consultation with a hematologist or SCD specialist
Dosing must align with FDA-approved labeling

Denial Risk

Triggers for Potential Denial

Use in pediatric patients under 16 years of age is not supported by the policy and may be denied. Other triggers for potential denial include lack of required documentation (see hydroxyurea documentation options), presence of excluded indications (e.g., myelofibrosis), concurrent prohibited therapies, or failure to meet initial/continuation clinical criteria.

Age < 16 years — not supported; may be denied
Diagnosis outside covered indications (e.g., myelofibrosis) — not covered
Concurrent prohibited therapies (chronic transfusion, voxelotor) — potential denial
Missing required documentation or specialist consultation — potential denial

Documentation Required

Hydroxyurea Requirement / Consideration

Hydroxyurea use, intolerance, contraindication, or attestation is required as part of the coverage criteria. Coverage is appropriate when ONE of the following is documented: the patient is currently receiving hydroxyurea; the patient has a history of treatment failure, intolerance, or contraindication to hydroxyurea; or the provider attests the patient is not an appropriate candidate for hydroxyurea based on genotype (for example, the patient does not have homozygous hemoglobin SS [HbSS] or sickle beta 0 thalassemia).

Current hydroxyurea therapy documented; OR
History of hydroxyurea treatment failure, intolerance, or contraindication documented; OR
Provider attestation that patient is not an appropriate candidate for hydroxyurea based on genotype (e.g., not HbSS or sickle beta 0 thalassemia)

Note

Hydroxyurea Alternative (Provider Attestation)

As an alternative to documented hydroxyurea use or failure, the revised criteria allow coverage when the provider attests that the patient is an inappropriate candidate for hydroxyurea due to genotype. Note state-specific exceptions may apply (see state applicability).

Provider attestation may be used when genotype makes hydroxyurea inappropriate (e.g., patient does not have HbSS or sickle beta 0 thalassemia)
Check state or contractual requirements — some states (for example, Arizona Medicaid) may follow different clinical policies

Documentation Required

Benefit Plan Applicability

This policy interprets UnitedHealthcare standard benefit plans; actual coverage is subject to federal, state, or contractual plan terms. In the event of a conflict, the federal/state/contractual requirements govern. Supporting documentation may be requested to demonstrate plan applicability and to adjudicate exceptions.

Verify federal, state, or contractual benefit requirements — these govern if different from this policy
Some states (e.g., Arizona) may have different Medicaid clinical policies — refer to the state's coverage rationale
Be prepared to provide supporting documentation on request

Pharmacologic effect

Binding to P‑selectin blocks interactions between activated endothelium/platelets and blood cells and can dissociate preformed P‑selectin/PSGL‑1 complexes.

Clinical trial contextEfficacy evaluated in SUSTAIN, a randomized trial in patients with 2–10 VOCs in the prior 12 months, supporting reduction in VOC rate.

Not an appropriate candidate for hydroxyurea — definition

Genotype‑based attestationProvider may attest the patient is not an appropriate candidate for hydroxyurea based on genotype (i.e., the patient does not have homozygous hemoglobin SS [HbSS] or sickle beta0 thalassemia).

Alternative scenariosThe provider attestation alternative complements other criteria such as documented hydroxyurea intolerance, contraindication, or treatment failure.

Guidance to consult expertProfessional guidance recommends consulting a sickle cell expert for non‑HbSS genotypes (e.g., HbSC or HbS beta+ thalassemia) when considering hydroxyurea.