Last Review Date: 08/08/2023

Date of Origin: 10/03/2022

Dates Reviewed: 10/2022, 02/2023, 08/2023

1. Length of Authorization

Coverage will be provided for 12 months and may be renewed.

2. Dosing Limits

A. Quantity Limit (max daily dose) [NDC Unit]:

• Xenpozyme 4 mg single-dose vial: 4 vials per 14 days
• Xenpozyme 20 mg single-dose vial: 17 vials per 14 days

B. Max Units (per dose and over time) [HCPCS Unit]:

• 340 billable units (340 mg) every 14 days

3. Initial Approval Criteria ¹

Coverage is provided in the following conditions:

• 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; AND
• 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 (height Z-score and skeletal maturation are relevant for pediatric patients); AND

Universal Criteria ¹

• Documented baseline transaminase (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) levels within 1 month prior to treatment initiation, within 72 hours prior to any infusion during dose escalation, and periodically throughout therapy; AND
• Patient should not require invasive ventilatory support OR non-invasive ventilatory support while awake and for >12 hours a day (Note: Patients requiring ventilatory support will be reviewed on a case-by-case basis); AND

Acid Sphingomyelinase Deficiency (ASMD) (Niemann-Pick Disease) † Ф ^1,6

• Patient has a definitive diagnosis of ASMD as confirmed by the following:
  • Detection of biallelic pathogenic mutations in the SMPD1 gene by molecular genetic testing; OR
  • Deficiency of acid sphingomyelinase enzyme activity <10% of controls as measured in peripheral leukocytes, cultured fibroblasts, or lymphocytes; AND
• 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 as well as signs/symptoms may not be conclusive in infants therefore requests will be evaluated on a case-by-case basis); AND
• Therapy will be used for non-CNS manifestations of disease (Note: Xenpozyme is not expected to cross the blood-brain barrier or modulate CNS manifestations of disease)

† FDA-approved indication(s); ‡ Compendia recommended indication(s); Ф Orphan Drug

4. Renewal Criteria ¹

Coverage can be renewed based on the following criteria:

• Patient continues to meet universal and other indication-specific relevant criteria such as concomitant therapy requirements (not including prerequisite therapy), performance status, etc. identified in section III; AND

• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: anaphylaxis and severe hypersensitivity reactions, severe infusion-associated reactions, severely elevated liver transaminases, etc.; AND
• Patient has not experienced progressive/irreversible severe cognitive impairment; AND
• Disease response with treatment as defined by improvement or stability from pre-treatment baseline by the following:
  • Improvement in or stability in the percent predicted diffusion capacity of the lungs for carbon monoxide (DLco) or other age-appropriate pulmonary function testing; OR
  • Improvement in or stability of spleen and/or liver volumes; OR
  • Reduction in plasma lyso-sphingomyelin; OR
  • Improvement in or stability of platelet count; OR
  • Improvement in linear growth progression as measured by mean height Z-scores (pediatric patients only)

5. Dosage/Administration ¹

6. Billing Code/Availability Information

HCPCS Code:

• J0218 – Injection, olipudase alfa-rpcp, 1 mg; 1 billable unit = 1 mg

NDC:

• Xenpozyme 4 mg lyophilized powder for reconstitution in a single-dose vial: 58468-0051-xx
• Xenpozyme 20 mg lyophilized powder for reconstitution in a single-dose vial: 58468-0050-xx

7. References

1. Xenpozyme [package insert]. Cambridge, MA; Genzyme Corporation, Inc.; July 2023. Accessed August 2023.
2. Wasserstein M, Lachmann R, Hollak C, et al. A randomized, placebo-controlled clinical trial evaluating olipudase alfa enzyme replacement therapy for chronic acid sphingomyelinase deficiency (ASMD) in adults: One-year results. Genetics in Medicine, vol 24, Iss 7, 2022, 1425-1436. ISSN 1098-3600, https://doi.org/10.1016/j.gim.2022.03.021.
3. Diaz GA, Jones SA, Scarpa M, et al. One-year results of a clinical trial of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency. Genet Med. 2021 Aug;23(8):1543-1550. doi: 10.1038/s41436-021-01156-3. Epub 2021 Apr 19.
4. Thurberg BL, Diaz GA, Lachmann RH, et al. Long-term efficacy of olipudase alfa in adults with acid sphingomyelinase deficiency (ASMD): Further clearance of hepatic sphingomyelin is associated with additional improvements in pro- and anti-atherogenic lipid profiles after 42 months of treatment. Mol Genet Metab. 2020 Sep - Oct;131(1-2):245-252. doi: 10.1016/j.ymgme.2020.06.010. Epub 2020 Jun 24.
5. Wasserstein MP, Diaz GA, Lachmann RH, et al. Olipudase alfa for treatment of acid sphingomyelinase deficiency (ASMD): safety and efficacy in adults treated for 30 months. J Inherit Metab Dis. 2018 Sep;41(5):829-838. doi: 10.1007/s10545-017-0123-6. Epub 2018 Jan 5.
6. Wasserstein MP, Schuchman EH. Acid Sphingomyelinase Deficiency. In: Adam MP, Everman DB, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Initial Posting: Dec 7, 2006; Last Update: Feb 25, 2021. Accessed Jan 6, 2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1370/.

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determination (NCD), Local Coverage Determinations (LCDs), and Local Coverage Articles (LCAs) may exist and compliance with these policies is required where applicable. They can be found at: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications may be covered at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/LCA): N/A