Medical Drug Criteria (MDC)

Policy Num:     P1.001.015
Policy Name:   XENPOZYME^® (olipudase alfa-rpcp)
Policy ID:         [P1.001.015] [Ac/L/ M+/ P +] 

Last Review:       September 22, 2025
Next Review:      September 20, 2026
 

Related MDC: NONE

XENPOZYME^® (olipudase alfa-rpcp) 

Summary

XENPOZYME® (olipudase alfa-rpcp) is an enzyme replacement therapy (ERT) for the treatment of non-CNS manifestations of ASMD in both adults and pediatric patients. Mechanism: Recombinant human acid sphingomyelinase that hydrolyzes accumulated sphingomyelin in lysosomes, reducing lipid storage. Disease background: ASMD (Niemann-Pick disease types A/B) is an autosomal recessive lysosomal storage disorder caused by SMPD1 gene mutations, leading to deficient ASM activity, sphingomyelin buildup, hepatosplenomegaly, pulmonary dysfunction, and systemic morbidity. Clinical trials (ASCEND, ASCEND-Peds): demonstrated significant reductions in spleen/liver volume and improvements in pulmonary function (DLCO). FDA Indication: Approved for non-CNS manifestations of ASMD (July 2022; PI revised December 2023).

Objective

Ensure medically necessary and evidence-based use of XENPOZYME. Provide payer criteria consistent with FDA-approved labeling and clinical guidelines. Define clear initiation, continuation, and exclusion standards.

Policy Statements

XENPOZYME may be considered medically necessary for treatment of non-CNS manifestations of ASMD when patient-specific criteria are met.

Policy Guidelines

Authorization period: Up to 12 months initially.
 
Use limitation: Must be prescribed by a specialist experienced in metabolic/genetic disorders (e.g., geneticist, hepatologist, neurologist).
 
Monitoring: Baseline and follow-up imaging (spleen volume), pulmonary function (DLCO), and hematologic parameters recommended.

DOSAGE/ADMINISTRATION

For treatment of non-central nervous system (non-CNS) manifestations of ASMD): 

•    Adults: Recommended starting dose is 0.1 mg/kg administered as an intravenous infusion, titrate every 2 weeks to 3 mg/kg.

•    Pediatrics: Recommended starting dose is 0.03 mg/kg administered as an intravenous infusion, titrate every 2 weeks to 3 mg/kg.

REQUIRED MEDICAL INFORMATION

Initial Therapy

a) Initiation of olipudase alfa (Xenpozyme) meets the definition of medical necessity when ALL of the following criteria are met: 

1.    Member is diagnosed with acid sphingomyelinase deficiency (ASMD)

2.    Member has a mutation in the sphingomyelin phophodiesterase-1 (SMPD1) gene (laboratory documentation must be provided)

3.    Member has a deficiency of acid sphingomyelinase as measured in peripheral leukocytes, cultured fibroblasts, or lymphocytes – laboratory documentation must be provided 

4.    Member has a spleen volume greater than or equal to 5 multiples of normal (MN) measured by magnetic resonance imaging (MRI) 

5.    Member has a diffuse capacity of the lung for carbon monoxide less than or equal to 70% of the predicted normal value 

6.    Olipudase is prescribed by specializing in the treatment of ASMD (e.g., neurologist, hepatologist, geneticist)

Renewal Approval Criteria 

a)    Continuation of olipudase alfa (Xenpozyme) meets the definition of medical necessity when ALL of the following criteria are met: 

1.    The member has previously met all indication-specific initial criteria 

2.    Olipudase is prescribed by a provider specializing in the treatment of ASMD (e.g., neurologist, hepatologist, geneticist) 

3.    Dose does not exceed 3 mg/kg every 2 weeks

Background

ASMD: Rare, progressive, multisystem disorder with hepatosplenomegaly, interstitial lung disease, growth retardation, and early mortality in severe forms. 

NPD A/B distinction: Type A has rapid neurologic decline and early lethality; Type B presents with systemic (non-CNS) disease and longer survival.

Therapeutic gap: Prior to olipudase alfa, treatment was supportive only. XENPOZYME is the first disease-modifying therapy for ASMD.

Regulatory Status

FDA: Approved July 2022; PI revised December 2023.

EMA/International: Approved in EU and Japan for non-CNS ASMD.

Orphan Drug: Yes, under FDA Orphan designation.

EXCLUSION CRITERIA

None beyond FDA contraindications (e.g., hypersensitivity to olipudase alfa or excipients).

BENEFIT APPLICATION

Benefits are determined by the group contract, member benefit booklet, and/or individual subscriber certificate in effect at the time services were rendered. Benefit products or negotiated coverages may have all or some of the services discussed in this medical policy excluded from their coverag. 

OTHER CRITERIA

NONE 

Rationale

Efficacy: ASCEND Phase II/III trial demonstrated ≥30% reduction in spleen volume and clinically meaningful DLCO improvement.

Safety: Most common adverse events: infusion-related reactions, headache, nausea, diarrhea, cough, and pyrexia.

Clinical consensus: ERT recommended as standard for ASMD with symptomatic organ involvement.

Supplemental Information

Dose titration: Slow up-titration required to reduce risk of infusion-related reactions.

No CNS benefit: Does not cross the blood–brain barrier; neurologic manifestations remain unaddressed.

Lifelong therapy: Continuous ERT required for sustained benefit.

Practice Guidelines and Position Statements

NORD (2023): Supports ERT with olipudase alfa as standard of care for ASMD.

References

1. Clinical Pharmacology. Gold Standard, 2022.

2. ClinicalTrials.gov. Accessed 2023.

3. Cox GF, et al. JIMD Rep. 2018;41:119-129.

4. DRUGDEX® System. Micromedex, 2023.

5. NORD. Acid sphingomyelinase deficiency, 2022. 

6. XENPOZYME PI. Genzyme Corp.; Revised December 2023.

Codes

Applicable Modifiers

N/A

Policy History