CurrentMass General Brigham Health PlanPolicy 067

Hemgenix (etranacogene dezaparvovec-drlb) gene therapy for Hemophilia B

Defines prior authorization, medical necessity criteria, dosing, facility and patient eligibility requirements for Hemgenix gene therapy for members of Mass General Brigham Health Plan and variations for Medicare, MassHealth, One Care and SCO plans.

Policy Summary

PayerMass General Brigham Health Plan

PolicyHemgenix (etranacogene dezaparvovec-drlb) gene therapy for Hemophilia B

Policy CodePolicy 067

Change TypeThreshold and administrative updates

Effective Date

Next Review Date

Key ActionObtain prior authorization and document baseline ABR, FIX activity, FIX inhibitor, AAV5 neutralizing antibody, renal and liver tests, and serologies before treatment.

SourceLink

POLICY UPDATE CHANGES

Added variation for One Care and SCO members and updated prior authorization table.

Neutralizing antibody to AAV5 threshold changed to 1:700.

Summary of evidence section added.

≥18minimum age for treatment

≤2% FIXbaseline FIX activity

>150prior exposure days

1:700max AAV5 nAb titer

Policy Summary

PayerMass General Brigham Health Plan

PolicyHemgenix (etranacogene dezaparvovec-drlb) gene therapy for Hemophilia B

Policy CodePolicy 067

Change TypeThreshold and administrative updates

Effective Date

Next Review Date

Key ActionObtain prior authorization and document baseline ABR, FIX activity, FIX inhibitor, AAV5 neutralizing antibody, renal and liver tests, and serologies before treatment.

SourceLink

On This Page

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Coverage & Medical Necessity Criteria

Initial Approval

Covered when ALL of the following are met:

Initial Approval: Authorization of a single treatment may be granted to biologic male (or male assigned at birth) members 18 years of age or older for treatment of moderately severe or severe Hemophilia B (congenital Factor IX deficiency documented FIX activity level ≤ 2% of normal) when ALL of the following are met:

Diagnostic confirmation: Documentation of Hemophilia B established by either current use of FIX prophylaxis therapy OR baseline Annualized Bleeding Rate (ABR) showing current or historical life‑threatening hemorrhage or repeated, serious spontaneous bleeding episodes.

Baseline ABR will be documented for outcomes monitoring and shall have no bearing on the decision to approve or deny.

Age and severity: Member is ≥ 18 years of age and has moderately severe or severe Hemophilia B (baseline FIX activity ≤ 2% of normal).≤ 2% of normal

Prior prophylaxis: Member has received continuous FIX protein prophylaxis for > 2 months.

Prior exposure: Member has had > 150 previous exposure days of treatment with FIX protein within their lifetime.> 150 lifetime exposure days

No concurrent immunosuppression or malignancy: Member is not currently receiving immunosuppressive therapy and does not have any current malignancies.

No prior gene therapy: Member has not received Hemgenix or any other gene therapy.

Additional courses of therapy are considered experimental and investigational.

Required pre-treatment testing: Documentation required for: baseline ABR; FIX activity level; FIX inhibitor level (< 0.6 Bethesda units); neutralizing antibody to AAV5 (< 1:700); creatinine and estimated creatinine clearance; AST, ALT, bilirubin, ALP; serologies for HIV, hepatitis B and C; and weight.FIX inhibitor < 0.6 BU; AAV5 neutralizing antibody < 1:700; estimated creatinine clearance ≥ 30 mL/min

Individuals with history of transient FIX inhibitor must document ≥ 6 months since positive test with ≥ 2 negative FIX inhibitor tests during that period.

Renal and hepatic function: Estimated creatinine clearance ≥ 30 mL/min and creatinine up to 2× ULN; liver function tests (ALT, AST, bilirubin, ALP) ≤ 2× ULN and no evidence of stage 3–4 cirrhosis unless a consulting hepatologist has assessed the member as eligible.Estimated creatinine clearance ≥ 30 mL/min; LFTs ≤ 2× ULN

Infection and immunologic status: No active infection, no chronic or active hepatitis B or C (or evidence of HCV eradication after treatment), and no immunosuppressive disorder including uncontrolled HIV.

Dosing and Duration

Dosing: Single intravenous dose containing a minimum of 2.0 x 10^13 genome copies per kg (body weight based on weight prior to first apheresis). Dosing should follow the package insert.minimum 2.0 x 10^13 gc/kg

Timing: Single treatment course must be administered within three months of approval.

Additional courses of therapy are considered experimental/investigational.

Facility and Prescriber

Prescriber: Medication must be prescribed by a hematologist.

Facility: Treatment must be administered at a Comprehensive Hemophilia Treatment Center.

Additional courses of Hemgenix therapy beyond the single authorized treatment course are considered experimental and investigational and are not covered.

Use of Hemgenix in patients who do not meet the listed eligibility criteria is considered not medically necessary and will be denied. This includes patients with inadequate renal or hepatic function (see estimated creatinine clearance and LFT thresholds), presence of AAV5 neutralizing antibodies at or above 1:700, active infection or unresolved hepatitis, active malignancy, ongoing immunosuppression (including HIV), or prior gene therapy.

Coding and Key Clinical Thresholds

Informational HCPCSHCPCS

J1411

Injection, etranacogene dezaparvovec-drlb, per therapeutic dose

inv-07: Neutralizing antibody to AAV5 — threshold value

ThresholdNeutralizing antibody to AAV5 titer must be less than 1:700 for eligibility

Policy changeThreshold revised to 1:700 in recent ad hoc update

Documentation requirementNeutralizing antibody to AAV5 must be documented prior to treatment

inv-08: Baseline FIX activity — ≤ 2% of normal

ThresholdBaseline FIX activity ≤ 2% of normal

Severity definitionQualifies as moderately severe or severe Hemophilia B

Documentation

Prior Authorization, Documentation & Denial Triggers

Prior Authorization

Prior Authorization Required

Prior authorization is required for Hemgenix for Commercial, ACO, Medicare Advantage, One Care and SCO members. Prior authorization for Commercial and Qualified Health Plan members is managed by Prime Therapeutics; prior authorization for Mass General Brigham ACO members is managed by the MassHealth Drug Utilization Review Program.

Prime Therapeutics manages prior authorization for Commercial and Qualified Health Plan members.
MassHealth Drug Utilization Review Program manages prior authorization for Mass General Brigham ACO members.

Documentation Required

Prior Prophylaxis Requirement

Members must have received continuous FIX protein prophylaxis for greater than 2 months prior to approval.

Background and Evidence Summary

Hemgenix is an adeno-associated virus serotype 5 (AAV5)–based gene therapy that delivers a Padua-enhanced factor IX (FIX) transgene for patients with congenital Hemophilia B. Clinical trial evidence demonstrates substantial increases in FIX activity and reductions in annualized bleeding rates after a single intravenous administration; safety considerations include infusion-related reactions, hepatotoxicity and the need for close laboratory monitoring prior to and after treatment. Authorization is limited to a single treatment course administered as a single intravenous dose containing a minimum of 2.0 x 10^13 genome copies per kg, and repeat courses are considered experimental/investigational.

Definitions and Abbreviations

inv-18: ABR — Baseline Annualized Bleeding Rate (ABR)

DefinitionBaseline Annualized Bleeding Rate (ABR)

UseBaseline ABR is documented for outcomes monitoring and does not determine approval decisions

DocumentationABR must be included in required pre-treatment testing (historical or current)

inv-19: AAV5 neutralizing antibody — Neutralizing antibody titer to AAV5; policy threshold for eligibility is less than 1:700.

ThresholdNeutralizing antibody titer to AAV5 must be less than 1:700 for eligibility

Denial triggerPresence of AAV5 neutralizing antibody ≥1:700 will result in denial or not medically necessary determination

FIX activity level must be documented as part of pre-treatment testing

inv-09: Prior exposure days to FIX protein — > 150 lifetime exposure days

Threshold> 150 lifetime exposure days to FIX protein

Requirement contextMember must have >150 previous exposure days within their lifetime

DocumentationPrior exposure history must be provided as part of initial authorization

inv-10: Estimated creatinine clearance — ≥ 30 mL/min

ThresholdEstimated creatinine clearance ≥ 30 mL/min

Additional renal criterionCreatinine levels may be up to 2x ULN

DocumentationCreatinine and estimated creatinine clearance must be documented prior to treatment

inv-11: Liver function tests — ALT/AST/bilirubin/ALP ≤ 2x ULN (unless hepatologist clearance)

ThresholdALT, AST, bilirubin, and alkaline phosphatase (ALP) ≤ 2x upper limit of normal

ExceptionIndividuals with stage 3–4 cirrhosis may be eligible only with consulting hepatologist clearance

DocumentationLiver function tests must be documented as part of pre-treatment testing

inv-12: FIX inhibitor at screening — < 0.6 Bethesda units

ThresholdFIX inhibitor at screening must be less than 0.6 Bethesda units

Transient inhibitor historyIf prior transient FIX inhibitor, require ≥6 months since positive test with ≥2 negative tests during that period

DocumentationFIX inhibitor level must be included in required pre-treatment testing

Documentation Required

Required Clinical & Laboratory Documentation

Documentation required for initial approval includes baseline and screening clinical and laboratory results to demonstrate eligibility and to support outcomes monitoring.

Baseline Annualized Bleeding Rate (ABR) — documented for outcomes monitoring
FIX activity level
FIX inhibitor level (must be < 0.6 Bethesda units)
Neutralizing antibody to AAV5 (must be < 1:700)
Creatinine and estimated creatinine clearance (creatinine clearance ≥ 30 mL/min; creatinine up to 2× ULN allowed)
Liver function tests: AST, ALT, bilirubin, alkaline phosphatase (ALP) (no greater than 2× ULN unless hepatologist documents eligibility; no evidence of stage 3–4 cirrhosis unless approved by hepatologist)
Serologic testing for HIV, hepatitis B, and hepatitis C (evidence of hepatitis C eradication if recently treated)
Weight

Denial Risk

Triggers for Denial

Requests will be denied if the member does not meet all initial approval criteria. Common triggers for denial include not meeting age, disease severity, exposure, inhibitor, antibody, renal, or hepatic requirements.

Age less than 18 years (authorization limited to biologic males or male-assigned-at-birth age ≥ 18)
Baseline FIX activity > 2% of normal (does not meet moderately severe/severe Hemophilia B threshold)
Insufficient history of continuous FIX prophylaxis (> 2 months required)
Fewer than 150 prior exposure days to FIX protein
Current receipt of immunosuppressive therapy
Any current malignancy
Prior receipt of Hemgenix or any other gene therapy
Missing required documentation (ABR, FIX activity, FIX inhibitor level, neutralizing antibody to AAV5, creatinine, LFTs, HIV/hepatitis serology, weight)
FIX inhibitor ≥ 0.6 Bethesda units (or insufficient documentation of resolution — transient inhibitor requires ≥ 6 months since positive test with ≥ 2 negative tests)
Neutralizing antibody to AAV5 ≥ 1:700
Inadequate renal function (creatinine clearance < 30 mL/min)
Liver function tests > 2× ULN or evidence of stage 3–4 cirrhosis without hepatologist clearance
Active infection, chronic or active hepatitis B or C without evidence of eradication, or immunosuppressive disorder including uncontrolled HIV

DocumentationNeutralizing antibody testing for AAV5 must be documented prior to treatment