Xenpozyme (olipudase alfa-rpcp) — HCPCS J0218

First-in-class FDA approval — ASMD has no class peer FDA verified May 2026

Xenpozyme (FDA-approved August 2022) is the only enzyme replacement therapy ever approved for acid sphingomyelinase deficiency.

Acid sphingomyelinase deficiency (ASMD) is the molecular defect underlying Niemann-Pick disease types B (chronic visceral) and A/B (intermediate). Until August 2022, ASMD had no disease-modifying therapy of any kind — clinical management was limited to supportive care: transfusion for cytopenia, partial or total splenectomy for hypersplenism, supplemental oxygen for restrictive lung disease, and lipid-lowering therapy for the dyslipidemia driven by sphingomyelin storage. Xenpozyme is the first and only FDA-approved treatment.

Lysosomal storage disorder (LSD) ERT landscape

Xenpozyme joins a small set of recombinant ERTs that each target one specific LSD enzyme deficiency. These products are not interchangeable — each has a unique HCPCS, NDC, and clinical indication.

Dosing & unit math FDA label verified Aug 2022 rev

From FDA prescribing information for Xenpozyme (olipudase alfa-rpcp).

Adult and pediatric ASMD (post-escalation maintenance)

• 3 mg/kg IV every 2 weeks — maintenance dose after Day 98 of dose escalation; 26 doses/year
• Use actual body weight; for patients with BMI >30, body-indexed mass per FDA label may apply — verify with prescriber
• Lifelong therapy

Initiation — mandatory 14-week dose escalation (Days 1–98)

• Day 1: 0.03 mg/kg (test/initial dose)
• Titrate every 2 weeks per FDA label schedule (see 14-week escalation protocol) until Day 98 maintenance dose of 3 mg/kg is reached
• Premedicate with antihistamines, antipyretics, and corticosteroids 30–60 minutes before each escalation infusion
• Hold or reduce dose for transaminase elevations, infusion reactions, or hypersensitivity per label criteria

Unit math — the 1 mg billing unit

1 J0218 billing unit = 1 mg of olipudase alfa-rpcp. Total mg administered equals the unit count entered on the claim. Vial mixing (4 mg + 20 mg) is required to minimize waste, but small partial-vial waste is virtually always present on weight-based dosing — report on a separate JW line.

Worked example — maintenance dose (70 kg patient, 3 mg/kg q2w)

Worked example — first escalation dose (70 kg patient, 0.03 mg/kg)

14-week dose escalation protocol FDA label verified May 2026

Mandatory titration from Day 1 (0.03 mg/kg) to Day 98 (3 mg/kg maintenance). Skipping or compressing the schedule is contraindicated.

The 14-week titration is engineered to limit the inflammatory burden of rapidly mobilizing accumulated sphingomyelin from liver, spleen, and lung. Cytokine release (IL-6, IL-8, TNF) and transaminase elevations are expected during titration and are mitigated by slow, stepwise dose increases plus premedication. Per FDA label, every patient — adult or pediatric, treatment-naive or restart after extended interruption — must complete the full escalation.

Restart after interruption

• Brief interruptions (1–2 missed doses): resume at the prior dose level per prescriber judgment
• Extended interruption (typically >28 days off therapy or per label criteria): full re-escalation may be required
• Document the interruption rationale and the resumption schedule for payer reauthorization

Premedication protocol FDA label verified May 2026

Recommended for every infusion during dose escalation; clinician judgment for maintenance.

Premedication is recommended 30–60 minutes prior to each Xenpozyme infusion during dose escalation to mitigate hypersensitivity, cytokine release, and infusion-associated reactions. The regimen is not a fixed combination; clinicians select agent classes appropriate to the patient and prior reaction history.

NDC reference FDA NDC Directory verified May 2026

Administration codes CPT verified May 2026

Xenpozyme is non-chemo enzyme replacement therapy — therapeutic IV codes only.

Modifiers CMS verified May 2026

JZ + JW — both apply on virtually every claim

Xenpozyme comes only in 4 mg and 20 mg single-dose vials, and dosing is weight-based. Even with optimal vial mixing, partial-vial waste is virtually always present at maintenance doses (e.g., 70 kg adult at 210 mg requires 212 mg drawn = 2 mg waste). Bill JW with the discarded mg on a separate claim line, AND JZ on the administered mg per CMS's July 2023 single-dose container policy.

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. Routine pre-infusion clinical assessment is bundled into the infusion service.

340B modifiers (JG, TB)

For 340B-acquired Xenpozyme, follow your MAC's current 340B modifier policy. Sanofi's billing guide does not provide 340B-specific instructions; defer to MAC LCD and your hospital's 340B compliance team.

ICD-10-CM diagnosis coding FY2026 verified May 2026

E75.24x family supports the ASMD claim; specific subtype use depends on confirmed diagnosis.

Site of care & place of service Verified May 2026

Site-of-care utilization management on rare-disease ERTs is generally less aggressive than on common biologics, but commercial payers still steer stable Xenpozyme patients out of HOPD into office, ambulatory infusion suite, or home infusion settings after the escalation phase.

Claim form field mapping Sanofi Patient Connection 2025

From Sanofi Xenpozyme reimbursement guide (Sanofi Patient Connection HCP materials).

Payer policy snapshot Reviewed May 2026

All major payers gate Xenpozyme behind diagnostic confirmation and specialist consultation. As the only ASMD treatment, formulary brand selection is not in play.

Step therapy

Step therapy is not applicable — there is no alternative ASMD therapy to step through. Some payers may require documentation of supportive care attempts (e.g., transfusion for cytopenia, lipid management for dyslipidemia) but these are not standard step requirements.

Reauthorization

Annual reauthorization is the norm. Submit current Hgb, platelet count, hepatic and splenic volumes (typically by MRI), pulmonary function (DLCO if relevant), lipid panel, and biomarker / disease-burden trend. Documented stability or improvement on therapy supports continued coverage. The 14-week escalation does not need to be repeated unless the patient has had an extended treatment interruption per FDA label criteria.

Medicare reimbursement CMS Q2 2026 (live)

Quarterly ASP from CMS Part B Drug Pricing File. Refreshes automatically each quarter.

Coverage

Xenpozyme is covered by all MACs under their generic Part B drug-coverage framework with appropriate E75.24x + diagnostic documentation. As of May 2026, no NCD specific to olipudase alfa-rpcp; local MAC LCDs may exist for rare-disease ERTs. Verify per jurisdiction.

Code history

• J0218 — permanent code, descriptor "Inj olipudase alfa-rpcp 1mg"; assigned after FDA approval (August 2022)

Patient assistance — Sanofi Patient Connection Sanofi verified May 2026

• Sanofi Patient Connection: 1-800-745-4447 — benefits investigation, prior authorization assistance, appeal support, copay program enrollment, free-drug program for eligible patients
• Xenpozyme Patient Support: dedicated case management for ASMD patients on Xenpozyme; coordinates infusion center logistics, escalation tracking, and ongoing support
• Commercial copay assistance: available for eligible commercially-insured patients (excludes Medicare, Medicaid, federal program patients)
• Patient assistance program (PAP): free product for uninsured / underinsured patients meeting income criteria
• Foundations (Medicare patients): National Niemann-Pick Disease Foundation, PAN Foundation (verify open lysosomal storage disease funds quarterly), HealthWell Foundation
• Web: sanofipatientconnection.com

Common denials & how to fix them

Frequently asked questions

What is the HCPCS code for Xenpozyme?

Xenpozyme (olipudase alfa-rpcp) is billed under HCPCS J0218 — "Inj olipudase alfa-rpcp 1mg." One billing unit equals 1 mg. A 3 mg/kg maintenance dose for a 70 kg patient = 210 mg = 210 units. J0218 is a permanent code added after FDA approval in August 2022.

How many units do I bill for a 3 mg/kg Xenpozyme maintenance dose?

Bill total mg administered as units (1 mg = 1 unit). A 70 kg adult at the 3 mg/kg maintenance dose receives 210 mg = 210 units of J0218 every 2 weeks. Vial mixing of 20 mg + 4 mg vials produces minor partial-vial waste (~2 mg = 2 units JW per dose). During the 14-week dose escalation phase, unit counts are much smaller — start at 0.03 mg/kg (~2 mg for a 70 kg adult) and titrate upward per protocol.

What administration CPT do I use for Xenpozyme?

96365 (initial therapeutic IV infusion, up to 1 hour) plus 96366 (each additional hour) — bill 2 units of 96366 for the typical ~3-hour escalation infusion. Olipudase alfa-rpcp is enzyme replacement therapy, not chemotherapy, so chemo administration codes (96413/96415) are NOT appropriate.

Do I bill JZ or JW for Xenpozyme?

Both apply on most claims. Xenpozyme comes only as 4 mg and 20 mg single-dose vials, and dosing is weight-based — virtually every dose produces partial-vial waste. Bill JW with the discarded mg on a separate claim line, AND JZ on the administered mg. Per CMS's July 2023 single-dose container policy, every J0218 claim must carry one of JZ or JW.

Is dose escalation mandatory for Xenpozyme?

Yes. Per the FDA label, Xenpozyme MUST be initiated at 0.03 mg/kg and titrated stepwise over 14 weeks (Days 1–98) before reaching the 3 mg/kg maintenance dose. The escalation mitigates infusion-associated reactions and cytokine release driven by rapid sphingomyelin breakdown. Skipping or compressing titration is contraindicated by the label and will be denied by payers. Premedication (antihistamines, antipyretics, corticosteroids 30–60 min pre-infusion) is recommended throughout the escalation phase.

What is the Medicare reimbursement for J0218?

For Q2 2026, the Medicare Part B payment limit for J0218 is $395.598 per mg (1 unit) under ASP + 6%. A 3 mg/kg maintenance dose for a 70 kg patient (210 mg = 210 units) reimburses at approximately $83,075.58 per infusion, or roughly $2,159,965/year on a q2w schedule (26 maintenance doses). Sequestration (~2%) reduces actual paid to roughly ASP + 4.3%.

What ICD-10 code is used for ASMD / Niemann-Pick disease?

E75.249 ("Niemann-Pick disease, unspecified") is the most commonly used ICD-10 code for ASMD on Xenpozyme claims, because the FDA-approved indication covers ASMD type B (chronic) and type A/B (intermediate) but ICD-10 lacks a unique acid sphingomyelinase deficiency code. Specific subtypes: E75.241 (type A — not approved for neurologic manifestations), E75.242 (type B — primary Xenpozyme target), E75.243 (type C1 — NOT an ASMD condition; do not use for Xenpozyme). Diagnosis must be confirmed by acid sphingomyelinase enzyme assay AND SMPD1 gene mutation analysis.

Is there an alternative to Xenpozyme for ASMD?

No. Xenpozyme (FDA-approved August 2022) is the first and only FDA-approved treatment for acid sphingomyelinase deficiency (ASMD), the disease underlying Niemann-Pick disease type B and type A/B. Prior to Xenpozyme, ASMD was managed exclusively with supportive care (transfusion for cytopenia, splenectomy for hypersplenism, oxygen for pulmonary disease, lipid-lowering therapy). Xenpozyme is NOT indicated for the neurologic manifestations of ASMD type A. Other LSD ERTs (Cerezyme, Fabrazyme, Aldurazyme) treat distinct enzyme deficiencies and are not interchangeable.

Does Xenpozyme have a Boxed Warning?

No. Xenpozyme has no Boxed Warning. Warnings & Precautions cover hypersensitivity reactions including anaphylaxis (premedicate during escalation), infusion-associated reactions and cytokine release (the rationale for the 14-week titration), elevated transaminases (monitor LFTs at baseline and periodically — temporary elevation is expected as substrate mobilizes from the liver), and embryo-fetal toxicity (effective contraception recommended).

Source documents

1. DailyMed — XENPOZYME (olipudase alfa-rpcp) Prescribing Information
   FDA-approved label (BLA, August 2022); current revision
2. Sanofi Patient Connection — Xenpozyme HCP reimbursement & coverage materials
   Patient enrollment, free-drug program, copay assistance, BI/PA support: 1-800-745-4447
3. CMS — Medicare Part B Drug ASP Pricing File
   Q2 2026 quarterly file, effective April 1 – June 30, 2026
4. SEER CanMED — HCPCS J0218 reference
   Permanent code descriptor: "Inj olipudase alfa-rpcp 1mg"
5. FDA Press Release — First treatment for ASMD (August 2022)
   First-in-class FDA approval announcement
6. UnitedHealthcare — Rare Disease ERT medical drug policy
7. Aetna CPB — Enzyme Replacement Therapy for Rare Diseases
8. National Niemann-Pick Disease Foundation — clinician resources
9. FDA National Drug Code Directory
10. GeneReviews — Acid Sphingomyelinase Deficiency (ASMD) natural history and management

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 2, 2026 — Initial publication. ASP data: Q2 2026 ($395.598/mg). Manufacturer source: Sanofi Patient Connection 2025. FDA label: August 2022 first-in-class approval, current revision. Includes 14-week dose escalation protocol, premedication checklist, and LSD ERT class context.

Methodology

Every claim on this page is sourced inline. Pricing reflects the current CMS Part B Drug ASP Pricing File. Payer policies are read directly from each payer's published medical/pharmacy policy documents. Diagnostic and dosing criteria reference the FDA label, ASMD natural history studies, and published clinical trial data for olipudase alfa. We do not paraphrase from billing-software vendor blogs.