HCPCS
J1458
1 mg = 1 unit
Phase 1
Identify what you're billing
Confirm the MPS subtype, the right ERT, and the right HCPCS before billing.
About Naglazyme & MPS VI FDA verified May 2026
Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome) is an ultra-rare lysosomal storage disorder. Naglazyme is the only FDA-approved enzyme replacement for it.
Naglazyme (galsulfase) is a recombinant form of human N-acetylgalactosamine-4-sulfatase (also called arylsulfatase B / ARSB), produced in Chinese hamster ovary (CHO) cell culture. It supplies the missing or deficient enzyme in patients with MPS VI, slowing the progressive accumulation of dermatan sulfate and chondroitin-4-sulfate that drives MPS VI's multisystem manifestations: short stature, skeletal dysplasia, joint stiffness, cardiac valve disease, corneal clouding, hepatosplenomegaly, and respiratory compromise.
FDA approval was granted May 31, 2005 (BLA 125117) under accelerated approval, with full approval following confirmatory data. It is approved for patients ages 5 and older. MPS VI is ultra-rare — estimated prevalence approximately 1 in 250,000 to 1 in 600,000 live births in the US. Most patients are diagnosed in early childhood, though attenuated phenotypes can present in adulthood. Naglazyme is one of five MPS-specific enzyme replacement therapies on the US market (one for each of MPS I, II, IVA, VI, and VII).
Lifelong therapy. Naglazyme is not curative. It is given weekly for life. Discontinuation
leads to re-accumulation of glycosaminoglycans and clinical deterioration. PA renewals are routine but
require evidence of clinical benefit (urinary GAG reduction, 6-minute walk distance, joint range of
motion, cardiopulmonary status).
MPS treatment landscape FDA verified May 2026
Each mucopolysaccharidosis subtype has its own enzyme replacement therapy with a distinct HCPCS code. The wrong ERT for the wrong subtype is a frequent source of denials and adverse events.
| MPS subtype | Eponym | Drug (generic) | HCPCS | Enzyme replaced | Dosing |
|---|---|---|---|---|---|
| MPS I | Hurler / Hurler-Scheie / Scheie | Aldurazyme (laronidase) | J1931 |
Recombinant alpha-L-iduronidase | 0.58 mg/kg IV weekly |
| MPS II | Hunter | Elaprase (idursulfase) | J1743 |
Recombinant iduronate-2-sulfatase | 0.5 mg/kg IV weekly |
| MPS IVA | Morquio A | Vimizim (elosulfase alfa) | J1322 |
Recombinant N-acetylgalactosamine-6-sulfatase | 2 mg/kg IV weekly |
| MPS VI | Maroteaux-Lamy | Naglazyme (galsulfase) | J1458 |
Recombinant N-acetylgalactosamine-4-sulfatase (ARSB) | 1 mg/kg IV weekly |
| MPS VII | Sly | Mepsevii (vestronidase alfa-vjbk) | J3397 |
Recombinant beta-glucuronidase | 4 mg/kg IV every 2 weeks |
| MPS III (A-D) | Sanfilippo | No FDA-approved ERT — investigational only | |||
| MPS IVB | Morquio B | No FDA-approved ERT | |||
Confirm the subtype before submitting PA. All major payers require enzyme assay
confirmation (low ARSB activity in leukocytes or fibroblasts) plus ARSB gene mutation
analysis (biallelic pathogenic variants) for MPS VI diagnosis before approving Naglazyme. Diagnostic
confusion between MPS VI and other MPS subtypes is well documented — visual phenotype overlap is
substantial. The wrong ERT will not work biochemically and will be denied on appeal.
Dosing & unit math FDA label May 2026
From FDA prescribing information (BLA 125117).
Standard dosing
- 1 mg/kg actual body weight IV once weekly — lifelong therapy
- No loading dose. No interval extension. Same dose throughout childhood, adolescence, and adult life.
- Approved for patients ages 5 years and older
- 1 mg = 1 unit — bill the actual mg administered
- Vial: 5 mg / 5 mL (1 mg/mL) single-dose only — partial-vial waste is the norm
Infusion administration per FDA label
- Dilute calculated dose in 0.9% NaCl to a total volume per body weight (per label table)
- Initial infusion rate: slow titration over the first hour
- Remaining 3 hours at maximum tolerated rate
- Total infusion duration: ~4 hours
- Post-infusion observation period for delayed reactions
- No 0.2 micron in-line filter — do not filter (filter binding will reduce delivered dose)
Worked example — 70 kg adult, weekly Naglazyme infusion
# Calculate dose
Patient weight: 70 kg
Dose: 70 kg × 1 mg/kg = 70 mg
Vials needed: 70 mg ÷ 5 mg/vial = 14 vials
Drug units billed: 70 (J1458)
Modifier: JZ (no waste — weight is exact multiple of 5)
Admin: 96365 × 1 + 96366 × 3 (4-hour infusion)
# Year-1 totals (52 weekly doses)
Total drug units billed: 3,640 (52 × 70)
Total drug cost (Q2 2026 ASP+6%): ~$1,869,486 before sequestration
Patient weight: 70 kg
Dose: 70 kg × 1 mg/kg = 70 mg
Vials needed: 70 mg ÷ 5 mg/vial = 14 vials
Drug units billed: 70 (J1458)
Modifier: JZ (no waste — weight is exact multiple of 5)
Admin: 96365 × 1 + 96366 × 3 (4-hour infusion)
# Year-1 totals (52 weekly doses)
Total drug units billed: 3,640 (52 × 70)
Total drug cost (Q2 2026 ASP+6%): ~$1,869,486 before sequestration
Worked example — 73 kg adult (partial-vial waste)
# Calculate dose
Patient weight: 73 kg
Dose: 73 kg × 1 mg/kg = 73 mg
Vials needed: 73 mg ÷ 5 mg/vial = 14.6 → round up to 15 vials (75 mg drawn)
Administered: 73 mg · Discarded: 2 mg
Drug units billed (administered): 73 units with modifier JZ — NO, see below
# Correct billing per CMS JW/JZ rules
Line 1: J1458 × 73 units (administered) — no waste modifier
Line 2: J1458 × 2 units with modifier JW (discarded)
Total billed: 75 units · Total cost: ~$38,520
Patient weight: 73 kg
Dose: 73 kg × 1 mg/kg = 73 mg
Vials needed: 73 mg ÷ 5 mg/vial = 14.6 → round up to 15 vials (75 mg drawn)
Administered: 73 mg · Discarded: 2 mg
Drug units billed (administered): 73 units with modifier JZ — NO, see below
# Correct billing per CMS JW/JZ rules
Line 1: J1458 × 73 units (administered) — no waste modifier
Line 2: J1458 × 2 units with modifier JW (discarded)
Total billed: 75 units · Total cost: ~$38,520
Pediatric weight-based scenarios
- 15 kg child: 15 mg dose = 3 vials (no waste) → bill 15 units with JZ
- 22 kg child: 22 mg dose = 5 vials (3 mg waste) → bill 22 units (drug line) + 3 units JW (waste line)
- 40 kg adolescent: 40 mg dose = 8 vials (no waste) → bill 40 units with JZ
Premedication required (separate billing)
Per BOXED WARNING, premedicate every infusion with antihistamine + antipyretic 30-60 min before Naglazyme. See full premedication protocol. Bill diphenhydramine (J1200, 50 mg) on a separate claim line; acetaminophen typically self-administered or bundled.
NDC reference FDA NDC Directory verified May 2026
| NDC (10/11-digit) | Package | Use |
|---|---|---|
68135-0020-01 / 68135-020-01 |
5 mg / 5 mL (1 mg/mL) single-dose vial — 1 vial per carton | All Naglazyme dosing — only available vial size |
Only one NDC, one vial size. Naglazyme is supplied exclusively as 5 mg / 5 mL single-dose
vials. There is no multi-strength catalog. Weight-based dosing nearly always produces partial-vial waste
unless the patient's weight is a clean multiple of 5 kg. Bill JW for any discarded portion.
Storage: Refrigerate vials at 2-8°C (36-46°F). Do not freeze or shake. Diluted
infusion solution should be used immediately; if not, may be refrigerated for up to 24 hours and infused
within 24 hours. Discard unused diluted solution beyond this window.
Phase 2
Safety — anaphylaxis is the dominant clinical risk
Boxed warning. Premedicate every infusion. Resuscitation equipment required.
BOXED WARNING — Anaphylaxis FDA label verified May 2026
BOXED WARNING. Life-threatening anaphylactic reactions, including shock, respiratory
distress, angioedema, throat tightness, hypoxia, hypotension, urticaria, bradycardia, and bronchospasm,
have occurred during and within 24 hours after Naglazyme infusions. Naglazyme should be administered
in an appropriately equipped facility where cardiopulmonary resuscitation equipment is readily
available, by personnel trained to respond to medical emergencies. Patients with febrile or
respiratory illness at the time of Naglazyme infusion should be evaluated and treatment may need to
be delayed.
Documented reaction features
- Onset: typically during the infusion or within 24 hours after
- Manifestations: anaphylactic shock, respiratory distress, angioedema (face, lips, tongue, throat), throat tightness, hypoxia, hypotension, bradycardia, urticaria, bronchospasm, stridor
- Frequency: approximately half of treated patients experience some form of infusion-associated reaction; severe reactions in a smaller subset
- Risk factor: prior reactions, asthma, infusion rate (faster = higher risk), antibody development
Required clinical environment
- Healthcare professional administration only (NOT patient-administered, NOT home infusion without prior tolerance)
- Resuscitation equipment immediately available (epinephrine, IV fluids, oxygen, airway management)
- Personnel trained to respond to anaphylaxis
- Continuous patient monitoring during infusion + observation period after
Management of reactions
- Slow or pause infusion at first sign of reaction
- Treat with antihistamine, epinephrine, oxygen, IV fluids per anaphylaxis protocol
- Resume at lower rate after symptoms resolve, with additional premedication
- Severe or recurrent reactions: discontinue and consider alternative management
Sleep apnea, airway compromise, and Naglazyme. MPS VI patients frequently have airway
narrowing, sleep apnea, and cervical spine instability. Anaphylaxis in this population is more dangerous
than in the general population. Many specialist centers require respiratory therapy on standby and
anesthesia consultation for first infusions.
Premedication protocol FDA label verified May 2026
Required before EVERY Naglazyme infusion to reduce anaphylaxis and infusion reaction risk.
Premedication is REQUIRED, not optional. The FDA label specifies premedication 30-60
minutes before each Naglazyme infusion. Skipping premedication is a documented risk factor for severe
infusion reactions. Bill premedications separately under their own J-codes.
Standard premedication regimen
| Medication | Dose | Timing | Billing |
|---|---|---|---|
| Antihistamine (e.g., diphenhydramine) | 1 mg/kg PO/IV (max 50 mg) | 30-60 min pre-infusion | J1200 (diphenhydramine HCl, 50 mg) for IV; PO bundled |
| Antipyretic (acetaminophen) | 15 mg/kg PO (max 1 g) | 30-60 min pre-infusion | Typically self-administered or bundled; J0131 (acetaminophen IV) if IV given |
| Corticosteroid (e.g., methylprednisolone) | Per institutional protocol; commonly 1 mg/kg IV | 30-60 min pre-infusion | J2920 (methylprednisolone sodium succ, up to 40 mg) or J2930 (up to 125 mg) per dose |
When to escalate premedication
- Add corticosteroid for patients with prior infusion reactions, asthma history, or atopic disease
- Slow initial infusion rate further on subsequent infusion if mild reaction occurred
- Specialist re-consultation for any anaphylactic-grade reaction
Administration tracking
Document premedication administration in the infusion record: drug, dose, route, time, and patient response. CMS audits and payer reviews may request this documentation in conjunction with high-cost drug claims.
Phase 3
Code the claim
Therapeutic IV (NOT chemo). Long infusion = multiple additional-hour units. Document waste.
Administration codes CPT verified May 2026
Naglazyme is billed under therapeutic IV infusion codes (NOT chemotherapy codes). The 4-hour infusion produces multiple additional-hour billable units.
| Code | Description | When to use |
|---|---|---|
96365 |
Intravenous infusion, for therapy, prophylaxis, or diagnosis; initial, up to 1 hour | Primary code for Naglazyme. Bill once per infusion encounter. Covers first hour. |
96366 |
Intravenous infusion, for therapy, prophylaxis, or diagnosis; each additional hour (list separately) | Bill 3 units for the standard 4-hour Naglazyme infusion (hours 2, 3, 4). Round per CPT add-on rules. |
96367 |
IV infusion, additional sequential infusion of a new drug/substance, up to 1 hour | For sequential infusion of premedications via the same IV access (e.g., diphenhydramine before Naglazyme starts) |
96375 |
Therapeutic, prophylactic, or diagnostic injection; each additional sequential IV push of a new substance/drug | For IV push premedications (diphenhydramine push if not infused) |
96413 / 96415 |
Chemotherapy administration, IV infusion (initial / each additional hour) | NOT appropriate. Naglazyme is enzyme replacement, not chemotherapy. Use 96365/96366. |
Standard 4-hour infusion claim line:
96365 × 1 unit (initial hour)
+ 96366 × 3 units (hours 2, 3, 4). Plus one or more premedication admin codes
(96367 sequential or 96375 IV push) depending on how premedications are delivered.
Do not use 96413 chemo codes. Galsulfase is enzyme replacement therapy (not anti-neoplastic).
Chemo codes will trigger denials and audit attention. Therapeutic IV codes (96365/96366) are correct.
Modifiers CMS verified May 2026
JZ — when no waste occurs
Effective July 1, 2023, CMS requires the JZ modifier on all single-dose container claims when no drug is discarded. For Naglazyme, JZ applies when the patient's weight produces a dose that is an exact multiple of 5 mg (e.g., 35 kg = 35 mg = 7 vials, no waste; 70 kg = 70 mg = 14 vials, no waste).
JW — for partial-vial waste (most claims)
Naglazyme is supplied only in 5 mg single-dose vials. Any patient whose weight is not a multiple of 5
will produce partial-vial waste. Bill the discarded amount on a separate claim line with the
JW modifier. Example: a 73 kg patient receiving 73 mg uses 15 vials (75 mg drawn) —
bill JW with 2 units of waste alongside the 73-unit administered line. One of JZ or JW must
be on every J1458 claim.
Document the math on every claim. Naglazyme's high per-unit cost means every wasted
unit carries meaningful dollars. Payers will audit waste lines on high-cost biologics. Document patient
weight, calculated dose, vials drawn, mg administered, mg discarded, and waste justification (single-dose
vial, weight-based dosing) in the medical record.
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 (common for MPS VI patients with multisystem complications requiring assessment). Routine pre-infusion clinical assessment is bundled.
340B modifiers (JG, TB)
For 340B-acquired Naglazyme, follow your MAC's current 340B modifier policy. Naglazyme's high price makes it a frequent target for 340B program scrutiny.
ICD-10-CM diagnosis codes FY2026 verified May 2026
MPS VI does not have its own dedicated ICD-10-CM code — it falls under the "other mucopolysaccharidoses" bucket along with several other rare MPS subtypes.
| Code | Description | Notes |
|---|---|---|
E76.29 |
Other mucopolysaccharidoses | Primary code for MPS VI. Most coders and most payers use E76.29. The "other" bucket also includes MPS III, IV, VII, IX. Confirm subtype in the medical record. |
E76.2 |
Other mucopolysaccharidoses (parent) | Some payers may accept E76.2 (chapter-level), but E76.29 is the more specific billable code in current FY2026 ICD-10-CM. Use E76.29 by default. |
E76.3 |
Mucopolysaccharidosis, unspecified | Avoid — specificity is required for orphan-drug PA. Confirmed MPS VI should use E76.29. |
E76.0 |
Mucopolysaccharidosis, type I (Hurler/Scheie) | For Aldurazyme — NOT for Naglazyme. |
E76.1 |
Mucopolysaccharidosis, type II (Hunter) | For Elaprase — NOT for Naglazyme. |
Supplementary codes for organ involvement
| System | Common ICD-10 codes |
|---|---|
| Cardiac valve disease | I35.0 aortic stenosis, I34.0 mitral regurgitation, I50.x heart failure |
| Respiratory | J96.9x respiratory failure, G47.33 obstructive sleep apnea, J42 chronic bronchitis |
| Skeletal / joint | M89.9 bone disorder unspecified, M25.5x joint pain, M40.x kyphosis |
| Ophthalmologic | H17.x corneal opacity / scar |
| Neurologic | G91.9 hydrocephalus, G56.0x carpal tunnel |
| Hepatic | R16.0 hepatomegaly, R16.1 splenomegaly, R16.2 hepatosplenomegaly |
Document multisystem involvement. Most payer PAs require evidence of MPS VI's
characteristic multisystem manifestations (skeletal, cardiac, respiratory, ophthalmologic) in addition
to enzyme + genetic confirmation. Pair E76.29 with relevant supplementary codes from organ-specific
evaluations.
Site of care & place of service Verified May 2026
Because of the BOXED anaphylaxis warning and 4-hour infusion duration, Naglazyme is rarely shifted to the home or low-acuity settings. Specialty infusion centers, hospital outpatient infusion clinics, and metabolic/genetics specialty centers are the predominant settings. Many UM programs do NOT enforce site-of-care steering on enzyme replacement therapies because of the safety profile and clinical complexity.
| Setting | POS | Claim form | Payer steering |
|---|---|---|---|
| Hospital outpatient infusion clinic | 22 | UB-04 / 837I | Common & preferred for first 12 mo of therapy at minimum |
| Hospital outpatient (off-campus PBD) | 19 | UB-04 / 837I | Acceptable |
| Metabolic / genetics specialty center | 11 or 22 | CMS-1500 or UB-04 | Preferred for MPS-experienced clinicians |
| Ambulatory infusion suite (AIC) | 49 | CMS-1500 / 837P | Acceptable after tolerance established (typically 6-12 months without reactions) |
| Physician office | 11 | CMS-1500 / 837P | Acceptable if MPS-experienced + emergency response capability |
| Patient home | 12 | CMS-1500 (with home infusion) | Discouraged — some payers permit only after multi-year tolerance and with home-RN + emergency plan; many never approve due to anaphylaxis risk |
Home infusion is high-risk for Naglazyme. Despite some payer programs offering home
ERT for stable MPS patients, the BOXED anaphylaxis warning + 4-hour duration + airway compromise risk
in MPS VI argue against home administration. Confirm payer-specific home-infusion policy and document
risk discussion if pursuing home setting.
Claim form field mapping BioMarin May 2026
From BioMarin RareConnections coverage support and CMS Part B billing guidance.
| Information | CMS-1500 box | Notes |
|---|---|---|
| NPI | 17b | Rendering provider |
| NDC qualifier + 11-digit NDC + UoM + qty | 24A shaded area | N4 + 68135-0020-01 + ML + total mL drawn (5 mL per vial) |
| HCPCS J1458 + JZ (administered, no waste) OR JW (waste line) | 24D (drug line) | Two lines on most claims: administered units + JW waste units |
| Drug units | 24G | Actual mg administered (e.g., 70 for 70 kg patient) |
| CPT 96365 (initial hour) | 24D (admin line 1) | 1 unit |
| CPT 96366 (additional hour) | 24D (admin line 2) | 3 units for standard 4-hour infusion |
| Premedication admin (96367 sequential, 96375 push) | 24D | For diphenhydramine, methylprednisolone, etc. |
| ICD-10 | 21 | E76.29 primary; supplementary organ involvement codes secondary |
| PA number | 23 | Required by all major payers |
Phase 4
Get paid
Diagnostic confirmation (enzyme + gene) is non-negotiable. PA renewals annual.
Payer policy snapshot Reviewed May 2026
All major payers require enzyme assay + ARSB gene mutation confirmation for MPS VI before approving Naglazyme. Specialist (geneticist or metabolic medicine) consultation is also typically required.
| Payer | PA? | Required documentation | Site-of-care UM |
|---|---|---|---|
| UnitedHealthcare Lysosomal Storage Disorders ERT policy |
Yes | MPS VI dx confirmed by ARSB enzyme assay (low activity) + ARSB gene mutation analysis (biallelic pathogenic variants); geneticist or metabolic medicine specialist consultation; baseline 6MWT, urinary GAG, cardiac/pulmonary assessment | Generally not enforced (safety considerations override site steering) |
| Aetna CPB 0729 / Medical Drug policy for ERT |
Yes | Confirmed MPS VI diagnosis (enzyme + gene); specialist Rx; clinical evidence of MPS VI manifestations | Limited — outpatient hospital setting commonly approved |
| BCBS plans Vary by plan; many use industry-standard LSD ERT criteria |
Yes | Generally aligned with FDA label + AAP/MPS-society guidelines; enzyme + gene confirmation; specialist Rx | Plan-specific; most do not steer ERT site of care |
| Medicare (LCDs) | Coverage via MAC LCDs | FDA-labeled indication (MPS VI ages 5+); appropriate diagnosis documentation | N/A |
Annual renewal criteria (typical)
- Continued documented benefit: urinary GAG levels, 6-minute walk distance trajectory, joint range of motion, cardiopulmonary stability
- No serious adverse events necessitating discontinuation
- Continued specialist (geneticist / metabolic medicine) oversight
- Ongoing premedication and infusion safety protocol adherence
Diagnostic confirmation is the most common denial reason on initial PA. Many MPS VI
patients have been diagnosed clinically for years without formal enzyme assay or gene mutation
documentation in the chart. Pull the original diagnostic workup (often from childhood) before
submitting PA — payers want the actual lab result, not a clinician summary.
Medicare reimbursement CMS Q2 2026 (live)
Quarterly ASP from CMS Part B Drug Pricing File. Refreshes automatically each quarter.
Q2 2026 payment snapshot — J1458
Effective April 1 – June 30, 2026 · Based on 4Q25 ASP submissions
ASP + 6%
$513.595
per mg / per unit
70 kg weekly dose
$35,951.65
70 units × ASP+6%
Annual (52 doses)
$1,869,486
70 kg adult · ASP+6%
Annualized cost by patient weight (Q2 2026 ASP+6%): 25 kg pediatric ≈ ~$667,673/year;
40 kg adolescent ≈ ~$1,068,278/year; 70 kg adult ≈ ~$1,869,486/year;
100 kg adult ≈ ~$2,670,694/year. Naglazyme is among the most expensive Part B
drugs on a per-patient annual basis. Sequestration (~2%) reduces actual paid to roughly ASP + 4.3%.
Coverage
No NCD specific to galsulfase. Coverage falls under MAC LCDs for biologics + the generic drug-coverage framework. All MACs cover J1458 for FDA-approved on-label MPS VI use with appropriate ICD-10 documentation, enzyme/genetic confirmation in the medical record, and specialist prescribing.
Code history
- J1458 — permanent code, effective January 1, 2007 (FDA approval was May 2005; pre-permanent-code period used unclassified J3490)
Patient assistance — BioMarin RareConnections BioMarin verified May 2026
- BioMarin RareConnections / Naglazyme Patient Support: 1-866-906-6100 — benefits investigation, prior authorization assistance, appeal support, copay assistance program enrollment
- Naglazyme Copay Assistance Program: commercial copay support for eligible commercially-insured patients (excludes Medicare, Medicaid, federal program patients per OIG guidance)
- BioMarin Patient Assistance Program: free product for uninsured / underinsured patients meeting income requirements
- Foundations: for Medicare patients, refer to PAN, HealthWell, NORD — verify open MPS / lysosomal storage disorder funds quarterly
- NORD MPS-VI fund: National Organization for Rare Disorders may have disease-specific support
- Web: naglazyme.com · biomarin.com/patients
Need to model what a specific patient will actually pay after copay assistance, deductible, coinsurance,
and OOP max for Naglazyme's $1.8M+ annual cost? Run a CareCost Estimate
— J1458 pre-loaded.
Phase 5
Fix problems
Diagnostic gap, missing waste line, wrong admin code (chemo) are the top three.
Common denials & how to fix them
| Denial reason | Common cause | Fix |
|---|---|---|
| Diagnostic confirmation insufficient | PA submitted with clinical diagnosis only; no enzyme assay or gene mutation documentation | Pull original diagnostic workup (often from childhood). Submit ARSB enzyme assay result + ARSB gene mutation analysis. If unavailable, order both before resubmitting. |
| Wrong admin code (96413) | Chemo admin billed instead of therapeutic IV | Resubmit with 96365 + 96366 × 3. Galsulfase is enzyme replacement (not chemo). |
| Missing additional-hour units (96366) | Only 96365 billed for 4-hour infusion | Add 96366 × 3 for hours 2, 3, 4. Document infusion start and stop times in the medical record. |
| JW waste line missing | Partial-vial waste not reported on weight-based dose | Add JW line for discarded units (e.g., 73 kg patient: 73 units administered + 2 units JW for waste). Document weight, vials drawn, mg given, mg discarded. |
| JZ missing on no-waste claim | Patient weight is exact 5 mg multiple but JZ not appended | Resubmit with JZ. Required since 7/1/2023 on every claim with no waste. |
| Wrong ICD-10 (E76.0 / E76.1) | MPS I or MPS II code used for MPS VI patient | Use E76.29. MPS VI does not have its own dedicated code. E76.0 = MPS I (Aldurazyme); E76.1 = MPS II (Elaprase) — will be denied as off-label for Naglazyme. |
| Wrong ERT for MPS subtype | Naglazyme prescribed for MPS I, II, IVA, or VII patient | Verify subtype from genetic testing. Switch to correct ERT: Aldurazyme (MPS I), Elaprase (MPS II), Vimizim (MPS IVA), Mepsevii (MPS VII). |
| No premedication documented | Anaphylaxis-warning drug administered without documented premedication | Document antihistamine + antipyretic administration with time stamps. Bill premedication admin codes (96367/96375) and J-codes (J1200, J2920/J2930, etc.) on the same encounter. |
| Specialist Rx requirement not met | Naglazyme prescribed by non-specialist (e.g., PCP or unrelated specialist) | Re-route through geneticist, metabolic medicine specialist, or pediatric specialist with MPS expertise. Submit specialist consult note with PA. |
| Annual renewal — benefit not documented | Renewal PA submitted without 6MWT, GAG levels, or stability data | Document urinary GAG (compared to baseline / pre-treatment), 6MWT trajectory, joint ROM, cardiopulmonary status. Even modest stability satisfies most payers given disease trajectory without ERT. |
Frequently asked questions
What is the HCPCS code for Naglazyme?
Naglazyme (galsulfase IV) is billed under HCPCS J1458 — "Galsulfase injection."
Each milligram equals one billable unit, so a 1 mg/kg dose for a 70 kg adult is billed as 70 units.
J1458 is permanent and effective January 1, 2007. The drug was FDA-approved May 31, 2005 (BLA 125117)
for mucopolysaccharidosis type VI (MPS VI / Maroteaux-Lamy syndrome).
How many units do I bill for a Naglazyme dose?
Bill the actual mg administered (1 mg/kg actual body weight). For a 70 kg adult: 70 units. For a 25 kg pediatric patient: 25 units. Naglazyme is supplied only in 5 mg / 5 mL single-dose vials, so weight-based dosing produces partial-vial waste in nearly every case unless the weight is an exact multiple of 5 kg. Bill JW for any discarded amount on a separate claim line — CMS requires waste documentation on single-dose container claims since July 2023.
What administration CPT do I use for Naglazyme?
CPT 96365 for the first hour plus 96366 for each additional hour. Naglazyme
is infused over approximately 4 hours per FDA label, so a typical claim includes 96365
× 1 unit + 96366 × 3 units. This is therapeutic (non-chemotherapy) IV
infusion — do NOT use 96413 chemo admin codes. Premedication admin codes (96367 sequential or
96375 IV push) are billed separately.
Do I bill JZ or JW for Naglazyme?
Both apply, depending on whether the calculated dose perfectly matches whole 5 mg vials. If the patient's
weight is an exact multiple of 5 (e.g., 70 kg = 14 vials, no waste), bill JZ. If there is
any partial-vial waste (e.g., 73 kg = 15 vials drawn, 73 mg given, 2 mg discarded), bill the
administered units on the drug line and the discarded units on a separate JW waste line.
One of JZ or JW must be on every J1458 claim.
What is the Medicare reimbursement for J1458?
For Q2 2026, the Medicare Part B payment limit for J1458 is $513.595 per mg (ASP + 6%). The standard 1 mg/kg weekly dose for a 70 kg adult reimburses at approximately $35,951.65 per infusion. Annualized cost (52 weekly doses): approximately $1,869,486 per year for a 70 kg patient. Naglazyme is among the most expensive Part B drugs on a per-patient annual basis. Sequestration (~2%) reduces actual paid to roughly ASP + 4.3%.
Why does Naglazyme have a boxed warning?
Naglazyme carries a BOXED WARNING for anaphylaxis. Severe hypersensitivity reactions, including life-threatening anaphylaxis, have occurred during and within 24 hours after Naglazyme infusions. Reactions include shock, respiratory distress, angioedema, throat tightness, hypoxia, hypotension, urticaria, and bronchospasm. Patients must be premedicated (antihistamines + antipyretics 30-60 min pre-infusion; corticosteroids in patients with prior reactions). Naglazyme must be administered by a healthcare professional in a setting with appropriate medical support (resuscitation equipment, anaphylaxis management capability) immediately available.
What ICD-10 code do I use for MPS VI?
Use E76.29 ("Other mucopolysaccharidoses") as the primary diagnosis. ICD-10-CM does not
provide a unique sub-code for MPS VI / Maroteaux-Lamy syndrome — it falls under the E76.29
"other" category along with several other MPS subtypes. Pair with supplementary codes for organ
involvement: I35.0 (aortic stenosis), I50.x (heart failure), J96.9x (chronic respiratory failure),
H17.x (corneal opacity), G91.9 (hydrocephalus), R16.2 (hepatosplenomegaly) as documented.
What pre-infusion medications are required for Naglazyme?
Per FDA label, premedication is REQUIRED before every Naglazyme infusion: (1) antihistamine (e.g., diphenhydramine 1 mg/kg PO/IV, max 50 mg) 30-60 minutes pre-infusion; (2) antipyretic (e.g., acetaminophen 15 mg/kg PO, max 1 g) 30-60 minutes pre-infusion. Patients with prior infusion reactions or asthma history should additionally receive corticosteroid premedication (e.g., methylprednisolone). See the premedication protocol for billing details.
How does Naglazyme compare to other MPS enzyme replacement therapies?
Each MPS subtype has its own enzyme replacement therapy with a distinct HCPCS code: Naglazyme (galsulfase, J1458) for MPS VI / Maroteaux-Lamy; Aldurazyme (laronidase, J1931) for MPS I / Hurler-Scheie; Elaprase (idursulfase, J1743) for MPS II / Hunter; Vimizim (elosulfase alfa, J1322) for MPS IVA / Morquio A; Mepsevii (vestronidase alfa, J3397) for MPS VII / Sly. All are weekly or biweekly weight-based IV infusions. Confirm exact MPS subtype via enzyme assay AND gene mutation analysis BEFORE submitting PA. See the full MPS treatment landscape.
Reference
Sources & methodology
Every claim on this page is sourced. Methodology and review history below.
Source documents
- DailyMed — NAGLAZYME (galsulfase) Prescribing Information
- FDA Naglazyme label PDF
- Naglazyme.com — BioMarin product site
- BioMarin RareConnections / Patient Support
- CMS — Medicare Part B Drug ASP Pricing File
- SEER CanMED — HCPCS J1458 reference
- UnitedHealthcare — Lysosomal Storage Disorders Enzyme Replacement Therapy Policy
- Aetna CPB 0729 — Enzyme Replacement Therapy for Lysosomal Storage Disorders
- FDA National Drug Code Directory
- NORD — Mucopolysaccharidosis Type VI (Maroteaux-Lamy Syndrome)
- AAP — Mucopolysaccharidoses Health Supervision Guidelines
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
| Element | Cadence | How it's refreshed |
|---|---|---|
| Medicare ASP pricing | Quarterly | Auto-bound to CareCost ASP layer; updates on CMS file release. |
| Payer policies (UHC, Aetna, BCBS LSD ERT policies) | Semi-annual | Manual review against published payer policy documents. |
| HCPCS / CPT / modifier rules | Annual | Reviewed against CMS HCPCS quarterly files and AMA CPT releases. |
| NDC, dosing, FDA label, BOXED warning | Event-driven | Tied to BioMarin label version + FDA label revision date. Naglazyme label changes are infrequent (drug stable since 2005 approval). |
| MPS treatment landscape comparison | Annual | Refreshed when new MPS ERT approvals or HCPCS codes are issued. |
Reviewer
Pending SME review. This page is staff-authored from primary sources (FDA label, CMS,
BioMarin RareConnections, payer LSD ERT policies — all linked above). Editorial review in progress. Until that review is complete, treat this as a draft reference
and verify each cited source for high-stakes claims, particularly the BOXED anaphylaxis warning and
premedication protocol.
Change log
- — Initial publication. ASP data: Q2 2026. Manufacturer source: BioMarin RareConnections (current). FDA label: BLA 125117 (initial 2005 approval, BOXED anaphylaxis warning current). MPS treatment landscape includes all five MPS-specific ERTs on US market.
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. BOXED warning and premedication protocol are taken verbatim from the FDA-approved Naglazyme label. We do not paraphrase from billing-software vendor blogs.