CurrentPremera BluecrossPolicy 5.01.581

PHARMACY MEDICAL POLICY 5.01.581 Pharmacologic Treatment of Hemophilia

Defines medical necessity criteria, dosing/quantity limits, benefit application (medical vs pharmacy), coding, authorization durations, reauthorization requirements, investigational uses, prescriber attestation and monitoring requirements for specified pharmacologic treatments for hemophilia.

Policy Summary

PayerPremera Bluecross

PolicyPHARMACY MEDICAL POLICY 5.01.581 Pharmacologic Treatment of Hemophilia

Policy CodePolicy 5.01.581

Change TypeCoverage criteria additions and quantity/authorization clarifications (2025 updates)

Effective DateOct 1, 2025

Next Review Date

Key ActionMedications must be prescribed by or in consultation with a hematologist or a prescriber who specializes in hemophilia.

POLICY UPDATE CHANGES

Updated the re-authorization duration for Hemlibra to up to 12 months.

Added Hympavzi (marstacimab-hncq) coverage criteria for certain individuals with hemophilia A or B.

Clarified quantity limits for Alhemo, Hemlibra, and Hympavzi.

Updated Qfitlia quantity limit to one 20 mg vial or 50 mg pen monthly.

Updated Roctavian and Hemgenix coverage criteria to require prescriber attestation to provide clinical outcome information within the provider portal.

Added HCPCS code J7172 for Hympavzi (effective 07/01/25).

Added Alhemo (concizumab-mtci) and Qfitlia (fitusiran) coverage criteria; removed Beqvez (fidanacogene elaparvovec-dzkt) after manufacturer discontinued the product.

Clarified that non-formulary exception review authorizations for all drugs listed in this policy may be approved up to 12 months.

Multiple HCPCS code updates and additions over time (examples: Q9995, J7170, J3590, J1411, J1412, C9172, J1414, J7172, J7173, J7174).

6Drugs with coverage criteria in this part

2Gene therapies managed via medical benefit

>=12Minimum ages referenced (yrs)

2025-10-01Effective Date

12 monthsMax non-formulary approval duration

Coverage Summary

This policy takes a mixed coverage stance: it includes medical necessity criteria and quantity/dosing limits for multiple pharmacologic agents (Alhemo, Hemlibra, Hympavzi, Qfitlia) and two AAV vector gene therapies (Hemgenix, Roctavian). Policy number is 5.01.581 and the policy is effective 2025-10-01 with last review 2025-09-09. Benefit application: Alhemo, Hemlibra, Hympavzi, and Qfitlia may be managed through the pharmacy or medical benefit, while Hemgenix and Roctavian are managed through the medical benefit. Authorization durations: non-formulary exception review authorizations may be approved for up to 12 months; Hemgenix and Roctavian are authorized as a one-time infusion per policy and reauthorizations for Alhemo, Hemlibra, Hympavzi, and Qfitlia may be approved up to 12 months when clinical benefit/response is documented.

Key facts (compact)

Effective Date2025-10-01

Policy Number5.01.581

Managed via medical benefitGene therapies managed via medical benefit: 2 (Hemgenix, Roctavian)

Max non-formulary approval durationNon-formulary exception reviews may be approved up to 12 months

Minimum referenced ages>=12 years (policy lists minimum age 12 for multiple products; gene therapies require >=18 years)

Initial Therapy Criteria — Medical Necessity

Alhemo (concizumab-mtci) — Medical Necessity

Alhemo (concizumab-mtci) may be considered medically necessary when ALL of the following criteria are met:

ALL of the following

The individual is aged 12 years or older
Was assigned male at birth
Has been diagnosed with hemophilia A (congenital factor VIII deficiency) or hemophilia B (congenital factor IX deficiency) with or without factor VIII or factor IX inhibitors
Severity requirement
- Has severe hemophilia A (congenital factor VIII deficiency) with factor VIII activity less than 1%

Continuation / Reauthorization Criteria

Investigational / Not Covered Uses

Applicable Codes

HCPCS / J-codes listedHCPCS

C9304	Injection, marstacimab-hncq (Hympavzi), 0.5 mg
J1411	Injection, etranacogene dezaparvovec-drlb, per therapeutic dose (Hemgenix)
J1412	Injection, valoctocogene roxaparvovec-rvox; per ml; containing nominal 2 x 10^13 vector genomes (Roctavian)
J3590	Unclassified biologics (use to report: Alhemo, Qfitlia)
J7170	Injection, emicizumab-kxwh (Hemlibra), 0.5 mg
J7172	Injection, marstacimab-hncq (Hympavzi), 0.5 mg (new code effective 07/01/25)
J7173	Injection, concizumab-mtci (Alhemo), 0.5 mg (new code effective 10/01/25)
J7174	Injection, fitusiran (Qfitlia), 0.04 mg (new code effective 10/01/25)

HCPCS codes referenced/added in historyHCPCS

Q9995	Historical HCPCS code added then removed (mentioned in policy history)
J7170	HCPCS code added 01/01/19 (replaced Q9995)
J3590	Code used to report Hemgenix (added 05/01/23)
J1411	Added for Hemgenix (history note)
J1412	Coding added 01/01/24
C9172	Coding update added 10/01/24
J1414	Coding update added 01/01/25
J7172	HCPCS code for Hympavzi added 07/01/25
J7173	New HCPCS code added effective 10/01/25 (history)
J7174	New HCPCS code added effective 10/01/25 (history)

Provider Actions & Authorization Requirements

Prior Authorization

Prescriber specialty requirement

Medications referenced in this policy must be prescribed by, or in documented consultation with, a hematologist or a provider who specializes in hemophilia care. This requirement applies to initial authorization and reauthorization requests.

Affected products: Alhemo, Hemgenix, Hemlibra, Hympavzi, Qfitlia, Roctavian

Prior Authorization

Authorization durations / Non‑formulary exception

Non‑formulary exception requests may be approved for up to 12 months. Gene therapies (Hemgenix and Roctavian) are authorized only as single (one‑time) administrations. Reauthorization for non‑gene therapy agents may be approved up to 12 months when there is documented positive clinical benefit; specific agents (e.g., Hemlibra, Alhemo, Hympavzi, Qfitlia) follow standard reauthorization review timelines.

Clinical Evidence Highlights

1.7 vs 11.8Alhemo EXPLORER-7 mean ABR: 1.7 vs 11.8 (rate ratio 0.14; 95% CI 0.07-0.29; P<0.001)

39% / 36.7%Hemgenix HOPE-B mean FIX activity: 39% at 6 months; 36.7% at 24 months — mean adjusted ABR reduced 54% (7–18 months)

2.9 vs 23.3Hemlibra HAVEN 1 treated bleeding ABR: 2.9 vs 23.3 events (87% decrease; p<0.001)

1.7 vs 18.1Qfitlia ATLAS‑INH mean ABR: 1.7 vs 18.1 (90.8% reduction; p<0.0001)

Evidence sources cited in the policy include pivotal trials and reviews such as HOPE‑B (Hemgenix), EXPLORER 7 and EXPLORER 8 (Alhemo/concizumab), HAVEN 1 (Hemlibra), and ATLAS INH (Qfitlia/fitusiran), as well as guideline and value-assessment documents (WFH, NHF/MASAC, and the ICER report). Full bibliographic references and trial details are provided in the policy references section of the source document.

Background

Background and scope: this policy covers pharmacologic treatments for hemophilia A and B including monoclonal antibody therapies (e.g., emicizumab/Hemlibra), anti‑TFPI monoclonal antibodies (e.g., concizumab/Alhemo, marstacimab/Hympavzi), an siRNA therapy (fitusiran/Qfitlia), and AAV vector gene therapies (etranacogene dezaparvovec/Hemgenix and valoctocogene roxaparvovec/Roctavian).

Key clinical factors considered in coverage determinations include age (minimum ages specified per product), sex assignment at birth (most criteria reference individuals assigned male at birth), disease severity by factor activity (e.g., FVIII <1% for severe hemophilia A; FIX ≤2% for severe/moderately severe hemophilia B), inhibitor status (Nijmegen‑Bethesda assay thresholds noted for FIX inhibitors), and liver health/viral infection status for gene therapy candidates (required liver enzyme testing, ultrasound/elastography, and hepatology assessment as indicated).

Prior to initiating listed agents, the policy requires discontinuation of other prophylactic hemophilia therapies as specified for several products (for example, discontinuing FIX or FVIII prophylaxis after Hemgenix or Roctavian, and stopping other prophylactic therapies before starting Alhemo or Qfitlia). Prescriber specialty requirements and documentation of medical necessity are also required.

Definitions (brief)

Severe hemophilia AFactor VIII activity less than 1% (policy also states <1 IU/dL for Roctavian)

Severe / moderately severe hemophilia B

Dosing, Quantity Limits & Thresholds

This section summarizes dosing thresholds and quantity limits referenced elsewhere in the policy; it is not a substitute for the FDA-approved prescribing information. See the product labeling for full prescribing details.

Threshold / Dosing	Value / Notes
Alhemo plasma concentration-based dosing thresholds	<200 ng/mL -> adjust to 0.25 mg/kg once daily; 200–4,000 ng/mL -> continue 0.2 mg/kg once daily; >4,000 ng/mL -> adjust (documented dose adjustment noted)
Hemgenix / Hemophilia B severity	Plasma FIX activity ≤ 2% required for Hemgenix eligibility
Hemlibra maintenance dosing options	Maintenance limited to one of: 1.5 mg/kg once weekly OR 3 mg/kg every 2 weeks OR 6 mg/kg every 4 weeks
Hympavzi dosing (loading + maintenance)	300 mg loading dose, followed by 150 mg once weekly
Qfitlia maintenance dose and updated quantity limit	Maintenance dose 150 mg weekly; quantity limit updated to one 20 mg vial OR one 50 mg pen monthly
Roctavian severity threshold	Factor VIII activity < 1 IU/dL required for Roctavian eligibility
Non-formulary exception / authorization duration	Non-formulary exception reviews for listed drugs may be approved up to 12 months; reauthorization for certain agents (e.g., Hemlibra) may be approved up to 12 months
Qfitlia quantity limit (alternate note)	Policy explicitly notes updated Qfitlia quantity limit: one 20 mg vial or 50 mg pen monthly (2025 update)

Revision History

03/01/25added

Added Hympavzi (marstacimab-hncq) coverage criteria (annual review approved 02/11/2025).

07/01/25coding

Added HCPCS code J7172 for Hympavzi (marstacimab-hncq) (quarterly code update).

05/01/25added

Added Alhemo (concizumab-mtci) and Qfitlia (fitusiran) coverage criteria (interim review approved 04/08/2025); removed Beqvez (fidanacogene elaparvovec-dzkt) after manufacturer discontinued the product.

Policy Summary

PayerPremera Bluecross

PolicyPHARMACY MEDICAL POLICY 5.01.581 Pharmacologic Treatment of Hemophilia

Policy CodePolicy 5.01.581

Change TypeCoverage criteria additions and quantity/authorization clarifications (2025 updates)

Effective DateOct 1, 2025

Next Review Date

Key ActionMedications must be prescribed by or in consultation with a hematologist or a prescriber who specializes in hemophilia.

On This Page

Moderately severe to severe hemophilia B (congenital factor IX deficiency) with factor IX activity less than or equal to 2%<= 2%

Will discontinue use of other prophylactic therapies of hemophilia before initiation of Alhemo (concizumab-mtci)

Medication is being prescribed by or in consultation with a hematologist or a prescriber who specializes in hemophilia

Hemgenix (etranacogene dezaparvovec-drlb) — Medical Necessity

Hemgenix (etranacogene dezaparvovec-drlb) may be considered medically necessary for adults when ALL of the following criteria are met:

ALL of the following

The individual is aged 18 years or older
Was assigned male at birth
Has severe or moderately severe hemophilia B as defined by a plasma Factor IX (FIX) activity level of 2% or less<= 2%
Bleeding or prophylaxis requirement (MEET ONE)
- Current or historical life-threatening hemorrhage
- Repeated, serious spontaneous bleeding episodes
- Is currently receiving FIX prophylaxis
If the individual is currently receiving FIX prophylaxis, FIX prophylaxis will be discontinued following administration of Hemgenix
The individual does not have a history of FIX inhibitors or a positive screen result of 0.6 or greater Bethesda Units (BU) using the Nijmegen-Bethesda assay< 0.6 BU
Liver assessment requirements
- Has received a liver health assessment including enzyme testing [alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin]
- Has received a hepatic ultrasound and elastography
- A hepatologist has assessed the individual if the individual has radiological liver abnormalities or sustained liver enzyme elevations
Medication is being prescribed by or in consultation with a hematologist or a prescriber who specializes in hemophilia B
The individual does not have a history of receiving gene therapy and is not under consideration for treatment with another gene therapy for hemophilia B
Is human immunodeficiency virus (HIV) negative or has a controlled HIV infection
Does not have an active hepatitis B or hepatitis C infection

Hemlibra (emicizumab-kxwh) — Medical Necessity

Hemlibra (emicizumab-kxwh) may be considered medically necessary for adults and pediatric individuals when ALL of the following criteria are met:

ALL of the following

Diagnosis of hemophilia A (congenital factor VIII deficiency) with or without factor VIII inhibitors
Hemlibra is not used concurrently with high dose activated prothrombin complex concentrate (aPCC)
Maintenance dose options (select ONE)
- 1.5 mg/kg once weekly
- 3 mg/kg once every two weeks
- 6 mg/kg once every four weeks

Hympavzi (marstacimab-hncq) — Medical Necessity

Hympavzi (marstacimab-hncq) may be considered medically necessary when ALL of the following criteria are met:

ALL of the following

The individual is aged 12 years or older
Has been diagnosed with hemophilia A (congenital factor VIII deficiency) or hemophilia B (congenital factor IX deficiency)
Severity requirement
- Has severe hemophilia A (congenital factor VIII deficiency) with factor VIII activity less than 1%< 1%
- Moderately severe to severe hemophilia B (congenital factor IX deficiency) with factor IX activity less than or equal to 2%<= 2%
Has no documented history or presence of factor VIII or IX inhibitors
Will discontinue use of other prophylactic therapies such as factor products or Hemlibra (emicizumab-kxwh)
Medication is being prescribed by or in consultation with a hematologist or a prescriber who specializes in hemophilia

Qfitlia (fitusiran) — Medical Necessity

Qfitlia (fitusiran) may be considered medically necessary when ALL of the following criteria are met:

ALL of the following

The individual is aged 12 years or older
Was assigned male at birth
Has been diagnosed with hemophilia A (congenital factor VIII deficiency) or hemophilia B (congenital factor IX deficiency)
Severity requirement
- Has severe hemophilia A (congenital factor VIII deficiency) with factor VIII activity less than 1%< 1%
- Moderately severe to severe hemophilia B (congenital factor IX deficiency) with factor IX activity less than or equal to 2%<= 2%
Has at least 6 bleeding episodes requiring on-demand agents within the prior 6 months>= 6 bleeds in 6 months
Does not have antithrombin activity less than 60%>= 60%
Will discontinue use of other prophylactic therapies of hemophilia before initiation of Qfitlia (fitusiran)
Medication is being prescribed by or in consultation with a hematologist or a prescriber who specializes in hemophilia
Maintenance dose is limited to 150 mg once weekly

Roctavian (valoctocogene roxaparvovec-rvox) — Medical Necessity

Roctavian (valoctocogene roxaparvovec-rvox) may be considered medically necessary when ALL of the following criteria are met:

ALL of the following

The individual is aged 18 years or older
Was assigned male at birth
Diagnosis of severe hemophilia A (congenital factor VIII deficiency) with factor VIII activity less than 1 IU/dL< 1 IU/dL
Factor VIII prophylaxis will be discontinued following administration of Roctavian if the individual is currently receiving factor VIII prophylaxis
The individual does not have pre-existing antibodies to adeno-associated virus serotype 5 detected by an FDA-approved test
Liver assessment and documentation
- Has received a liver health assessment including enzyme testing [alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin]
- Has received a hepatic ultrasound and elastography
- Documentation is provided demonstrating that the individual received education relating to alcohol abstinence and the use of concomitant medications
Is human immunodeficiency virus (HIV) negative or has a controlled HIV infection
Does not have an active hepatitis B or hepatitis C infection
Prescriber attests to providing clinical outcome information within the appropriate provider portal as requested by the manufacturer or registry
Medication is being prescribed by or in consultation with a hematologist or a prescriber who specializes in hemophilia A

Non‑formulary exception approval duration: up to 12 months
Hemgenix and Roctavian: one‑time infusion authorization only
Reauthorization: up to 12 months for appropriate agents with demonstrated clinical benefit

Documentation Required

Medical record documentation requirements

Initial authorization requires submission of chart notes documenting the diagnosis and meeting of applicable policy criteria. Reauthorization requests must include clinical progress notes demonstrating ongoing benefit; for Alhemo, Hemlibra, Hympavzi, and Qfitlia this should include documentation of decreased incidence of bleeding episodes or other objective measures of clinical response.

Initial: chart notes documenting diagnosis and that all initial criteria are met
Reauthorization: progress notes documenting clinical response (e.g., reduced bleeding frequency) for Alhemo, Hemlibra, Hympavzi, Qfitlia

Documentation Required

Liver assessment & hepatology consultation

A comprehensive liver assessment is required for Hemgenix and Roctavian candidates and includes laboratory and imaging evaluation. If radiologic abnormalities or sustained enzyme elevations are present, a hepatology consultation is required prior to authorization.

Required liver tests: ALT, AST, alkaline phosphatase (ALP), and total bilirubin
Required imaging: hepatic ultrasound and elastography
Hepatologist assessment: required if hepatic ultrasound/elastography show abnormalities or if there are sustained elevations in liver enzymes prior to Hemgenix or Roctavian consideration

Documentation Required

Inhibitor and antibody testing

Pre‑treatment inhibitor and antibody testing is required for gene therapy eligibility. Specific assay thresholds and FDA‑approved test results must be documented in the record.

Hemgenix: Nijmegen‑Bethesda assay for FIX inhibitors must be negative; threshold for exclusion is ≥ 0.6 Bethesda Units (BU)
Roctavian: documentation of negative pre‑existing anti‑AAV5 antibodies by an FDA‑approved test is required

Documentation Required

Prescriber attestation for gene therapies

Prescribers of Hemgenix and Roctavian must attest that they will provide requested clinical outcome information through the designated provider portal. For Roctavian, prescriber documentation must also confirm that the patient received education about alcohol abstinence and avoidance or careful management of concomitant hepatotoxic medications.

Attestation: prescriber must commit to submitting clinical outcome data via the appropriate provider portal for Hemgenix and Roctavian
Roctavian education requirement: documentation that the patient received education on alcohol abstinence and on the management/avoidance of concomitant medications that could affect liver health

Billing Rule

Benefit application

Benefit application may vary by product — follow the specified benefit pathway and adhere to FDA dosing/quantity limits.

Pharmacy or medical benefit (may be managed under either depending on plan): Alhemo, Hemlibra, Hympavzi, Qfitlia
Medical benefit only: Hemgenix, Roctavian
Adhere to FDA‑approved dosing and quantity limits for each product

Denial Risk

Repeat gene therapy

Repeat administration of Hemgenix or Roctavian is considered investigational and will not be approved.

Repeat gene therapy (Hemgenix, Roctavian): investigational — not approvable

Denial Risk

Discontinue prophylaxis after gene therapy

Coverage for gene therapy candidates is contingent upon discontinuation of factor prophylaxis (FIX for Hemgenix; FVIII for Roctavian) following administration. Continued prophylactic factor therapy post‑gene therapy may affect coverage determinations and could lead to denial.

Hemgenix: FIX prophylaxis must be discontinued following administration if previously used
Roctavian: FVIII prophylaxis must be discontinued following administration if previously used

Factor IX activity less than or equal to 2%

Bethesda Unit (BU)Measure of inhibitor titer; policy uses Nijmegen-Bethesda assay with positive screen >= 0.6 BU for FIX inhibitors

Hemgenix (definition)Etranacogene dezaparvovec-drlb: AAV vector–based gene therapy for hemophilia B with specific coverage and post-administration requirements

Roctavian (definition)Valoctocogene roxaparvovec-rvox: AAV vector–based gene therapy for hemophilia A limited to adults without pre-existing anti-AAV5 antibodies with post-administration requirements

08/01/25clarified

Clarified quantity limits for Alhemo, Hemlibra, and Hympavzi; updated Qfitlia quantity limit to one 20 mg vial or 50 mg pen monthly (interim review approved July 8, 2025).

10/01/25codingLatest

Added new HCPCS codes J7173 (concizumab/Alhemo) & J7174 (fitusiran/Qfitlia) effective 10/01/25 and other coding updates (added C9172 earlier; multiple HCPCS updates over time).

03/01/25revised

Updated re-authorization duration for Hemlibra (emicizumab-kxwh) to up to 12 months.

03/01/25clarified

Clarified that non-formulary exception review authorizations for all drugs listed in this policy may be approved up to 12 months and that listed medications are subject to the product's FDA dosing and administration.

11/14/23 (effective 03/07/24)clarified

Updated Hemgenix coverage criteria to require discontinuation of FIX prophylaxis post-administration and hepatology assessment if radiological liver abnormalities or sustained liver enzyme elevations (approved 11/14/23, effective 03/07/24).

10/01/23added

Added coverage criteria for Roctavian (valoctocogene roxaparvovec-rvox) for adults with severe hemophilia A without pre-existing anti-AAV5 antibodies.

08/01/25revised

Updated Roctavian and Hemgenix coverage criteria to require prescriber attestation to provide clinical outcome information within the provider portal (clarified July/August 2025 history).