CurrentUnitedHealthcarePolicy CS2O25D00120K

Gene Therapies for Hemophilia B

UnitedHealthcare Medical Benefit Drug Policy governing medical necessity criteria, exclusions, monitoring, provider requirements, and applicable codes for single-dose gene therapies Beqvez (fidanacogene elaparvovec-dzkt) and Hemgenix (etranacogene dezaparvovec-drlb) for treatment of hemophilia B in adults. Includes state-specific applicability exceptions.

Policy Summary

PayerUnitedHealthcare

PolicyGene Therapies for Hemophilia B

Policy CodePolicy CS2O25D00120K

Change TypeState-specific application exception added

Effective DateMay 1, 2025

Next Review Date

Key ActionAuthorization will be issued for no more than one treatment per lifetime and for no longer than 45 days from approval.

POLICY UPDATE CHANGES

Application Virginia: Added language to indicate this Medical Benefit Drug Policy does not apply to Hemgenix for the state of Virginia; refer to the state's Medicaid clinical policy.

2Gene therapies addressed

1Lifetime treatments authorized per patient

18+Minimum age (years)

Coverage Summary

This policy governs single-dose gene therapies Beqvez (fidanacogene elaparvovec-dzkt) and Hemgenix (etranacogene dezaparvovec-drlb) for treatment of hemophilia B in adults, specifying medical necessity criteria, exclusions, monitoring, provider requirements, and applicable codes. Coverage stance is mixed. The policy authorizes a maximum of one lifetime treatment per patient and requires recipients to be at least 18 years of age. Note: this Medical Benefit Drug Policy does not apply to Hemgenix for the state of Virginia; refer to the state's Medicaid clinical policy for Hemgenix in Virginia.

Initial Therapy Criteria — Hemgenix

Hemgenix - Medical Necessity Criteria

Hemgenix is proven and medically necessary when ALL of the following are met:

ALL of the following

Diagnosis requirement
- Patient is 18 years of age or older
- Severe hemophilia B branch
  - Severe factor IX threshold: Diagnosis of severe hemophilia B< 0.01 IU/mL
    Documentation of endogenous factor IX levels less than 1% of normal Factor IX
- Moderately severe hemophilia B branch
  - Moderately severe factor IX threshold: Documentation of endogenous factor IX levels ≥ 1% and < 2% (≥ 0.01 IU/mL to ≤ 0.02 IU/mL)>= 0.01 IU/mL to <= 0.02 IU/mL
  - Diagnosis of moderately severe hemophilia B
  - Bleeding history
    Patient has current or historical life-threatening hemorrhage
    Patient has repeated, serious spontaneous bleeding episodes
Prior therapy / exposure requirement
- Chronic prophylaxis branch
  - Patient is currently receiving chronic prophylactic Hympavzi (marstacimab-hncq) therapy
- Factor IX prophylaxis and exposure branch
  - Patient currently uses factor IX prophylaxis therapy
  - >= 50 exposure days
    Patient has had a minimum of 50 exposure days to a factor IX agent
Additional clinical and testing requirements
- Candidate determination: Patient has been determined to be an appropriate candidate for Hemgenix by the Hemophilia Treatment Center based on willingness to adhere to initial and long-term monitoring and management
- Inhibitor history: Patient does not have a history of inhibitors to factor IX ≥ 0.6 Bethesda units (BU)>= 0.6 BU
- Immune tolerance induction: Patient has not gone through immune tolerance induction (ITI)
- Active inhibitor screen: Patient does not screen positive for active factor IX inhibitors (≥ 0.6 BU) prior to administration of Hemgenix>= 0.6 BU

Continuation Therapy & Monitoring Requirements

Documentation Required

Post-treatment monitoring attestation

Prescribers must attest that liver enzymes (ALT and AST) and factor IX activity will be monitored at least weekly after gene therapy administration: for Beqvez, at least weekly for a minimum of 4 months; for Hemgenix, at least weekly for a minimum of 3 months. Monitoring should continue thereafter according to the schedule in the product prescribing information.

ALT and AST — at least weekly (Beqvez: ≥4 months; Hemgenix: ≥3 months)
Factor IX activity — at least weekly (Beqvez: ≥4 months; Hemgenix: ≥3 months)

Documentation Required

Follow-up data may be requested

UnitedHealthcare may request follow-up data from the prescriber for quality-assurance purposes. Requests will not be more frequent than twice per year and may occur for up to 5 years following treatment. This information is for quality only and will not be used as part of the individual coverage decision.

Potential requests may include evaluation of factor IX expression, breakthrough bleeding episodes, factor IX product utilization, and inhibitor development
Requests not more frequent than biannually and not to exceed 5 years post-treatment
Data requested are for quality purposes only and are not part of the individual coverage decision

Documentation Required

Pre-treatment testing requirements

Before treatment, prescribers must perform and document appropriate baseline testing to support safe administration and eligibility, including liver health assessment and testing for factor IX inhibitors and relevant viral/hepatitis status.

Liver enzyme testing: ALT, AST, alkaline phosphatase (ALP), and total bilirubin
Hepatic imaging as appropriate: hepatic ultrasound and/or elastography to rule out radiologic liver abnormalities
Testing for hepatitis B surface antigen and hepatitis C antibody (with HCV RNA if antibody positive)
HIV testing and viral load as applicable (patients with HIV must be virally suppressed, <200 copies/mL)
Assessment for preexisting neutralizing antibodies to the relevant AAV vector (per product requirements)
Baseline factor IX activity and inhibitor testing (Bethesda assay); documentation that inhibitors < 0.6 BU prior to administration

Prior Authorization, Documentation & Prescriber Requirements

Prior Authorization

Prior authorization requirement and limits

Prior authorization is required. Authorization will be issued for no more than one treatment per lifetime and is valid for up to 45 days from approval.

Affected codes: J1411, J1414
No more than one treatment per lifetime
Authorization valid up to 45 days from approval

Documentation Required

HTC prescriber and candidate determination requirement

Beqvez and Hemgenix must be prescribed and managed by a bleeding disorder specialist on staff at a Hemophilia Treatment Center (HTC) that holds Federal designation as listed in the CDC HTC directory. The HTC must determine the patient is an appropriate candidate and the prescriber must document that determination and the patient's willingness to adhere to initial and long-term monitoring and management.

Documentation Required

Required pre-treatment testing

Required pre-treatment testing includes measurement of endogenous factor IX levels, Bethesda inhibitor testing, evaluation for neutralizing anti-AAV antibodies using specified or CLIA-validated tests appropriate to the product (AAVRh74var for Beqvez; AAV5 for Hemgenix), and liver health assessments including ALT, AST, ALP, total bilirubin and hepatic imaging (ultrasound and/or elastography).

Endogenous factor IX level
Bethesda inhibitor testing (inhibitor level in BU)
Anti-AAV neutralizing antibody testing per product (AAVRh74var for Beqvez; AAV5 for Hemgenix) using specified/CLIA-validated tests
Liver assessments: ALT, AST, ALP, total bilirubin
Hepatic imaging: ultrasound and/or elastography

Documentation Required

Counseling attestation (alcohol risks)

Prescriber must attest that counseling regarding the risks of alcohol consumption following administration of the gene therapy has been provided to the patient.

Not Medically Necessary / Exclusions

Beqvez and Hemgenix are unproven and not medically necessary in the following situations:

ALL of the following

Exclusions
- Repeat administration of Hemgenix or Beqvez for the treatment of hemophilia B
- Hemophilia A exclusion: Treatment of hemophilia A
- Prior gene therapy recipients: Treatment of hemophilia B after previously receiving another factor IX gene therapy product
- Age exclusion: Treatment of hemophilia B in patients less than 18 years of age< 18 years
- Routine combination therapy exclusion: Routine combination treatment with chronically administered prophylactic therapy for hemophilia B

Clinical Evidence

45Beqvez study population: 45 adult male patients; mean ABR post-treatment 2.5 vs baseline 4.5 bleeds/yr

2.5Beqvez mean post-treatment ABR (bleeds/yr)

54Hemgenix study population: 54 adult male patients; mean ABR months 7–18 = 1.9 vs lead-in 4.1; ABR ratio 0.46

0.46Hemgenix ABR ratio (months 7–18 vs lead-in)

Clinical trials demonstrated that both therapies reduced annualized bleeding rates (ABR) compared with lead-in/baseline prophylaxis: Beqvez (45 adult males) had a mean baseline ABR of 4.5 bleeds/year versus post-treatment ABR of 2.5 bleeds/year, meeting the noninferiority criterion; Hemgenix (54 adult males) showed an estimated mean ABR of 1.9 bleeds/year during months 7–18 versus a lead-in ABR of 4.1 bleeds/year (ABR ratio 0.46). Common adverse events and FDA labeling warnings for these products include elevated liver enzymes/hepatotoxicity (e.g., ALT/AST elevations), infusion-related reactions, flu-like symptoms, headache, creatine kinase elevations, fatigue/malaise, and immune-mediated issues related to anti-AAV antibodies; Hemgenix labeling also notes potential hepatocellular carcinogenicity and the need for laboratory monitoring.

Background & Definitions

Beqvez and Hemgenix are each approved as a single-dose intravenous (IV) AAV-based gene therapy given once to adults with moderately severe to severe hemophilia B. Beqvez uses an AAVRh74var capsid delivering a high-activity factor IX transgene (FIX-R338L/Padua) to transduce hepatocytes and increase circulating factor IX activity. Hemgenix uses an AAV5 vector carrying a codon-optimized Padua variant of human FIX expressed in the liver to raise blood factor IX levels and reduce bleeding.

Term	Definition
HTC
Bethesda units (BU)

Policy Summary

PayerUnitedHealthcare

PolicyGene Therapies for Hemophilia B

Policy CodePolicy CS2O25D00120K

Change TypeState-specific application exception added

Effective DateMay 1, 2025

Next Review Date

Key ActionAuthorization will be issued for no more than one treatment per lifetime and for no longer than 45 days from approval.

On This Page

OpenPayer

Gene Therapies for Hemophilia B

Coverage Summary

Initial Therapy Criteria — Beqvez

Initial Therapy Criteria — Hemgenix

Continuation Therapy & Monitoring Requirements

Prior Authorization, Documentation & Prescriber Requirements

Not Medically Necessary / Exclusions

Applicable Codes

Clinical Evidence

Background & Definitions

Revision History

J1411	Injection, etranacogene dezaparvovec-drlb, per therapeutic dose
J1414	Injection, fidanacogene elaparvovec-dzkt; per therapeutic dose