CurrentNeighborhood Health Plan of Rhode IslandPolicy N/A

Xenpozyme (olipudase alfa) intravenous

Policy governs coverage, dosing, renewal, and billing for Xenpozyme (olipudase alfa) for treatment of non‑CNS manifestations of acid sphingomyelinase deficiency (ASMD) across Medicaid, Commercial, and Medicare lines.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyXenpozyme (olipudase alfa) intravenous

Policy CodePolicy N/A

Change TypeNo material change

Effective DateAug 1, 2023

Next Review Date

Key ActionSubmit prior authorization for 6 months with baseline measures and diagnosis confirmation; include required labs, imaging, genetic or enzyme testing, and current weight for dosing.

POLICY UPDATE CHANGES

No material clinical/coverage changes

6 moInitial Authorization Length

340Max dose per 14 days (mg)

3 mg/kgMax mg/kg per 2 weeks

E75.241, E75.244Covered ICD-10 diagnoses

Coverage Summary

Coverage stance: covered_with_criteria for Xenpozyme (olipudase alfa) for treatment of non‑CNS manifestations of acid sphingomyelinase deficiency (ASMD) across Medicaid, Commercial, and Medicare lines. Scope: policy governs coverage, dosing, renewal, and billing for Xenpozyme for non‑CNS ASMD. Authorization length: coverage is provided for 6 months and may be renewed every 6 months. Effective date: 2023-08-01. Last review date: 2025-06-04.

Initial Therapy Criteria

Initial Approval Criteria

Coverage is provided when ALL of the following are met:

ALL of the following

Reproductive/pregnancy and baseline documentation
- Females of reproductive potential will have pregnancy status verified prior to start of therapy and will use effective contraception during treatment and for 14 days after the last dose if therapy is discontinued
- Baseline measures: Patient has documented baseline measures (necessary for renewal) of: percent predicted diffusion capacity of the lungs for carbon monoxide (DLco) or other age-appropriate pulmonary function testing, spleen volume, liver volume, plasma lyso-sphingomyelin, and/or platelet count
- Pediatric baseline measures
  - For pediatric patients ONLY: height Z-score and skeletal maturation
- Liver tests: Documented baseline transaminase (ALT and AST) levels within 1 month prior to treatment initiation, within 72 hours prior to any infusion during dose escalation, and periodically throughout therapy
Prescriber and dosing requirements
- Specialist involvement: Medication is prescribed by, or in consultation with, a specialist familiar with the treatment of lysosomal storage disorders
- Dose limit: Dose does not exceed 3 mg/kg every 2 weeks≤ 3 mg/kg every 2 weeks
  Max units per dose 340 mg every 14 days (HCPCS J0218, 1 mg per billable unit)
- Weight documentation: Documentation of patient's current weight (kg)
  Use adjusted body weight for BMI > 30 per policy
Diagnosis confirmation (ALL of the following OR options)
- Genetic confirmation: Patient has a definitive diagnosis of ASMD as confirmed by detection of biallelic pathogenic mutations in the SMPD1 gene by molecular genetic testing
- Enzyme assay alternative: Deficiency of acid sphingomyelinase enzyme activity <10% of controls as measured in peripheral leukocytes, cultured fibroblasts, or lymphocytes< 10% of controls
Clinical diagnosis and scope: Patient has a clinical diagnosis consistent with Niemann-Pick disease type B (NPD-B) or A/B (NPD-A/B). Note: NPD-A (infantile neurovisceral ASMD) has not been studied; genotype-phenotype correlations and signs/symptoms may be inconclusive in infants and requests will be evaluated on a case-by-case basis
Therapy will be used for non-CNS manifestations of disease (Xenpozyme is not expected to cross the blood-brain barrier or modulate CNS manifestations)

Exclusionary (coverage will NOT be provided if ANY are present)

Acute neurologic decline: Patient has acute or rapidly progressive neurologic abnormalities
Ventilatory support: Patient requires invasive ventilatory support OR requires non-invasive ventilatory support while awake and for >12 hours a day
Low platelets: Platelet count <60 × 10^3/µL< 60 × 10^3/µL
Abnormal coagulation: International normalized ratio (INR) >1.5> 1.5

Continuation Therapy Criteria

Renewal Criteria

Coverage may be renewed every 6 months when ALL of the following are met:

ALL of the following

Continuation of initial criteria: Patient continues to meet initial and other indication-specific relevant criteria identified in the policy
Toxicity: Absence of unacceptable toxicity from the drug (examples: anaphylaxis, severe hypersensitivity, severe infusion-associated reactions, severely elevated liver transaminases)
Cognitive status: Patient has not experienced progressive/irreversible severe cognitive impairment
Disease response (ONE of the following)
- Pulmonary response: Improvement in or stability in percent predicted DLco or other age-appropriate pulmonary function testing
- Organ volumes: Improvement in or stability of spleen and/or liver volumes
- Biomarker: Reduction in plasma lyso-sphingomyelin
- Platelet response: Improvement in or stability of platelet count
- Pediatric growth: Improvement in linear growth progression as measured by mean height Z-scores (pediatric patients only)

Authorization length: Coverage authorization provided for 6 months and may be renewed every 6 months6 months

Provider Actions & Authorization Requirements

Prior Authorization

Prior Authorization and Duration

Coverage authorization provided for 6 months and may be renewed every 6 months; documentation of baseline measures and diagnosis confirmation must be submitted with requests.

Coverage authorization: 6 months; may be renewed every 6 months
Submit documentation of baseline measures and diagnosis confirmation with requests

Documentation Required

Baseline and Ongoing Lab/Imaging Documentation

Provide baseline percent predicted DLco or other age-appropriate pulmonary function testing, spleen and liver volumes, plasma lyso-sphingomyelin, platelet count, and baseline ALT/AST within 1 month prior to initiation. Obtain ALT/AST within 72 hours prior to any infusion during dose escalation and periodically throughout therapy.

Baseline percent predicted DLco or other PFTs
Spleen volume and liver volume
Plasma lyso-sphingomyelin
Platelet count
Baseline ALT and AST within 1 month prior to initiation
ALT and AST within 72 hours prior to infusions during dose escalation and periodically thereafter

Documentation Required

Genetic or Enzyme Confirmation

Submit confirmation of diagnosis by either molecular genetic testing demonstrating detection of biallelic pathogenic SMPD1 mutations OR demonstration of acid sphingomyelinase enzyme activity <10% of controls measured in peripheral leukocytes, cultured fibroblasts, or lymphocytes.

Molecular genetic testing showing biallelic pathogenic SMPD1 mutations
Acid sphingomyelinase enzyme activity <10% of controls (peripheral leukocytes, cultured fibroblasts, or lymphocytes)

Billing Rule

Dose and Billing Units

Bill using HCPCS code J0218. One billable unit = 1 mg. J0218 = 1 mg per unit. Max units per dose: 340 units (340 mg) every 14 days. Do not exceed 3 mg/kg every 2 weeks.

HCPCS code: J0218 — Injection, olipudase alfa, 1 mg (1 billable unit = 1 mg)
Max 340 billable units (340 mg) every 14 days
Do not exceed 3 mg/kg every 2 weeks

Documentation Required

Weight Documentation

Provide current patient weight (kg) to calculate weight-based dosing. For patients with BMI > 30, use adjusted body weight per policy: adjusted body weight (kg) = (actual height in meters)^2 x 30.

Current patient weight (kg) required
Use adjusted body weight for BMI > 30 using policy formula: (height in m)^2 x 30

Documentation Required

Contraception Verification

Verify pregnancy status prior to initiation and document effective contraception for females of reproductive potential during treatment and for 14 days after the last dose if therapy is discontinued.

Pregnancy status verification prior to start of therapy
Documentation of effective contraception during treatment and for 14 days after last dose if discontinued

Denial Risk

Denial Risk for Exclusionary Conditions

Claims may be denied if any exclusionary conditions are present. Exclusionary conditions include acute or rapidly progressive neurologic abnormalities; requirement for invasive ventilatory support or non-invasive support while awake >12 hours/day; platelet count <60 × 10^3/µL; INR >1.5; ALT or AST >250 IU/L; total bilirubin >1.5 mg/dL.

Acute or rapidly progressive neurologic abnormalities
Invasive ventilatory support OR non-invasive ventilatory support while awake >12 hours/day
Platelet count <60 × 10^3/µL
International normalized ratio (INR) >1.5
ALT or AST >250 IU/L
Total bilirubin >1.5 mg/dL

Clinical Evidence

DLcoMean % change from baseline to week 52 (ASCEND/ASCEND‑Peds)

SpleenMean % change in spleen volume from baseline to week 52

LiverMean % change in liver volume from baseline to week 52

PlateletsMean % change in platelet count from baseline to week 52

Height ZMean change in height Z‑scores at week 52 (pediatrics)

Safety signal summary: the most frequently reported adverse reactions in adults (incidence ≥10%) include headache, cough, diarrhea, hypotension, and ocular hyperemia. Clinical evidence from the ASCEND (adult randomized, placebo-controlled trial) and ASCEND‑Peds (pediatric open-label trial) demonstrated statistically significant improvements in mean percent change from baseline to week 52 for DLco, spleen volume, liver volume, platelet count, and in pediatrics also height Z‑scores.

Background & Definitions

Background: Xenpozyme (olipudase alfa) is an enzyme replacement therapy indicated for the treatment of non‑CNS manifestations of ASMD. The agent is noted in the policy as not expected to cross the blood‑brain barrier and therefore is intended to treat peripheral (non‑CNS) disease manifestations. Key clinical trials include ASCEND (phase 2/3 randomized, double‑blind, placebo‑controlled adult trial) and ASCEND‑Peds (phase 1/2 open‑label pediatric trial); both demonstrated statistically significant benefit on the primary endpoints including percent predicted DLco, spleen and liver volumes, platelet counts, and in pediatrics height Z‑scores.

Term	Definition
Adjusted body weight	Calculated as (actual height in meters)^2 x 30 for patients with BMI > 30 to determine dosing weight per policy
Billable unit	HCPCS J0218: 1 billable unit = 1 mg

OpenPayer

Xenpozyme (olipudase alfa) intravenous

Coverage Summary

Initial Therapy Criteria

Continuation Therapy Criteria

Provider Actions & Authorization Requirements

Applicable Codes

Clinical Evidence

Background & Definitions

Revision History

E75.241	Niemann-Pick disease type B
E75.244	Niemann-Pick disease type A/B