ModifiedCentenePolicy CP.PHAR.451

Clinical Policy: Voxelotor (Oxbryta)

This policy governs medical necessity and coverage criteria for voxelotor (Oxbryta) for members with sickle cell disease across Centene lines of business, including guidance for continuation therapy following the manufacturer's market withdrawal.

Policy Summary

PayerCentene

PolicyClinical Policy: Voxelotor (Oxbryta)

Policy CodePolicy CP.PHAR.451

Change TypeMaterial revisions — manufacturer withdrawal and continued therapy updates

Effective DateN/A

Next Review DateN/A

Key ActionDo not initiate Oxbryta; submit prior authorization only for continuation with documentation of prior use, Hb increase ≥1 g/dL, and provider attestation of market withdrawal awareness.

SourceLink

POLICY UPDATE CHANGES

Initial approval criteria were removed due to manufacturer withdrawal; continued therapy requirements were updated to require attestation of market withdrawal awareness and collaboration on next treatment steps and approval duration revised.

Appendix E documents Pfizer's voluntary withdrawal of Oxbryta from worldwide markets and advises that patients should no longer be prescribed Oxbryta.

Dosage adjustments for strong and moderate CYP3A4 inducers are specified with higher maximum daily doses.

NoInitial therapy initiation allowed

>=1 g/dLHb increase required

1,500 mgStandard adult dose

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Max dose with strong inducer

Age ≥4 yearsFDA-approved population

1 monthContinued therapy duration

Coverage Criteria for Voxelotor (Oxbryta)

Continued Therapy (Sickle Cell Disease)

Covered when ALL of the following are met:

Continued therapy eligibility: Member meets one of: (a) currently receiving medication via Centene benefit or previously met initial approval criteria; OR (b) currently receiving medication and enrolled in a state/product with continuity of care regulations.

See continuity of care addendums (CC.PHARM.03A and CC.PHARM.03B).

Response to therapy: Member is responding positively to therapy as evidenced by an increase in hemoglobin (Hb) from baseline of at least 1 g/dL.>=1 g/dL

Provider attestation: Provider must attest they acknowledge the market withdrawal of Oxbryta and are actively collaborating with the member to establish next steps in the treatment plan.

See Appendix E for market withdrawal information.

Concomitant therapy restrictions: Oxbryta should be prescribed concurrently with hydroxyurea unless contraindicated or clinically significant adverse effects occur; Oxbryta must not be prescribed concurrently with Adakveo.

Adakveo redirection was removed per updated trial results (see Appendix D).

Dose limit checks: If request is for a dose increase, the new dose must not exceed: (a) 2,500 mg/day if concurrently taking a strong CYP3A4 inducer; (b) 2,000 mg/day if taking a moderate CYP3A4 inducer; (c) 1,500 mg/day for all others.<= dose limits per inducer status

Age/weight-based dosing and inducer examples are in Appendix V and Appendix D respectively.

Continued Therapy after Market Withdrawal

Policy-level changes and criteria context

Manufacturer withdrawal impacts: Initial approval criteria were removed due to the manufacturer's voluntary withdrawal of Oxbryta; continued therapy approval duration was revised to 1 month and continued therapy requires provider attestation of market withdrawal awareness and active collaboration on next treatment steps.

See Appendix E for Pfizer's market withdrawal announcement and guidance that patients should no longer be prescribed Oxbryta.

Non–FDA approved indications for voxelotor (Oxbryta) that are not specifically addressed in this policy are not authorized unless the provider supplies sufficient clinical documentation demonstrating efficacy and safety per the plan off‑label use policies (for example, CP.CPA.09 for commercial, HIM.PA.154 for marketplace, or CP.PMN.53 for Medicaid) or an applicable evidence of coverage document.

Following Pfizer’s voluntary worldwide withdrawal of Oxbryta for the treatment of sickle cell disease, Pfizer has advised that patients should no longer be prescribed Oxbryta and should contact their physicians to discuss alternative treatments. The manufacturer’s announcement underlies the policy change that initiation of therapy is no longer permitted; providers should follow Appendix E for details on the withdrawal and clinical rationale.

As a result of the manufacturer’s market withdrawal, the policy has been updated to remove the prior initial approval criteria for Oxbryta. This operational change means initial approvals have been eliminated and any requests to start therapy should be evaluated per the revised policy context and withdrawal guidance (see Appendix E).

Initiation of Oxbryta is expressly not permitted under this policy. Per the Initial Approval section, members may not initiate therapy with Oxbryta; authorization for new starts will be denied. Continuation of therapy for members already receiving Oxbryta is addressed separately and requires meeting the continued therapy criteria.

Coding and Diagnosis Support

ICD-10 codes that support coverageICD-10

D57.0*	Hb-SS disease with crisis
D57.1	Sickle-cell disease without crisis
D57.2*	Sickle-cell/Hb-C disease
D57.4*	Sickle-cell thalassemia

ICD-10 supporting diagnosesICD-10Covered

D57.0*	Hb-SS disease with crisis
D57.1	Sickle-cell disease without crisis
D57.2*	Sickle-cell/Hb-C disease
D57.4*	Sickle-cell thalassemia

inv-09: Hemoglobin increase from baseline — threshold value for continued therapy

Hemoglobin increase from baseline>= 1 g/dL

Criteria contextRequired as evidence of positive response to continued therapy

Where recordedDifference between baseline Hb and most recent Hb while on therapy

Provider Requirements and Prior Authorization

Prior Authorization

Initiation Not Permitted

Authorization is not permitted. Member may not initiate therapy with Oxbryta. If member is currently using Oxbryta, continuation requests must follow the continued therapy criteria. Approval duration for initiation: Not applicable.

Affected product: Oxbryta
Initiation requests: Deny — initiation not permitted per policy

Documentation Required

Required Documentation

Provider must submit documentation (such as office chart notes, lab results, or other clinical information) supporting that the member has met all approval criteria for continued therapy.

Acceptable documentation includes office notes, laboratory values (including baseline and on-therapy hemoglobin), and other clinical records.

Background

Voxelotor is a small‑molecule hemoglobin S (HbS) polymerization inhibitor that received accelerated approval for treatment of sickle cell disease based on increases in hemoglobin. The manufacturer announced a voluntary global withdrawal of Oxbryta after review of clinical data indicating concerns about the balance of benefit and risk, including potential imbalances in vaso‑occlusive crises and fatal events; Pfizer advises that patients should no longer be prescribed Oxbryta and should consult their clinicians regarding alternative treatments and discontinuation considerations.

Definitions and Key Terms

inv-19: Voxelotor / Oxbryta — drug name key value

Drug name (generic)Voxelotor

Brand nameOxbryta

Mechanism/descriptionHemoglobin S (HbS) polymerization inhibitor

inv-20: CYP3A4 inducer — examples and dosing impact for co-administration

Strong CYP3A4 inducers — examplesapalutamide, carbamazepine, phenobarbital, phenytoin, rifampin

Moderate CYP3A4 inducers — examplesbosentan, dabrafenib, efavirenz, mitapivat, modafinil, rifabutin, rifapentine

Dosing impact — strong inducer

Policy Summary

PayerCentene

PolicyClinical Policy: Voxelotor (Oxbryta)

Policy CodePolicy CP.PHAR.451

Change TypeMaterial revisions — manufacturer withdrawal and continued therapy updates

Effective DateN/A

Next Review DateN/A

Key ActionDo not initiate Oxbryta; submit prior authorization only for continuation with documentation of prior use, Hb increase ≥1 g/dL, and provider attestation of market withdrawal awareness.

SourceLink

On This Page

Prior Authorization

Continuation Therapy Prior Authorization

Continued therapy prior authorization is required and will be granted only when all continued therapy criteria are met. Note: initial therapy prior authorization is not permitted (see Initiation Not Permitted).

Continued therapy approvals revised to 1 month duration following manufacturer market withdrawal.
Provider must attest they are aware of the Oxbryta market withdrawal and are actively collaborating with the member on next treatment steps.

Documentation Required

Prior Authorization — Continued Therapy Attestation

Providers must attest to awareness of the Oxbryta market withdrawal and document active collaboration with the member to establish next steps in the treatment plan.

This attestation is required for continued therapy approvals.
Market withdrawal information and guidance are available in Appendix E.

Note

Therapeutic Alternatives

Therapeutic alternatives to consider include hydroxyurea and L-glutamine (Endari). These agents are listed in Appendix B. Note that listed alternatives may require their own prior authorization depending on line of business.

Hydroxyurea (Droxia, Siklos) dosing and limits provided in Appendix B.
L-glutamine (Endari) dosing and limits provided in Appendix B.

Documentation Required

Supporting Diagnosis Codes

Provider must ensure documentation supports one of the listed ICD-10-CM diagnoses for sickle cell disease when requesting continued therapy.

Supported diagnosis codes include: D57.0*, D57.1, D57.2*, D57.4*.

Denial Risk

Market Withdrawal Impacts Authorization

Market withdrawal of Oxbryta by the manufacturer affects authorization processes: initial approval criteria were removed and continued therapy approvals were revised to a 1-month duration. Providers should note these changes and collaborate with patients on treatment transitions.

Pfizer voluntarily withdrew Oxbryta for SCD on September 25, 2024; prescribing new patients is not advised.
Continued therapy approvals now require monthly reauthorization and provider attestation regarding withdrawal awareness.

Maximum 2,500 mg PO QD for patients taking a strong CYP3A4 inducer

Dosing impact — moderate inducerMaximum 2,000 mg PO QD for patients taking a moderate CYP3A4 inducer

inv-21: ICD-10-CM diagnoses supporting coverage — list of relevant D57.* codes

D57.0*Hb-SS disease with crisis

D57.1Sickle-cell disease without crisis

D57.2*Sickle-cell/Hb-C disease

D57.4*Sickle-cell thalassemia