Hemgenix (etranacogene dezaparvovec-drlb) — HCPCS J1411

Hemophilia B therapy class — J1411 (Hemgenix gene therapy) vs FIX replacement (IDELVION / IXINITY / Alprolix / Rebinyn / BeneFIX) CMS HCPCS verified May 2026

Two completely different treatment paradigms for hemophilia B. Don't confuse them at the claim layer.

Hemophilia B (congenital factor IX deficiency, also called Christmas disease) is treated by two paradigms: (1) FIX replacement therapy — standard-half-life or extended-half-life recombinant factor IX given on demand or as prophylaxis multiple times per month indefinitely (IDELVION, IXINITY, Alprolix, Rebinyn, BeneFIX, and plasma-derived FIX concentrates), and (2) Hemgenix gene therapy — one-time IV AAV5 vector delivering a FIX-Padua transgene to hepatocytes for sustained endogenous FIX production. They have entirely different mechanisms, schedules, and billing pathways.

Dosing & unit math FDA label verified May 2026

From the FDA-approved Hemgenix prescribing information (BLA 125772; label rev April 2026). Unit-of-billing is the per-therapeutic-dose event, not vials or vg; the underlying physical dose is weight-based vector genome copies.

Approved indication

• Hemophilia B (congenital factor IX deficiency) in adult patients (≥18 years) who:
  • currently use factor IX prophylaxis therapy, OR
  • have current or historical life-threatening hemorrhage, OR
  • have repeated, serious spontaneous bleeding episodes.
• Severity is typically severe (FIX activity ≤ 2 IU/dL) or moderate (FIX activity 2–5 IU/dL) hemophilia B; documentation must include the most recent FIX activity assay result.

Weight-based dosing

Worked example — 70 kg adult on routine HTC hemophilia B workflow

Dose modifications

Per FDA label, Hemgenix dosing is fixed at 2 × 10¹³ vg/kg. There is no dose reduction pathway because the therapy is one-time and the AAV5 vector is sized to deliver therapeutic FIX-Padua transgene copies to hepatocytes. If pre-infusion LFTs, hepatitis serology, or FIX inhibitor status are out of range, the infusion is held rather than dose-reduced; the patient continues FIX prophylaxis while eligibility is re-established.

Anti-AAV5 NAb pre-treatment gate

Before infusion, anti-AAV5 neutralizing antibody (NAb) titer should be measured. Important nuance: the current FDA label (April 2026 revision) does not establish a hard numerical exclusion cutoff. The label describes that patients with pre-existing anti-AAV5 NAb titers up to 1:678 in the HOPE-B pivotal trial showed mean Factor IX activity that was numerically lower than seronegative patients but still clinically meaningful, and a single patient with a very high titer (1:3212) did not respond adequately. Most payer policies and CSL Behring patient support workflow operationalize the HOPE-B 1:678 threshold as the practical eligibility cutoff because that is the upper limit of documented response in the pivotal trial. Testing is coordinated through CSL Behring patient support and is a critical element of the workflow. Approximately 21% of adult hemophilia B patients screened in HOPE-B had detectable anti-AAV5 antibodies. Note: pre-existing AAV5 seropositivity is more common than AAV9 seropositivity in adults because AAV5 is a common environmental wild-type virus. Document the titer, the assay used, and the clinical decision rationale in the PA packet.

NDC reference FDA NDC Directory verified May 2026

Administration codes CPT verified May 2026

Hemgenix is a therapeutic IV infusion (not chemo, not radiopharm, not a factor replacement push). Use therapeutic IV admin codes.

Modifiers CMS verified May 2026

JZ / JW — generally N/A for single-dose patient-specific gene therapy

Hemgenix kits are patient-specific, lot-traceable, and built to deliver the exact weight-based dose. There is no physical "vial waste" in the conventional J-code sense — the entire shipped product is intended for administration to that named patient. JZ may be reported on J1411 to attest "no discarded amount from a single-dose container," consistent with CMS's July 2023 single-dose container policy, but practice varies by MAC and the per-therapeutic-dose unit definition makes JZ/JW reporting largely moot. Confirm with your MAC.

Modifier 25 — same-day E/M

Use modifier 25 on the E/M code when a significant, separately identifiable evaluation and management service is performed on the same day as the infusion (consent, extended hematology counseling, baseline bleed assessment, review of weekly LFT monitoring plan, FIX prophylaxis bridging discussion).

340B modifiers (JG, TB)

Most Hemgenix is dispensed under the specialty product / specialty distribution pathway rather than via 340B, but a small number of HTC-affiliated 340B-covered entities may administer 340B-acquired Hemgenix. Confirm with your 340B compliance team and your MAC's modifier guidance. Outcomes-based contracts can complicate 340B reporting because the manufacturer rebate flow interacts with 340B pricing assumptions.

Contract-specific modifiers

Some commercial payers add a contract-specific modifier or claim attachment requirement to flag claims under an outcomes-based agreement (so the claim can be linked to the manufacturer's milestone-tracking dataset). Follow the payer's outcomes-based contract operational guide; CSL Behring patient support coordinates this end-to-end.

ICD-10-CM by indication FY2026 verified May 2026

Hemgenix is indicated for adults with hemophilia B (congenital FIX deficiency). Use D67 plus supporting codes documenting bleeding history and prior FIX prophylaxis.

Site of care & place of service Verified May 2026

Hemgenix is administered exclusively in certified hemophilia treatment centers (HTCs) — almost always a federally-funded HTC (one of ~140 in the US National HTC Network) with a multi-disciplinary hemophilia / bleeding-disorders program. The administration is typically performed in a hospital inpatient unit (planned short admission) or in a hospital outpatient infusion suite under extended observation. Office-based (POS 11), ambulatory infusion center (POS 49), and home infusion administration is not appropriate given the high-cost product, infusion-reaction risk, and post-infusion hepatic monitoring requirements.

Claim form field mapping CSL Behring 2026

Hemgenix claims are typically submitted on UB-04 (837I) by the certified HTC.

Payer policy snapshot Reviewed May 2026

Universal PA. Anti-AAV5 NAb < 1:678, hemophilia B (D67) with FIX activity assay, age ≥18, documented prior FIX prophylaxis history OR life-threatening/repeated bleeding episodes, hepatitis B/C/HIV serology, FIX inhibitor negative, and HTC certification are the universal documentation requirements.

Outcomes-based contracts — how they work for billers

CSL Behring offers outcomes-based agreements (OBAs) with most major commercial payers and a growing list of state Medicaid programs. The typical structure: full WAC (~$3.5M) is paid at administration; if specified clinical milestones are not met over a 5-year horizon, a percentage of the WAC is refunded by the manufacturer to the payer. Milestones commonly include sustained FIX activity threshold (e.g., > 5 IU/dL or > 12 IU/dL at multiple timepoints), annualized bleed rate (ABR) reduction, and elimination or reduction of FIX product utilization. The provider's role: document FIX activity (chromogenic and one-stage assays), bleed events, and FIX product use at standardized intervals (3, 6, 12, 24, 36, 60 months post-infusion). CSL Behring patient support coordinates this longitudinally. The rebate/refund flow is payer-side and does not affect the provider's payment at administration.

CMS Cell and Gene Therapy (CGT) Access Model

In January 2025, CMS launched the Cell and Gene Therapy Access Model, a voluntary multi-state Medicaid arrangement designed specifically for high-cost one-time gene therapies starting with sickle cell disease and expanding to hemophilia. CSL Behring and participating states negotiate uniform outcomes-based pricing through CMS as a facilitator. Verify your state's participation status and the impact on Hemgenix Medicaid PA / claim workflow with your state Medicaid agency.

Step therapy & prior FIX therapy

Hemgenix's FDA label explicitly requires documentation of current FIX prophylaxis OR life-threatening hemorrhage OR repeated serious spontaneous bleeding episodes. In practice, this means nearly every Hemgenix candidate has been on prophylactic FIX (IDELVION, Alprolix, BeneFIX, Rebinyn, or IXINITY) before gene therapy. Document the FIX product history (manufacturer, dose, schedule, duration, ABR on FIX prophylaxis) in the PA packet as direct evidence the label criterion is met.

Medicare / Medicaid reimbursement CMS Q2 2026 (NOC / invoice)

Hemgenix is not currently priced via the standard quarterly ASP file (NOC / invoice pathway). For inpatient HOPD administration, J1411 may be packaged into the DRG with NTAP or outlier payment; for outpatient, OPPS pass-through historically applied.

Inpatient (Medicare / Medicaid)

When Hemgenix is administered inpatient, the drug cost is bundled into the assigned DRG. Without a high-cost outlier or New Technology Add-On Payment (NTAP), this is not financially viable for the hospital. Most state Medicaid programs and Medicare contractors have negotiated supplemental rebate agreements (SRAs) and outcomes-based agreements specifically to handle Hemgenix cash flow. The CMS Cell and Gene Therapy (CGT) Access Model provides a multi-state Medicaid framework. Confirm the state Medicaid or Medicare contractor policy and the hospital's contract before scheduling the inpatient admission.

Outpatient (Medicare / Medicaid)

For outpatient HOPD administration, J1411 is billed with the appropriate revenue code (0636 or 0260 per payer), CPT 96365 admin, and supporting documentation. OPPS pass-through (if active) pays the drug at ASP+6% / invoice; if pass-through has expired, packaging into the APC bundle is generally not viable and outpatient billing depends on payer-specific contractor pricing.

Coverage

No NCD specific to Hemgenix or to AAV-based gene therapies generally. Coverage falls under MAC LCDs and payer-specific medical / pharmacy benefit policies. All MACs and major commercial payers cover J1411 for FDA-approved on-label indications with documented hemophilia B (D67), age ≥ 18, anti-AAV5 NAb < 1:678, FIX inhibitor negative, hepatitis B/C/HIV serology, and the required pre-/post-infusion monitoring framework.

Code history

• J1411 — "Injection, etranacogene dezaparvovec-drlb, per therapeutic dose"; effective dates vary by CMS HCPCS quarterly file (introduced after the November 2022 FDA approval). Verify the current descriptor and effective date.
• C9399 — transitional pass-through C-code historically used at initial launch (2022–2023); retired when J1411 became permanent.
• J3490 — unclassified drug code; historically used at launch for some payers; not appropriate once J1411 is permanent.
• J3590 — unclassified biologic code; legacy alternative to J3490 for biologics; not appropriate once J1411 is permanent.

Patient assistance — CSL Behring patient support CSL Behring verified May 2026

• CSL Behring Hemgenix patient support: CSL Behring main line 1-800-676-4266 — benefits investigation, prior authorization assistance, anti-AAV5 NAb testing logistics, certified HTC referral, travel and lodging support, FIX prophylaxis bridging coordination, post-infusion monitoring scheduling, outcomes-based contract operational support
• CSL Behring Patient Assistance Foundation: 501(c)(3) charitable foundation providing free product for uninsured / underinsured patients meeting income requirements; Hemgenix access pathway is highly individualized given the WAC scale
• National Bleeding Disorders Foundation (NBDF, formerly NHF): bleeding.org — federally-funded HTC directory, MASAC clinical guidelines (Medical and Scientific Advisory Council) including the MASAC document on gene therapy in hemophilia, peer/patient support, emergency financial assistance for travel and lodging
• Hemophilia Federation of America (HFA): hemophiliafed.org — patient advocacy, financial assistance programs, helping hands grants for emergency needs, mentorship and educational resources for adults considering gene therapy
• Foundations: PAN Foundation (rare/genetic disease funds where applicable), HealthWell Foundation, Patient Advocate Foundation — primarily supplemental for non-drug costs (travel, lodging, monitoring labs); verify open hemophilia / rare-disease funds quarterly
• Travel & lodging: CSL Behring patient support coordinates with Healthcare Hospitality Network, Ronald McDonald House (rare for adult patients), and Hope Lodge for patients traveling to certified Hemgenix HTCs (regional access varies)

Safety & FDA-label monitoring FDA label warnings & precautions

FDA-label warnings & precautions

• Hepatotoxicity / transaminase elevations: ALT elevations occur in approximately 17% of patients in the HOPE-B trial. Monitor ALT, AST, alkaline phosphatase, and total bilirubin at baseline (within 2 weeks pre-infusion) and weekly for at least 3 months post-infusion. If ALT rises > 2× baseline or above ULN, initiate reactive oral corticosteroid taper (commonly prednisone 60 mg/day with gradual taper over 8–12 weeks); coordinate with HTC hepatology consult.
• Infusion reactions: can occur during or immediately after the infusion. Monitor vital signs during and for at least 3 hours post-infusion in HTC setting; have emergency response capability on standby. Pre-medication is not routinely required but may be considered per HTC protocol.
• Immune-mediated response / immunogenicity: patients seroconvert (develop anti-AAV5 antibodies) after Hemgenix; re-dosing is not feasible. The label warns of immune-mediated response that can reduce FIX expression.
• Theoretical risk of malignancy (AAV vector integration): the long-term safety monitoring plan includes annual or biannual follow-up for hepatic adverse events including hepatocellular carcinoma for up to 15 years; coordinate with HTC long-term registry.
• Active hepatitis B / C / HIV: patients with detectable hepatitis B or C viral load or uncontrolled HIV are excluded; the AAV5 vector is hepatotropic and uncontrolled hepatic infection increases risk. Document negative serology pre-infusion.
• Anti-AAV5 NAb seropositivity: patients with anti-AAV5 NAb titer ≥ 1:678 are excluded per HOPE-B; lower titers may reduce vector transduction but are not absolutely excluded — document shared decision-making.
• Embryo-fetal toxicity: Hemgenix is not indicated in pregnant patients; reproductive counseling for adults of reproductive age.

Outcomes-based milestone tracking

Beyond the FDA-label safety monitoring, the manufacturer's outcomes-based contract typically requires documentation of FIX activity (chromogenic and one-stage assays), annualized bleed rate (ABR), and FIX product utilization at 3, 6, 12, 24, 36, and 60 months post-infusion. CSL Behring patient support coordinates this longitudinal data collection in cooperation with the certified HTC. Long-term safety registries (up to 15 years) capture malignancy and durability data per FDA post-marketing commitments.

Common denials & how to fix them

Frequently asked questions

Is Hemgenix a one-time treatment?

Yes. Hemgenix is administered as a single one-time IV infusion. There is no repeat or maintenance dose. The FIX-Padua transgene delivered by the AAV5 vector is intended to drive endogenous factor IX production in hepatocytes for years post-infusion (the HOPE-B trial demonstrated durable FIX activity at multiple years of follow-up). Re-dosing is not supported by the label and is generally not feasible because patients seroconvert (develop high-titer anti-AAV5 antibodies) after the first administration.

What is the HCPCS code for Hemgenix?

Hemgenix is billed under HCPCS J1411 — "Injection, etranacogene dezaparvovec-drlb, per therapeutic dose." This is a single-dose, per-therapeutic-dose J-code (not per-mg or per-vector-genome). Each Hemgenix administration is billed as J1411 × 1 unit. Do not use J3490 / J3590 unclassified or C9399 transitional pass-through (all retired/legacy).

Why is Hemgenix the world's most expensive drug?

At ~$3.5M list price, Hemgenix has held the title of world's most expensive drug since its November 2022 launch, surpassing Zolgensma's ~$2.125M. The pricing reflects: (1) one-time replacement of years of FIX prophylaxis spend ($300K–$900K/year for severe hemophilia B), (2) very small eligible patient population (hemophilia B prevalence ~1 in 25,000 male births; only a fraction are AAV5-NAb-eligible adults), (3) complex manufacturing and patient-specific kit-build, and (4) the outcomes-based contracting framework that defers payment risk to the manufacturer if FIX activity / ABR milestones are not met.

What is the anti-AAV5 NAb threshold?

Per the HOPE-B pivotal trial exclusion criteria, patients with anti-AAV5 neutralizing antibody (NAb) titer ≥ 1:678 were excluded. The FDA label reflects this gate. Approximately 21% of hemophilia B patients screened had detectable anti-AAV5 antibodies. Missing or absent NAb documentation is the #1 cause of Hemgenix PA denial. Coordinate testing through CSL Behring patient support 4 weeks ahead of the planned infusion.

How does outcomes-based contracting work for Hemgenix billers?

CSL Behring offers outcomes-based agreements (OBAs) to payers. Full WAC is paid at administration; if specified clinical milestones (sustained FIX activity, ABR reduction, FIX product use reduction) are not met over a 5-year horizon, a percentage of WAC is refunded by the manufacturer to the payer. The provider organization is not party to the rebate flow but documents FIX activity (chromogenic and one-stage), bleeding events, and FIX product use at 3, 6, 12, 24, 36, and 60 months post-infusion. CSL Behring patient support coordinates this longitudinal data collection.

How is Hemgenix administration paid for given the $3.5M price tag?

Through payer contracts and outcomes-based agreements, not patient out-of-pocket. Most adult patients are commercial-payer or Medicare-eligible; severe hemophilia B patients often qualify for Medicare under disability. State Medicaid programs increasingly access Hemgenix through the CMS Cell and Gene Therapy Access Model (multi-state Medicaid framework launched 2025). Commercial payers use a combination of standard medical benefit + stop-loss reinsurance + outcomes-based contracts + benefit-pool carve-outs. Patient OOP exposure is typically capped at the plan's OOP maximum (varies by plan), not the WAC. CSL Behring patient support and copay-assistance foundations help bridge any residual exposure.

Inpatient billing vs outpatient billing — which is right?

Both pathways are used. Many HTCs bill inpatient under a planned short admission (DRG with NTAP / outlier payment). Other HTCs bill outpatient with extended observation under OPPS pass-through (if active for the calendar year). The choice is driven by payer contract, hospital revenue cycle policy, and clinical risk tolerance. Confirm with the hospital's revenue cycle team and the payer before scheduling.

Is corticosteroid prophylaxis required?

Reactive, not routine prophylactic. Unlike Zolgensma (mandatory pre-infusion oral prednisolone for SMA), the Hemgenix label does not require routine prophylactic corticosteroids. However, transaminase elevations (~17% in HOPE-B) typically trigger a reactive 8–12-week tapering oral prednisone course (commonly 60 mg/day) when ALT rises > 2× baseline or > ULN. Document the reactive plan in the PA packet and chart at every weekly monitoring visit.

What liver toxicity monitoring is required?

Per FDA label: ALT, AST, alkaline phosphatase, and total bilirubin at baseline (within 2 weeks pre-infusion) and weekly for at least 3 months post-infusion. Concurrent FIX activity assay at protocol-defined timepoints (typically week 3 and per HTC protocol thereafter). Document the monitoring schedule in the PA packet and chart at every visit. Hepatitis B / C / HIV serology must be negative pre-infusion.

How do the National Bleeding Disorders Foundation and HFA support patients?

The National Bleeding Disorders Foundation (NBDF, bleeding.org; formerly NHF) and Hemophilia Federation of America (HFA, hemophiliafed.org) do not directly pay for Hemgenix drug cost (that is the payer / Medicare / Medicaid / CSL Behring path). They provide: federally-funded HTC directory, MASAC clinical guidelines (NBDF), helping hands financial assistance (HFA), peer/patient support, and emergency travel/lodging assistance. Refer adults considering gene therapy to NBDF and HFA early in the PA process.

Can a patient on IDELVION switch to Hemgenix?

Yes — Hemgenix's label explicitly covers patients on FIX prophylaxis. Switching is gated by anti-AAV5 NAb < 1:678, age ≥ 18, hemophilia B severity, hepatic and serology clearance, and FIX inhibitor negative. After Hemgenix, the FIX prophylaxis is typically discontinued once endogenous FIX activity reaches a sustainable threshold (commonly > 5 IU/dL); some HTCs continue FIX prophylaxis as a safety bridge for 1–3 months. Document the bridging plan in the PA packet.

Hemgenix vs Hemlibra vs Alhemo — which is which?

Three different non-FIX-replacement bleeding-disorder therapies with very different roles. Hemgenix (this page, J1411) is one-time AAV5 gene therapy for adult hemophilia B (FIX deficiency). Hemlibra (J7170) is a bispecific FVIIIa mimetic for hemophilia A prophylaxis (factor VIII deficiency), given subcutaneously weekly to monthly indefinitely. Alhemo (J7173) is an anti-TFPI mAb for prophylaxis in hemophilia A or B with inhibitors. They are not interchangeable — different mechanisms, different patient populations, different J-codes, completely different schedules.

Source documents

1. DailyMed — HEMGENIX (etranacogene dezaparvovec-drlb) current FDA label
   Current FDA-approved label (BLA 125772, rev April 2026; SETID 35b2db65-4c6c-4173-ab56-b2bca69193bd) including warnings & precautions for hepatotoxicity, infusion reactions, immune-mediated response, theoretical malignancy risk, dosing, AAV5 NAb data, monitoring schedule, NDC, package insert
2. FDA Drugs@FDA — HEMGENIX (BLA 125772)
   FDA approval history, supplements, and current prescribing information for etranacogene dezaparvovec-drlb (originally approved November 22, 2022)
3. CSL Behring — Hemgenix product page
   Manufacturer hub: benefits investigation, PA assistance, anti-AAV5 NAb testing logistics, certified HTC directory, outcomes-based contract operations
4. CMS — Medicare Part B Drug ASP Pricing File
   Quarterly ASP file; J1411 historically priced via NOC / invoice rather than via ASP file (verify quarterly)
5. CMS — OPPS Addendum A / Addendum B
   Hospital outpatient status indicators; check J1411 status quarterly (pass-through vs packaged)
6. CMS — Cell and Gene Therapy (CGT) Access Model
   Multi-state Medicaid framework for high-cost gene therapies; launched January 2025, includes hemophilia
7. National Bleeding Disorders Foundation (NBDF, formerly NHF)
   Federally-funded HTC directory, MASAC clinical guidelines (including MASAC document on gene therapy in hemophilia), peer/patient support
8. Hemophilia Federation of America (HFA)
   Patient advocacy, helping hands grants for emergency needs, mentorship for adults considering gene therapy
9. Pipe et al., NEJM 2023 — HOPE-B pivotal trial of etranacogene dezaparvovec
   Phase 3 single-arm trial; basis for FDA approval; anti-AAV5 NAb gate < 1:678 established here
10. UnitedHealthcare — Hemgenix Medical Drug Policy
11. Aetna CPB — Etranacogene Dezaparvovec
12. FDA National Drug Code Directory
13. CMS — JW/JZ modifier policy (CR 12056, eff. July 2023)

About this page

We maintain this page as a living reference. Medicare ASP pricing is bound to our underlying CareCost data layer and refreshes automatically when CMS publishes new quarterly files. Coding and policy content is reviewed at least quarterly and updated whenever a source document changes.

Found an error? Email hello@carecostestimate.com.

Refresh cadence

Reviewer

Change log

• May 22, 2026 — SME audit pass: BLA corrected (125740 → 125772), label revision date verified (April 2026), DailyMed SETID added to source list, AAV5 NAb pre-treatment gate language clarified to distinguish FDA label content from HOPE-B operational threshold. No new boxed warnings; warnings & precautions unchanged.
• May 22, 2026 — Initial publication. ASP data: Q2 2026 (J1411 priced via NOC / invoice; not in standard ASP layer). Second gene therapy page in the CareCost catalog (after Zolgensma). Manufacturer source: CSL Behring 2026. Comparison vs FIX replacement (IDELVION, IXINITY, Alprolix, Rebinyn, BeneFIX) and adjacent non-factor therapies (Hemlibra, Alhemo). HOPE-B pivotal trial data referenced for anti-AAV5 NAb gate (< 1:678) and transaminase elevation frequency (~17%).

Methodology

Every claim on this page is sourced inline. Pricing reflects the current CMS Part B Drug ASP Pricing File and the OPPS Addendum B status indicator (where applicable; J1411 is commonly priced via NOC / invoice). Payer policies are read directly from each payer's published medical/pharmacy policy documents. Indication list, dosing, anti-AAV5 NAb threshold, corticosteroid plan, and monitoring schedule are verified against the current FDA label revision. Outcomes-based contracting context is verified against CSL Behring patient support operational guidance and the CMS Cell and Gene Therapy Access Model framework. We do not paraphrase from billing-software vendor blogs.