CurrentPremera BluecrossPolicy 5.01.581

Pharmacologic Treatment of Hemophilia

Re-authorization criteria for non-formulary and formulary hemostasis/bleeding disorder agents (Alhemo, Hemlibra, Hympavzi, Qfitlia) allowing approval up to 12 months with documentation of positive clinical benefit; and repeat treatment of gene therapies Hemgenix and Roctavian is considered investigational.

Policy Summary

PayerPremera Bluecross

PolicyPharmacologic Treatment of Hemophilia

Policy CodePolicy 5.01.581

Change TypeUpdated coverage criteria & dosing; added/removed agents

Effective DateMar. 1, 2026

Next Review Date

Key ActionFor re-authorization of Alhemo, Hemlibra, Hympavzi, and Qfitlia, submit chart notes documenting decreased incidence of bleeding episodes to support approval up to 12 months.

SourceLink

POLICY UPDATE CHANGES

Non-formulary exception review authorizations for all drugs listed may be approved up to 12 months (2025 update).

Hympavzi (marstacimab-hncq) coverage criteria added (2025 update).

Hemgenix coverage criteria added/updated (2023 update) with specific eligibility bullets.

Roctavian coverage criteria added for adults with severe hemophilia A without pre-existing anti-AAV5 antibodies (2023 update).

Dosage/quantity limits updated for multiple agents (Alhemo, Hemlibra, Hympavzi, Qfitlia) with specific dosing regimens.

Coding entries for new HCPCS/J-codes for listed agents added (codes effective 2025/2026 as noted).

Added coverage criteria for Roctavian for adults with severe hemophilia A without pre-existing antibodies to AAV5.

Added Hemgenix coverage criteria for hemophilia B including criteria of life-threatening hemorrhage, repeated serious spontaneous bleeds, or current FIX prophylaxis (historical).

Added Beqvez (fidanacogene elaparvovec-dzkt) coverage criteria for hemophilia B (2024).

Added Hympavzi (marstacimab-hncq) coverage criteria for hemophilia A or B (2025).

Added coverage for Alhemo (concizumab-mtci) for individuals with hemophilia A and B with documented inhibitors (05/01/25).

Added coverage for Qfitlia (fitusiran) for hemophilia A and B (05/01/25).

Clarified non-formulary exception authorizations and re-authorization durations (2025 updates).

Updated dosing and quantity limits for multiple agents (2025-2026).

Removed Beqvez from policy (05/01/25).

Removed HCPCS code J3590 (03/01/26 history).

4Non-gene biologics eligible for 12-mo re-auth

2Gene therapies investigational for repeat tx

6Drugs discussed

12J/HCPCS codes listed

3Gene therapies referenced

Coverage Summary

Scope: This policy section covers re-authorization criteria for selected hemostasis agents and the investigational repeat‑treatment stance for specified gene therapies. It states that non‑formulary exception reviews and other reviews for Alhemo (concizumab‑mtci), Hemlibra (emicizumab‑kxwh), Hympavzi (marstacimab‑hncq), and Qfitlia (fitusiran) may be approved for up to 12 months when a positive clinical benefit/response is documented at re‑authorization (operationalized as chart notes documenting decreased incidence of bleeding episodes).

Coverage stance / status: Alhemo, Hemlibra, Hympavzi, and Qfitlia — eligible for re‑authorization up to 12 months contingent on documented benefit (chart notes showing decreased bleeding incidence). Hemgenix (etranacogene dezaparvovec‑drlb) and Roctavian (valoctocogene roxaparvovec‑rvox) — repeat treatment is considered investigational (not covered for repeat infusion).

High‑level actionable rule: For Alhemo, Hemlibra, Hympavzi, and Qfitlia, approvals (including non‑formulary exception approvals) may be extended up to 12 months at re‑authorization only if there is evidence of positive clinical benefit/response in the medical record (specifically chart documentation of decreased bleeding episodes). For Hemgenix and Roctavian, requests for repeat dosing/infusion are investigational and should not be approved under this policy.

Re-authorization & thresholds

Re-authorization durationUp to 12 months

Qfitlia antithrombin activity targetMaintain AT activity between 15–35%

Hympavzi maintenance dose rule300 mg weekly maintenance permitted only after 6 months at 150 mg weekly, patient ≥50 kg, and ≥2 documented breakthrough bleeds

Qfitlia quantity limitOne 20 mg vial or one 50 mg pen per month

Alhemo plasma conc. thresholdsPlasma conc. <200 ng/mL; 200–4,000 ng/mL; >4,000 ng/mL (dosing adjustments specified)

Medical Necessity — Authorization and Continuation Criteria

Continuation / re-authorization criteria for selected biologic and non-formulary agents (Alhemo, Hemlibra, Hympavzi, Qfitlia). Non-formulary exception rules are included.

Re-authorization for Alhemo, Hemlibra, Hympavzi, Qfitlia

Therapy is one of the following agents: Alhemo (concizumab-mtci), Hemlibra (emicizumab-kxwh), Hympavzi (marstacimab-hncq), or Qfitlia (fitusiran).
Positive clinical benefit/response is demonstrated at re-authorization (documentation required in chart notes).
Examples: reduced annual bleeding rate (ABR), fewer breakthrough bleeds, decreased need for on-demand factor/agents, improved patient-reported bleeding control.
Chart notes documenting decreased incidence of bleeding (provider must submit clinical notes summarizing bleeding frequency pre- and post-treatment).

Coding

HCPCS / J-codes listed in policyHCPCS

C9304	Injection, marstacimab-hncq (Hympavzi), 0.5 mg (code termed 07/01/25)
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)
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 / J-codes added or updated (history)HCPCS

Q9995	added then later terminated (historical)
J7170	added 01/01/19 (replaced Q9995)
J3590	added to report Hemgenix (later removed)
J1412	added 01/01/24
C9172	added 10/01/24
J1414	added 01/01/25
C9304	added 04/01/25
J7172	added 07/01/25 for Hympavzi (quarterly code update)
J7173	added 10/01/25
J7174	added 10/01/25

Drugs referenced in textmixed

Alhemo	concizumab-mtci
Hemlibra	emicizumab-kxwh
Hympavzi	marstacimab-hncq
Qfitlia	fitusiran
Hemgenix	etranacogene dezaparvovec-drlb - repeat treatment considered investigational
Roctavian	valoctocogene roxaparvovec-rvox - repeat treatment considered investigational

Provider Actions & Operational Notes

Prior Authorization

Authorization duration and re-authorization requirement

Authorization for Alhemo, Hemlibra, Hympavzi, and Qfitlia may be approved for up to 12 months. Re-authorization requires documentation of ongoing clinical benefit; submit chart notes that specifically document a decreased incidence of bleeding episodes compared with the period prior to initiation. For Hemlibra re-authorizations, approvals may be granted up to 12 months when the required documentation is provided.

Re-authorization approvals for Alhemo, Hemlibra, Hympavzi, and Qfitlia: up to 12 months
Chart notes must document decreased incidence of bleeding episodes and overall clinical benefit at each re-authorization request
Hemlibra re-authorization: may be approved up to 12 months with documentation of benefit

Documentation Required

Monitoring & documentation requirements for gene therapies

Background, Evidence & Definitions

Background excerpt (summary): The policy fragment explains re‑authorization logic for several hemostasis agents and reiterates that approvals for Alhemo (concizumab‑mtci), Hemlibra (emicizumab‑kxwh), Hympavzi (marstacimab‑hncq), and Qfitlia (fitusiran) may be granted for up to 12 months provided a positive clinical benefit/response is shown at re‑authorization (documented in chart notes as decreased bleeding episodes).

It also explicitly states that repeat treatment of the gene therapies Hemgenix (etranacogene dezaparvovec‑drlb) and Roctavian (valoctocogene roxaparvovec‑rvox) is considered investigational (repeat dosing not supported). The excerpt includes dosing/quantity and benefit assignment details for the listed agents and notes related administrative requirements (e.g., prescriber attestation, monitoring) in gene therapy coverage criteria.

Historical note: the policy history records that Beqvez (fidanacogene elaparvovec‑dzkt) was added in 2024 and subsequently removed in 05/01/25 when the manufacturer discontinued the product; thus Beqvez appears in the policy history but was later removed.

Study / Source	Key finding
EXPLORER 7 (Alhemo)	Mean ABR 1.7 (concizumab) vs 11.8 (no prophylaxis); rate ratio 0.14 (95% CI 0.07–0.29); P<0.001 (significant ABR reduction)
EXPLORER 8 (Alhemo)	Significant ABR reductions: 79% hemophilia B, 86% hemophilia A (large reductions vs on-demand treatment)
HAVEN 1 (Hemlibra)	Treated bleeding events 2.9 vs 23.3 (≈87% decrease); ABR all bleeds 5.5 vs 28.3 (≈80% decrease) versus no prophylaxis in inhibitor patients
HOPE-B (Hemgenix)	Mean FIX activity ≈39% at 6 months and 36.7% at 24 months; mean adjusted ABR reduced by 54% (from 4.1 to 1.9) post gene therapy
ATLAS-INH / ATLAS A/B (Fitusiran / Qfitlia)	Large ABR reductions vs comparators (e.g., ATLAS-INH mean ABR 1.7 vs 18.1; ATLAS A/B mean ABR 0.0 vs 21.8), significant prophylactic benefit
Roctavian (valoctocogene roxaparvovec)	Mean EEP ABR 2.6 vs baseline 5.4; non-inferiority met in Phase 3 single-dose trial in adults without pre-existing anti‑AAV5 antibodies
BASIS (Hympavzi)	ABR reductions: OD cohort 38 → 3.18; RP cohort 7.85 → 5.08 over 12 months after loading + weekly maintenance dosing; dose escalation to 300 mg allowed under criteria
Hemlibra prescribing information revision (supporting safety/label)	Label and evidence summaries updated (revised July 2025) documenting trial outcomes and dosing options
Alhemo / Hemlibra / Hympavzi / Qfitlia policy evidence summary	Policy references trials and dosing limits; re-authorization requires chart notes documenting decreased bleeding and approvals may be up to 12 months

Definitions

Positive clinical benefit/responseDocumented improvement (e.g., chart notes showing decreased incidence of bleeding episodes) at time of re-authorization

InvestigationalTreatment or repeat treatment not established/covered (e.g., repeat Hemgenix or Roctavian)

Revision History

01/01/19coding addition

HCPCS/J-code J7170 added to replace Q9995 for Hemlibra reporting (historic coding update).

01/01/24coding addition

HCPCS/J-code J1412 (Roctavian) added to coding.

2023coverage added (gene therapy)

Hemgenix coverage criteria added/updated (2023): eligibility requires severe/moderately severe hemophilia B plus ONE of life‑threatening hemorrhage, repeated serious spontaneous bleeds, or current FIX prophylaxis; requires discontinuation of FIX prophylaxis after administration and liver assessment prior to coverage.

Policy Summary

PayerPremera Bluecross

PolicyPharmacologic Treatment of Hemophilia

Policy CodePolicy 5.01.581

Change TypeUpdated coverage criteria & dosing; added/removed agents

Effective DateMar. 1, 2026

Next Review Date

Key ActionFor re-authorization of Alhemo, Hemlibra, Hympavzi, and Qfitlia, submit chart notes documenting decreased incidence of bleeding episodes to support approval up to 12 months.

SourceLink

On This Page

Prescribing provider is a hematologist or a prescriber who specializes in hemophilia (or treatment documented in consultation with such a specialist).

Maintenance dose does not exceed agent-specific quantity/dose limits (see Dosage and Quantity Limits node).

Re-authorization approval duration: up to 12 months for formulary and non-formulary approvals when above criteria are met.

Non-formulary exception — Re-authorization/Continuation

Non-formulary exception requests for Alhemo, Hemlibra, Hympavzi, or Qfitlia may be approved for up to 12 months when ALL of the following are met:
There is documentation of positive clinical benefit/response at the time of re-authorization.
Chart notes demonstrate decreased incidence of bleeding compared with baseline prior to therapy initiation.
Prescriber attests to providing requested clinical outcome information to the Company plan via the provider portal as applicable.

Repeat treatment of gene therapies (Not Medically Necessary / Investigational)

Repeat treatment of Hemgenix (etranacogene dezaparvovec-drlb) is considered investigational and not medically necessary.
Repeat treatment of Roctavian (valoctocogene roxaparvovec-rvox) is considered investigational and not medically necessary.
Repeat treatment of any other gene therapy for hemophilia not specified as an approved single-administration therapy is considered investigational.

Hemgenix coverage criteria (2023 update) - ONE of

Current or historical life-threatening hemorrhage.
Repeated, serious spontaneous bleeding episodes.
Currently receiving FIX prophylaxis (and will discontinue FIX prophylaxis following administration of Hemgenix).

Roctavian coverage criteria (2023 update)

Individual is an adult (aged 18 years or older).
Diagnosis of severe hemophilia A with factor VIII activity <1 IU/dL.
No pre-existing anti-AAV5 antibodies detected by an FDA-approved test (i.e., negative for anti-AAV5).
Factor VIII prophylaxis will be discontinued following administration of Roctavian if the individual is currently receiving prophylaxis.
Has received liver health assessment (ALT, AST, ALP, total bilirubin) and hepatic ultrasound and elastography; hepatology consult if radiological abnormalities or sustained enzyme elevations.
HIV negative or controlled HIV infection; no active hepatitis B or C; prescriber is hematologist or hemophilia specialist; patient education on alcohol abstinence and concomitant medication use provided.

Hympavzi updated indication and dosing (2026 update)

Indication: prophylaxis for individuals with hemophilia A without FVIII inhibitors OR hemophilia B without FIX inhibitors.
Age requirement: individual is aged 12 years or older.
Severity requirement: severe hemophilia A (FVIII activity <1%) OR moderately severe to severe hemophilia B (FIX activity ≤2%).
Maintenance dosing limit: standard maintenance dose limited to 150 mg weekly.
- Dose titration occurs after at least 6 months of treatment with Hympavzi 150 mg weekly.
- Individual weighs ≥50 kg (threshold: 50 kg).≥ 50 kg
- Documentation of ≥2 breakthrough bleeds while on 150 mg weekly.
Prescriber is a hematologist or specialist in hemophilia; will discontinue other prophylactic therapies before initiation; re-authorization requires documentation of clinical benefit.

Dosage and Quantity Limits (per agent)

Alhemo (concizumab-mtci): plasma concentration monitoring thresholds and quantity limits apply; re-authorization must confirm dosing consistent with prescribing information and any measured plasma concentration thresholds have been addressed in management.
Plasma concentration thresholds to be used operationally per lab guidance when available.
Hemlibra (emicizumab-kxwh): maintenance dose limited to one of the following dosing regimens: 1.5 mg/kg once weekly OR 3 mg/kg once every 2 weeks. Re-authorization requires documentation that maintenance dosing does not exceed these options.
Hympavzi (marstacimab-hncq): maintenance dose limited to 150 mg weekly, except dose increase to 300 mg weekly permitted only per Hympavzi updated indication and dosing criteria (see node above).
Qfitlia (fitusiran): initial/starting dose and antithrombin (AT) activity target must follow product labeling; re-authorization requires documentation of initial response and that on-treatment AT activity has not fallen below required safety thresholds (e.g., AT activity >= 60% as an eligibility baseline).AT activity >= 60% (baseline)
Qfitlia requires discontinuation of other prophylactic therapies prior to initiation and documentation of ≥2 breakthrough bleeds prior to initiation as per primary coverage criteria.

Investigational / Not Medically Necessary (summary)

Repeat treatment of Hemgenix and Roctavian is investigational and not medically necessary (see Repeat treatment of gene therapies node).
All other uses of Hemgenix or Roctavian beyond the indications outlined in this policy are considered investigational.
All other uses of Alhemo, Hemlibra, Hympavzi, and Qfitlia beyond indications in this policy are considered investigational.

For all gene therapy administrations the prescriber must attest to submitting clinical outcome data to the appropriate Company plan provider portal when requested. Hemgenix and Roctavian recipients require baseline and ongoing liver monitoring: obtain pre-treatment liver health assessment including ALT, AST, ALP, total bilirubin, hepatic ultrasound and elastography. If there are radiologic liver abnormalities or sustained enzyme elevations, a hepatology assessment is required prior to approval. After gene therapy administration, monitor liver enzymes and factor activity per FDA labeling and program guidance; document monitoring results in the medical record. If prophylactic factor replacement is discontinued post-gene therapy, document the clinical rationale and follow-up monitoring.

Prescriber attestation to provide clinical outcome information in the Company plan provider portal as requested
Hemgenix: pre-treatment liver health assessment (ALT, AST, ALP, total bilirubin), hepatic ultrasound, elastography
Hepatology assessment required if radiologic liver abnormalities or sustained liver enzyme elevations are present
Post-gene therapy monitoring: serial liver enzymes and factor activity per FDA prescribing information and program guidance; document results in chart
Document discontinuation of prophylactic factor replacement after gene therapy and clinical follow-up

Denial Risk

Repeat gene therapy not covered

Repeat administration of Hemgenix or Roctavian is considered investigational and is not covered. Requests for repeat gene therapy with Hemgenix or Roctavian should be denied as not medically necessary/investigational. Providers submitting requests for additional gene therapy doses should be informed that repeat treatment is outside of coverage.

Repeat gene therapy (Hemgenix) is investigational — repeat treatment not covered
Repeat gene therapy (Roctavian) is investigational — repeat treatment not covered
Repeat gene therapy requests for Hemgenix or Roctavian should be denied as investigational

Billing Rule

Billing & benefit assignment

Benefit assignment depends on the product and setting of care: some agents may be billed as a medical benefit when infused/ administered in a clinic or hospital (eg, Roctavian, Hemgenix) while others may be billed through the pharmacy benefit when dispensed to the patient (eg, Hemlibra, Alhemo, Hympavzi, Qfitlia) — verify plan-specific benefit rules. Product dosing and administration must follow the FDA-approved prescribing information; dose deviations require clinical justification. Use the appropriate J-codes/HCPCS for gene therapies and follow payer billing guidance for one-time gene therapy infusions.

Products may be medical benefit or pharmacy benefit depending on site of care and plan — verify benefit assignment
Adhere to FDA prescribing information for product dosing and administration; deviations require documentation
Use appropriate J-code/HCPCS billing for gene therapies and follow payer instructions for one-time infusion billing

ABRAnnualized Bleeding Rate

aPCCActivated prothrombin complex concentrate

Hemophilia A/BHemophilia A = congenital factor VIII deficiency; Hemophilia B = congenital factor IX deficiency

2023coverage added (gene therapy)

Roctavian coverage criteria added (2023) for adults with severe hemophilia A without pre‑existing anti‑AAV5 antibodies; requires discontinuation of FVIII prophylaxis after administration, liver assessment, and documentation of education on alcohol abstinence and concomitant meds.

05/01/24coverage added (gene therapy)

Beqvez (fidanacogene elaparvovec‑dzkt) coverage criteria added for hemophilia B (later removed).

03/01/25policy clarification

Non‑formulary exception review authorizations for all listed drugs clarified may be approved up to 12 months; Hemlibra re‑authorization updated to up to 12 months.

04/01/25coding addition

HCPCS code C9304 (Hympavzi injection, 0.5 mg) added to coding (effective 07/01/25 code term noted).

05/01/25coverage added

Alhemo (concizumab‑mtci) coverage expanded (05/01/25) to include individuals with hemophilia A or B with documented inhibitors; Qfitlia (fitusiran) added for hemophilia A and B; Beqvez removed from policy due to manufacturer discontinuation.

07/01/25coding addition

J7172 (marstacimab‑hncq / Hympavzi, 0.5 mg) added effective 07/01/25.

08/01/25dosage/quantity update

Quantity limits clarified for Alhemo, Hemlibra, and Hympavzi; Qfitlia quantity limit updated to one 20 mg vial or 50 mg pen monthly (Aug 2025).

10/01/25coding additions

New J‑codes J7173 (concizumab/Alhemo, 0.5 mg) and J7174 (fitusiran/Qfitlia, 0.04 mg) effective 10/01/25 added to coding list.

03/01/26coding removal / history

HCPCS code J3590 (previously used to report Hemgenix) removed from policy history.

03/01/26dosage/indication update (Hympavzi)Latest

Hympavzi coverage criteria clarified (2026): indication specified for hemophilia A without FVIII inhibitors or hemophilia B without FIX inhibitors; 300 mg weekly maintenance dose limit added with titration requirements after 6 months at 150 mg weekly, weight ≥50 kg, and documentation of ≥2 breakthrough bleeds.

2026coding additions (summary)Latest

Policy coding section lists HCPCS/J‑codes added across 2024–2026 including J1411 (Hemgenix therapeutic dose), J1412 (Roctavian), C9304 and J7172/ J7173/ J7174 for Hympavzi, Alhemo, and Qfitlia respectively (codes/effective dates documented in coding table).

05/01/25removal (product discontinued)

Beqvez removed from policy on 05/01/25 because the manufacturer discontinued the product.

07/01/25administrative requirement

From 07/01/25 updates: prescriber attestation requirement added for gene therapies (Roctavian, Hemgenix) to provide clinical outcome information via provider portal as requested by plan.

10/01/25coding additions

History records J7173 and J7174 added 10/01/25 as new codes for Alhemo (concizumab) and Qfitlia (fitusiran) respectively.

05/01/25dosage/quantity update

Qfitlia (fitusiran) quantity limit set to one 20 mg vial or 50 mg pen monthly (May–Aug 2025 updates documented).

07/01/25coding addition

C9304 listed in coding table with term date 07/01/25 for Hympavzi injection (0.5 mg) — coding history recorded.