ModifiedUnitedHealthcarePolicy IEXD0085.10

Adakveo (crizanlizumab-tmca) for vasoocclusive crisis reduction in sickle cell disease

Defines medical necessity criteria, coding, and clinical rationale for UnitedHealthcare coverage of Adakveo in members with sickle cell disease (adults ≥16) to reduce vasoocclusive crises; applies to UnitedHealthcare benefit plans governed by this policy.

Policy Summary

PayerUnitedHealthcare

PolicyAdakveo (crizanlizumab-tmca) for vasoocclusive crisis reduction in sickle cell disease

Policy CodePolicy IEXD0085.10

Change TypeRevised coverage criteria

Effective DateJun 1, 2025

Next Review Date

Key ActionObtain prior authorization and document patient age (≥16), SCD genotype, VOC history or transition from voxelotor, hydroxyurea status or genotype-based attestation, and that dosing follows FDA labeling.

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).

Updated References section to reflect the most current information.

16+minimum patient age

≥2VOCs required (12 mo)

12 moapproval duration

Not allowed

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Not allowedwith chronic transfusion

Coverage Criteria for Adakveo (crizanlizumab-tmca)

Initial Therapy

Covered when ALL of the following are met for Initial Therapy

Initial Therapy — patient eligibility: Patient is 16 years of age or olderage >=16

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Initial Therapy — diagnosis: Diagnosis of a sickle cell disease (including, but not limited to, HbSS, HbSC, sickle beta0 thalassemia, sickle beta+ thalassemia)

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Initial Therapy — VOC requirement or transition: Patient is transitioning from Oxbryta (voxelotor) to Adakveo OR patient has experienced 2 or more sickle cell-related vaso-occlusive crises within the previous 12 months>= 2 VOCs in prior 12 months (when used for VOC criterion)

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Initial Therapy — hydroxyurea status: Patient is currently receiving hydroxyurea OR has history of treatment failure, intolerance, or contraindication to hydroxyurea OR provider attests patient is not an appropriate candidate for hydroxyurea based on genotype (patient does not have HbSS or sickle beta0 thalassemia)

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Initial Therapy — concomitant therapy exclusions: Patient is not receiving concomitant chronic prophylactic blood transfusion therapy AND not receiving concomitant Oxbryta (voxelotor)

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Initial Therapy — prescribing and dosing: Adakveo is prescribed by, or in consultation with, a hematologist or specialist with expertise in SCD AND initial dosing is in accordance with FDA‑approved labeling

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Initial Therapy — authorization duration: Initial authorization will be for no more than 12 months<= 12 months

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Continuation Therapy

Covered when ALL of the following are met for Continuation Therapy

Continuation Therapy — diagnosis: Diagnosis of a sickle cell disease (including, but not limited to, HbSS, HbSC, sickle beta0 thalassemia, sickle beta+ thalassemia)

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Continuation Therapy — clinical benefit: Patient has experienced a reduction in sickle cell–related vaso-occlusive crises and/or a decrease in severity of VOCs from pretreatment baseline while on Adakveo

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Continuation Therapy — concomitant therapy exclusions: Patient is not receiving concomitant chronic prophylactic blood transfusion therapy AND not receiving concomitant Oxbryta (voxelotor)

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Continuation Therapy — prescribing and dosing:

Initial coverage criteria

Covered when ALL of the following are met:

Age and diagnosis: Patient is aged 16 years or older and has a diagnosis of sickle cell disease (SCD).age >=16

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Intended use: Use is to reduce frequency of vaso-occlusive crises (VOCs).

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Prior therapy or contraindication: Either: a) patient has tried and had inadequate response or intolerance to hydroxyurea, or b) provider attests that the patient is not an appropriate candidate for hydroxyurea based on genotype (patient does not have HbSS or sickle beta0 thalassemia).

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Concomitant chronic prophylactic blood transfusion therapy and concomitant Oxbryta (voxelotor) therapy are excluded while a patient is receiving Adakveo. Requests for Adakveo may be denied if the member is actively receiving chronic, prophylactic transfusions or is concurrently treated with voxelotor; documentation must confirm the absence of these therapies before authorization is approved.

Use of Adakveo is excluded for pediatric patients younger than 16 years. The FDA indicates that the safety and efficacy of Adakveo have not been established in patients below age 16, and the policy follows that age-based exclusion for coverage decisions.

Use of Adakveo is considered not medically necessary when the requirements for initial or continuation therapy are not met. Examples include lack of documented history of vaso-occlusive crises meeting policy thresholds, absence of demonstrated clinical benefit during continuation, receipt of disallowed concomitant therapies (chronic transfusion or Oxbryta), or dosing/prescribing inconsistent with FDA labeling and specialist involvement requirements.

Coding — Diagnosis and Procedure Codes

Applicable ICD-10 Diagnosis 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.

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Relevant HCPCS (example from drug coverage context)HCPCS

J3358

Injection, crizanlizumab-tmca, 1 mg (HCPCS code commonly used for crizanlizumab)

VOC frequency requirement

Minimum VOCs in prior 12 months>= 2 sickle cell–related VOCs in the previous 12 months

Alternate pathwayTransitioning from Oxbryta (voxelotor) to Adakveo satisfies VOC requirement

Source contextRequirement applied to initial therapy eligibility in policy Initial Therapy criteria

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for Adakveo (crizanlizumab-tmca). Initial and reauthorization approvals are limited to no more than 12 months.

Prior authorization required
Initial and reauthorization duration: ≤ 12 months

Denial Risk

Age-Based Requirement and Denial Risk

Adakveo is indicated for patients aged 16 years and older. Requests for patients younger than 16 may be denied because safety and efficacy have not been established in pediatric patients below age 16.

Age requirement: ≥ 16 years
Denial risk for patients < 16 years

Definitions

Vasoocclusive crisis (VOC) — Definition and clinical criteria

DefinitionAn acute episode of pain due to vasoocclusion requiring a visit to a medical facility and treatment with oral or parenteral opioids or parenteral NSAIDs; includes acute chest syndrome, hepatic sequestration, splenic sequestration, and priapism when requiring a facility visit.

Clinical featuresCaused by sickled red blood cells obstructing blood flow leading to acute pain, vasoocclusion, inflammation, and end-organ effects

Trial inclusion criteriaSUSTAIN enrolled patients with 2–10 VOCs in the prior 12 months; primary outcome measured annual rate of VOCs leading to a healthcare visit

Adakveo (crizanlizumab-tmca)

Drug definition and mechanismAdakveo (crizanlizumab-tmca) is a humanized IgG2 kappa monoclonal antibody that binds P-selectin, blocking interactions with ligands including PSGL-1 and dissociating preformed P‑selectin/PSGL‑1 complexes to inhibit cell interactions that contribute to vasoocclusion.

Background

Sickle cell disease (SCD) is an inherited hemoglobin disorder characterized by hemolysis, vaso-occlusion, anemia, inflammation, and episodic painful crises known as vaso-occlusive crises (VOCs). Adakveo (crizanlizumab-tmca) is a humanized monoclonal antibody that targets P-selectin to inhibit cellular interactions that contribute to vaso-occlusion. Adakveo is indicated to reduce the frequency of VOCs in patients with SCD aged 16 years and older; clinical trials such as SUSTAIN evaluated its efficacy in decreasing VOC frequency and delaying time to first and subsequent crises.

Policy Revision History

2025-06-01material_revisionLatest

Revised coverage criteria to add that coverage is allowed when the provider attests the patient is not an appropriate candidate for hydroxyurea based on genotype (patient does not have HbSS or sickle beta0 thalassemia); references section updated and prior version IEXD0085.09 archived.

Policy Summary

PayerUnitedHealthcare

PolicyAdakveo (crizanlizumab-tmca) for vasoocclusive crisis reduction in sickle cell disease

Policy CodePolicy IEXD0085.10

Change TypeRevised coverage criteria

Effective DateJun 1, 2025

Next Review Date

SourceLink

On This Page

Adakveo is prescribed by, or in consultation with, a hematologist or specialist with expertise in SCD AND maintenance dosing is in accordance with FDA‑approved labeling

Continuation Therapy — authorization duration: Reauthorization will be for no more than 12 months<= 12 months

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Documentation Required

Required Documentation

Provider must document patient age, diagnosis (including genotype when relevant), history of vasoocclusive crises (VOCs), and prior therapy attempts or a provider attestation when appropriate.

Document age and diagnosis/genotype
Document VOC history (e.g., number in prior 12 months)
Document prior hydroxyurea therapy attempts, intolerance, or contraindication, or provide attestation

Prior Authorization

Hydroxyurea Requirement / Consideration

Hydroxyurea should be used or considered prior to Adakveo per NHLBI recommendations. Providers should document current hydroxyurea use, a history of treatment failure, intolerance, or contraindication to hydroxyurea, or provide a provider attestation that hydroxyurea is not appropriate for the patient.

Patient currently receiving hydroxyurea: document therapy
History of hydroxyurea failure/intolerance/contraindication: document

Documentation Required

Genotype-Based Hydroxyurea Ineligibility Attestation

Policy allows coverage of Adakveo when the provider attests that the patient is not an appropriate candidate for hydroxyurea based on genotype (for example, the patient does not have HbSS or sickle beta0 thalassemia), consistent with the revised coverage criteria.

Provider attestation acceptable when genotype makes hydroxyurea inappropriate (e.g., HbSC or HbS beta+ thalassemia)
If used, provider attestation must be documented in the medical record

Indication summaryIndicated to reduce the frequency of vasoocclusive crises (VOCs) in patients with sickle cell disease aged 16 years and older.

Pediatric noteSafety and efficacy have not been established in pediatric patients below age 16.

Vaso-occlusive crisis (VOC) — alternate/related definition and Adakveo relation

Alternate/related VOC descriptionVOCs include acute chest syndrome, hepatic sequestration, splenic sequestration, and priapism when they require a medical facility visit and opioid or parenteral NSAID treatment.

Relation to Adakveo indicationAdakveo was evaluated in patients with histories of 2–10 VOCs and is indicated to reduce VOC frequency in patients aged ≥16.

Clinical trial contextSUSTAIN defined VOCs as acute pain events requiring a healthcare visit and opioid or parenteral NSAID treatment; trial eligibility required 2–10 VOCs in prior 12 months.