ModifiedUnitedHealthcarePolicy CS2025D0047E

Factor Mimetics and Rebalancing Agents for Hemophilia

Medical benefit drug policy governing coverage criteria for factor mimetics and rebalancing agents (emicizumab, concizumab, marstacimab, fitusiran) for prophylaxis in hemophilia A and B for UnitedHealthcare members; includes initial and continuation authorization requirements and dosing per FDA labeling.

Policy Summary

PayerUnitedHealthcare

PolicyFactor Mimetics and Rebalancing Agents for Hemophilia

Policy CodePolicy CS2025D0047E

Change TypeCoverage criteria revised

Effective DateNov 1, 2025

Next Review Date

Key ActionObtain prior authorization and document age, hemophilia type, inhibitor titer (Bethesda units), prior therapy, and positive clinical response to support approval.

SourceLink

POLICY UPDATE CHANGES

Revised coverage criteria for concizumab-mtci (Alhemo); added criterion to allow coverage when the patient has a diagnosis of hemophilia A and has not developed high-titer factor VIII/IX inhibitors (>= 5 Bethesda units).

4named products referenced

12authorization period (months)

>=5 BUhigh-titer inhibitor threshold

>=12 yrsage indication (most agents)

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J7170-J7174, D66-D67

Coverage Criteria for Factor Mimetics and Rebalancing Agents

Agent-specific initial and continuation therapy criteria

Medically necessary when ALL of the following agent-specific criteria are met (each agent has separate initial and continuation criteria):

Agent-specific initial therapy general requirements: Diagnosis of hemophilia A or B as specified for the agent; age requirement as specified for the agent (typically >= 12 years for most agents; Hemlibra has provisions for younger children); prescribed for routine prophylaxis to prevent or reduce frequency of bleeding episodes; dosing per U.S. FDA labeled dosing; authorization for no more than 12 months; one of: patient cannot self-inject and has no caretaker who can be trained OR patient receives the agent from a contracted hemophilia treatment center; inhibitor-status criteria as specified for the individual agent (see inhibitor-status nodes).

Each agent (Alhemo, Hemlibra, Hympavzi, Qfitlia) lists its own combinations of diagnosis, inhibitor status, age, and administration/setting requirements.

Inhibitor status options for initial therapy

Without high-titer inhibitor: Diagnosis of hemophilia (A or B, per agent indication) AND patient has not developed high-titer factor VIII or IX inhibitors (i.e., has not developed inhibitors >= 5 Bethesda units (BU)).>= 5 BU
Applies to agents indicated only for patients without inhibitors (e.g., Hympavzi in its labeled indications).
With high-titer inhibitor: Diagnosis of hemophilia (A or B, per agent indication) AND patient has developed high-titer factor VIII or IX inhibitors (i.e., inhibitors >= 5 Bethesda units (BU)).>= 5 BU
Applies to agents indicated for use in patients with inhibitors (e.g., Alhemo and Hemlibra in indicated populations).

Continuation therapy general requirements: Patient has previously been treated with the agent; prescribed for routine prophylaxis to prevent or reduce frequency of bleeding episodes; documentation of positive clinical response to therapy; one of: patient cannot self-inject and has no caretaker who can be trained OR patient receives the agent from a contracted hemophilia treatment center; dosing per U.S. FDA labeled dosing; authorization for no more than 12 months.

Continuation criteria mirror initial therapy but require documented positive clinical response.

Hemlibra (emicizumab-kxwh) age and administration specifics: For initial therapy: diagnosis of hemophilia A (per FDA labeling), prescribed for routine prophylaxis, and one of: patient is less than 7 years of age; or patient is 7 years of age or older and cannot self-inject and does not have a caretaker who can be trained; or patient is receiving Hemlibra from a contracted hemophilia treatment center. Hemlibra continuation requires prior Hemlibra treatment and documentation of positive clinical response.

Hemlibra is indicated for patients newborn and older per FDA labeling and the policy provides specific age-based allowances for administration.

Agent-specific coverage aligned to FDA labels and policy revisions

Covered when agent is FDA-indicated and patient meets age and inhibitor-status indications as described in the FDA labeling and updated policy criteria.

Alhemo (concizumab-mtci) coverage: Routine prophylaxis for patients 12 years of age and older with hemophilia A or B, with or without inhibitors per FDA indication; policy revision added an allowance clarifying coverage when a patient with hemophilia A has not developed high-titer factor VIII/IX inhibitors (i.e., has not developed inhibitors >= 5 BU).age >= 12 years; for the revised allowance: inhibitor titer < 5 BU

Warnings include thromboembolic events and hypersensitivity; common adverse reactions include injection site reactions and urticaria.

Hympavzi (marstacimab-hncq) coverage: Routine prophylaxis for patients 12 years of age and older with hemophilia A or B without factor VIII or IX inhibitors (per FDA labeling).age >= 12 years; no inhibitors

Efficacy established in BASIS study; common adverse reactions include injection site reaction, headache, and pruritus.

This policy does not apply to all U.S. jurisdictions. Refer to the state-specific policy or guideline where noted for coverage determinations in: Arizona, Indiana, Kansas, Louisiana, North Carolina, Ohio (see Ohio-only policy: Factor Mimetics and Rebalancing Agents for Hemophilia), Pennsylvania (refer to the state’s Medicaid clinical policy), and Virginia.

The fixed-dose regimen of Qfitlia (fitusiran) that was evaluated in early randomized studies is not approved because it led to excessive clotting in some patients; the approved regimen uses antithrombin-based (adjustable) dosing guided by periodic antithrombin measurements.

The list of procedure and diagnosis codes in this policy is provided for reference only. Inclusion of a code does not imply that the corresponding service is covered or guarantee reimbursement; benefit coverage is determined by federal, state, and contractual requirements as well as applicable laws, and other policies or guidelines may apply.

Billing and Diagnosis Codes

Covered HCPCS/J-codes (listed for reference)HCPCS

J7170	Injection, emicizumab-kxwh, 0.5 mg
J7172	Injection, marstacimab-hncq, 0.5 mg
J7173	Injection, concizumab-mtci, 0.5 mg
J7174	Injection, fitusiran, 0.04 mg

Relevant ICD-10 diagnosis codes (listed for reference)ICD-10

D66	Hereditary factor VIII deficiency
D67	Hereditary factor IX deficiency

inv-08: High-titer inhibitor cutoff — clinical threshold

High-titer inhibitor cutoff>= 5 Bethesda units (BU)

Applies to factor VIII and IX inhibitorsDefinition references both factor VIII and factor IX inhibitor titers as measured in BU

Used for agent-specific eligibilityThreshold used to determine eligibility for agents that are indicated for patients with or without high-titer inhibitors (see agent criteria)

inv-09: Inhibitor titer threshold (Bethesda units) — reiterated threshold value

Inhibitor titer threshold (Bethesda units)>= 5 BU

Referenced in policy revisionRevision added criterion specifying >= 5 BU for concizumab (Alhemo) coverage rationale

Prior Authorization, Documentation, and Operational Guidance

Prior Authorization

Prior Authorization Required

Prior authorization is required for prophylactic rebalancing agents listed in this policy (e.g., Alhemo, Hemlibra, Hympavzi, Qfitlia, and related agents) when prescribed for routine prophylaxis to prevent or reduce bleeding episodes. Requests should reference the agent-specific coverage criteria in this policy and include the documentation elements listed below.

Affected agents/codes: Alhemo (concizumab-mtci), Hemlibra (emicizumab-kxwh), Hympavzi (marstacimab-hncq), Qfitlia (fitusiran)
Prior authorization required for initiation and continuation of routine prophylaxis (authorization determinations must reference agent-specific criteria)

Prior Authorization

Prior Authorization — Agent-Specific Determinations

Authorization determinations for prophylactic rebalancing agents should reference the specific agent criteria (initial vs continuation therapy, age limits, inhibitor status) in this policy. For agents where coverage depends on inhibitor status, ensure the determination reflects whether the patient has high-titer inhibitors (>= 5 BU) as specified in the agent criteria.

Decision-makers should use the applicable initial and continuation therapy branches for each agent

Clinical Background and Mechanisms

This policy addresses several classes of hemostasis agents used for routine prophylaxis in hemophilia A and B, including TFPI antagonists (for example, concizumab/Alhemo and marstacimab/Hympavzi), a bispecific FIXa/FX antibody (emicizumab/Hemlibra), and an antithrombin-directed therapy (fitusiran/Qfitlia). These agents are used to reduce bleeding frequency in patients with or without factor VIII or IX inhibitors and have agent-specific indications, dosing, and safety considerations described in the FDA labeling and in this policy.

Key Definitions

inv-19: Definition of high-titer inhibitor (>= 5 BU)

Definition of high-titer inhibitorPresence of factor VIII or IX inhibitors greater than or equal to 5 Bethesda units (BU)

Clinical relevanceHigh-titer status informs eligibility for certain rebalancing agents and prophylaxis options

Not induced by concizumabConcizumab effect is not influenced by presence of inhibitory antibodies to FVIII or FIX; concizumab does not induce direct inhibitors to FVIII or FIX

inv-20: Definition of routine prophylaxis

Routine prophylaxis — definitionUse of a prophylactic agent to prevent or reduce the frequency of bleeding episodes in patients with hemophilia

Age-based indicationsFDA indications for routine prophylaxis vary by agent (e.g., Alhemo, Hympavzi, Qfitlia: 12 years and older; Hemlibra: newborn and older)

Policy Revision History

2025-11-01Revised coverage criteriaLatest

Revised coverage criteria for concizumab-mtci (Alhemo) adding a criterion to allow coverage when the patient has hemophilia A and has not developed high-titer factor VIII/IX inhibitors (>= 5 Bethesda units).

2025-11-01Policy history entry

Updated supporting sections (Clinical Evidence, FDA, References) and archived previous policy version CS2025D0047D as noted in the policy history revision information.

Policy Summary

PayerUnitedHealthcare

PolicyFactor Mimetics and Rebalancing Agents for Hemophilia

Policy CodePolicy CS2025D0047E

Change TypeCoverage criteria revised

Effective DateNov 1, 2025

Next Review Date

Key ActionObtain prior authorization and document age, hemophilia type, inhibitor titer (Bethesda units), prior therapy, and positive clinical response to support approval.

SourceLink

On This Page

Qfitlia (fitusiran) coverage: Routine prophylaxis for patients 12 years of age and older with hemophilia A or B with or without factor VIII or IX inhibitors using the approved antithrombin-based dosing regimen; fixed-dose Qfitlia is not approved due to excessive clotting risk.age >= 12 years; antithrombin-based dosing required

Efficacy: substantial reductions (approximately 71–73%) in estimated annualized bleeding rate versus on-demand controls; monitor antithrombin activity.

Hemlibra (emicizumab-kxwh) coverage: Routine prophylaxis for patients with hemophilia A (newborn and older) with or without factor VIII inhibitors per FDA labeling.age newborn and older; hemophilia A diagnosis

Associated with lower bleeding rates compared to no prophylaxis; policy includes specific age/administration allowances (see criteria).

Measurement requirementProviders should document Bethesda unit measurement when reporting inhibitor status

Include inhibitor-related criteria where present (e.g., agent coverage limited to patients without high-titer factor VIII/IX inhibitors)

Step Therapy

Step Therapy Guidance

This policy defines initial versus continuation therapy criteria for listed agents but does not impose additional step-therapy trials beyond the agent-specific requirements. Review the policy's initial and continuation sections for each agent to determine applicable requirements for authorization.

Policy distinguishes initial therapy (new starts) and continuation therapy (documented prior benefit) but does not mandate specific prior product trials as a universal step requirement

Note

NHF-Referenced Treatment Options — Context for Sequencing

The National Hemophilia Foundation (NHF) treatment guidance is referenced for clinical context and sequencing of therapies. NHF recommendations identify conventional factor replacement (recombinant or plasma-derived products) and other established therapies (e.g., desmopressin for mild hemophilia A) as treatment options; newer rebalancing agents and monoclonal/bispecific antibodies are noted as recommended or appropriate in specific circumstances. Use NHF guidance to inform clinical sequencing and alternatives when making coverage decisions.

NHF lists recombinant and prolonged-half-life factor concentrates as treatment of choice for hemophilia A and B
NHF recommends consideration of Hemlibra and other agents in appropriate clinical contexts; consult NHF guidance for sequencing and alternatives

Documentation Required

Required Clinical Documentation for Continuation

For continuation (renewal) authorizations, submit documentation showing prior treatment with the requested agent and evidence of positive clinical response (e.g., reduced bleeding frequency, fewer factor infusions, improved bleed control). Ensure dosing follows FDA-labeled recommendations and include evidence supporting ongoing clinical benefit.

Documentation of prior treatment with the requested agent
Evidence of positive clinical response (clinical notes, bleed logs, infusion records)
Dosing consistent with U.S. FDA-labeled dosing

Documentation Required

Required Clinical Documentation — Initial Authorization

Required documentation for initial authorizations must include patient age, confirmed hemophilia diagnosis (A or B), and inhibitor status with titer levels when relevant. For agents with inhibitor-related coverage criteria, provide laboratory documentation of inhibitor presence and titer (Bethesda units) to determine eligibility under the policy.

Patient age and diagnosis (hemophilia A or B)
Inhibitor testing results and titer (provide Bethesda unit value) when coverage criteria reference high-titer status (>= 5 BU)
For patients unable to self-inject, documentation that no suitable caregiver can be trained, or that treatment will be provided via a contracted hemophilia treatment center

Prior Authorization

Authorization Duration and Dosing

Authorizations are issued for up to 12 months for routine prophylaxis and must follow U.S. Food and Drug Administration labeled dosing for the specific agent. Renewal requests should document continued clinical benefit and adherence to labeled dosing; exceptions to pharmacy vs physician benefit routing are noted within agent-specific criteria.

Standard authorization period: up to 12 months
Dosing requirement: follow FDA-labeled dosing for the specific agent
Benefit routing: many agents are self-injectable and expected to be obtained via pharmacy benefit unless policy conditions are met

Note

Revision May Affect Authorization Determinations

Policy revisions effective 11/01/2025 added an inhibitor-related coverage criterion (allowing coverage when the patient has a diagnosis of hemophilia A and has not developed high-titer factor VIII/IX inhibitors [>= 5 BU]). Review prior authorization decisions made before this revision — determinations may change when inhibitor-status criteria now permit coverage.

Revision added criterion: coverage allowed when patient with hemophilia A has not developed high-titer factor VIII/IX inhibitors (>= 5 BU)
Authorization decisions should be revisited if previously denied based on inhibitor-related criteria

Policy applicationPolicy requires agents prescribed for routine prophylaxis to follow FDA‑labeled dosing and supports prior authorization for prophylactic use