Olipudase Alfa

ASMD is a lysosomal storage disease that results from reduced activity of the enzyme acid sphingomyelinase (ASM), caused by pathogenic variants in the sphingomyelin phosphodiesterase 1 gene. ASM degrades sphingomyelin to ceramide and phosphocholine.

• XENPOZYME is indicated for treatment of non–central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in adult and pediatric patients. XENPOZYME is a hydrolytic lysosomal sphingomyelin-specific enzyme indicated for treatment of non–central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in adult and pediatric patients.

• None. None.contraindicated

See Full Prescribing Information for important recommendations prior to XENPOZYME treatment initiation. ( 2.1 ) Adults: Recommended starting dose is 0.1 mg/kg administered as an intravenous infusion. ( 2.2 ) Pediatrics: Recommended starting dose is 0.03 mg/kg administered as an intravenous infusion. ( 2.3 ) See Full Prescribing Information for the recommended dose escalation and maintenance dosage, dosage modifications to reduce the risk of adverse reactions, and preparation and administration instructions. ( 2.2 , 2.3 , 2.5 , 2.6 , 2.7 ) 2.1 Important Recommendations Prior to XENPOZYME Treatment Initiation Therapy with XENPOZYME should be directed in consultation with physicians knowledgeable in the management of ASMD. In order to avoid dosing errors including overdosage [see Overdosage (10) ] , follow all instructions for dosage and administration. Laboratory Testing Before initiating XENPOZYME: Obtain baseline transaminase (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) levels in all patients within 1 month prior to treatment initiation [see Warnings and Precautions (5.3) ] . Verify pregnancy status in females of reproductive potential [see Use in Specific Populations (8.1 , 8.3) ] . Premedication Prior to XENPOZYME administration, consider premedicating with antihistamines, antipyretics, and/or corticosteroids [see Warnings and Precautions (5.1 , 5.2) ] .

Infusion-Associated Reactions (IARs): If severe IARs occur, discontinue XENPOZYME and initiate appropriate medical treatment. ( 5.2 ) Elevated Transaminases: Assess ALT and AST within one month prior to initiation of XENPOZYME, within 72 hours prior to any infusion during dose escalation, or prior to the next scheduled XENPOZYME infusion upon resuming treatment following a missed dose. ( 5.3 ) Risk of Fetal Malformations During Dosage Initiation or Escalation in Pregnancy: XENPOZYME dosage initiation or escalation, at any time during pregnancy, is not recommended as it may lead to elevated sphingomyelin metabolite levels that may increase the risk of fetal malformations. Advise females of reproductive potential to use effective contraception during treatment and for 14 days after the last dose if XENPOZYME is discontinued. ( 5.4 , 8.1 , 8.3 ) 5.1 Hypersensitivity Reactions Including Anaphylaxis Life-threatening hypersensitivity reactions, including anaphylaxis, have been reported in olipudase alfa-treated patients. One 18-month-old XENPOZYME-treated patient experienced an anaphylactic reaction during the sixth infusion in the dose escalation period in Trial 2 [see Adverse Reactions (6.1) ] . Additionally, a 16-month-old patient with ASMD type A, treated with a version of olipudase alfa manufactured from a different process, experienced two anaphylactic reactions during the fifth and sixth infusions in the dose escalation period; the patient received an immune tolerance induction therapy prior to treatment.

The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity Reactions Including Anaphylaxis [see Warnings and Precautions (5.1) ] Infusion-Associated Reactions (IARs) [see Warnings and Precautions (5.2) ] Elevated Transaminase Levels [see Warnings and Precautions (5.3) ] Most common adverse reactions in adult patients (incidence ≥10%) are headache, cough, diarrhea, hypotension, and ocular hyperemia. ( 6.1 ) Most common adverse reactions in pediatric patients (incidence ≥20%) are pyrexia, cough, diarrhea, rhinitis, abdominal pain, vomiting, headache, urticaria, nausea, rash, arthralgia, pruritus, fatigue, and pharyngitis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genzyme Corporation at 1-800-745-4447 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The pooled safety analysis from 3 clinical trials included a total of 38 XENPOZYME-treated patients (30 adult and 8 pediatric patients) with age range from 1.5 to 59 years old receiving intravenous doses up to 3 mg/kg every 2 weeks [see Clinical Studies (14) ] . The median exposure duration was 2.5 years (range: 0.4 to 3.7 years) in adult patients and 2.7 years (range: 2.5 to 3.2 years) in pediatric patients.

8.1 Pregnancy Risk Summary Based on findings from animal reproduction studies, XENPOZYME may cause embryo-fetal harm when administered to a pregnant female. XENPOZYME dosage initiation or escalation, at any time during pregnancy, is not recommended as it may lead to elevated sphingomyelin metabolite levels that may increase the risk of fetal malformations (see Data ) , [see Clinical Pharmacology (12.2) ] . However, the decision to continue or discontinue XENPOZYME maintenance dosing in pregnancy should consider the female's need for XENPOZYME, the potential drug-related risks to the fetus, and the potential adverse outcomes from untreated maternal ASMD disease. In an embryo-fetal toxicity study in pregnant mice, a rare malformation (exencephaly) was observed in offspring at an exposure less than the exposure at the maximum recommended human dose (MRHD) of olipudase alfa-rpcp (see Data ) . There are no available data on XENPOZYME use in pregnant females to evaluate for a drug associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Advise the pregnant female of the potential risk to the fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, miscarriage, or other adverse outcomes. In the U.S.

Metabolism

In adult patients with ASMD, the mean (SD) maximum plasma olipudase alfa-rpcp concentration (C max ) and area under the concentration-time curve (AUC) at steady state were 30 (5) mcg/mL and 607 (120) mcg∙h/mL, respectively, at the recommended maintenance dose of 3 mg/kg administered once every 2 weeks. Olipudase alfa-rpcp C max and AUC increase proportionally over a dose range of 0.1 to 3 mg/kg (0.03 to 1 times the approved recommended maintenance dose).

Cases of overdosage with XENPOZYME have been reported in pediatric patients during dose escalation. Some patients experienced serious adverse reactions including death within 24 hours of initial dose [see Warnings and Precautions (5.2) ] . The clinical findings included fever, hypotension, gastrointestinal bleeding, marked elevation in liver tests, metabolic acidosis, respiratory failure, and vomiting. There is no known specific antidote for XENPOZYME overdosage. In the event of overdosage, immediately stop the infusion, and monitor the patient closely in a hospital setting for the development of hypersensitivity reactions and IARs including acute phase reactions. For the management of adverse reactions, see Warnings and Precautions (5.1 , 5.2 , 5.3) and Adverse Reactions (6.1) .

• Aug 31, 2022BLABLA761261Genzyme Corp

1. 1Headache109.0%
2. 2Incorrect Dose Administered109.0%
3. 3Fatigue87.2%
4. 4Nausea76.3%
5. 5Weight Increased76.3%
6. 6Condition Aggravated54.5%
7. 7Erythema54.5%
8. 8Illness54.5%
9. 9Pyrexia54.5%
10. 10Sinusitis54.5%
11. 11Nasopharyngitis43.6%
12. 12Urticaria43.6%
13. 13Vomiting43.6%
14. 14Weight Decreased43.6%
15. 15Alanine Aminotransferase Increased32.7%

The 7 most recently updated of 7 ClinicalTrials.gov registrations naming Olipudase Alfa as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study to Evaluate Safety and Tolerability of Olipudase Alfa in Pediatric and Adult Participants With Acid Sphingomyelinase Deficiency (ASMD) Who Completed the DFI12712 or the LTS13632 Study in France
  Completed · Phase 2 · Interventional · 3 enrolled · Sanofi
  NCT06949358updated 2026-04-13
• A Real-world Long-term Safety and Immunogenicity Study of Olipudase Alfa Therapy in Pediatric Patients Less Than 2 Years of Age With Acid Sphingomyelinase Deficiency (ASMD)
  Recruiting · Observational · 10 enrolled · Sanofi
  NCT06192576updated 2025-10-31
• Data Analysis of Adult and Pediatric Participants With Acid Sphingomyelinase Deficiency (ASMD) on Early Access to Olipudase Alfa in France
  Completed · Observational · 40 enrolled · Sanofi
  NCT05359276updated 2025-02-06
• Efficacy, Safety, Pharmacodynamic, and Pharmacokinetics Study of Olipudase Alfa in Patients With Acid Sphingomyelinase Deficiency
  Completed · Phase 2 · Phase 3 · Interventional · 36 enrolled · Genzyme, a Sanofi Company
  NCT02004691updated 2024-11-07
• A Long-Term Study of Olipudase Alfa in Patients With Acid Sphingomyelinase Deficiency
  Completed · Phase 2 · Interventional · 25 enrolled · Genzyme, a Sanofi Company
  NCT02004704updated 2024-07-03
• Compassionate Use Program for Olipudase Alfa Enzyme Replacement Therapy for Patients With Chronic Acid Sphingomyelinase Deficiency (ASMD)
  Approved for marketing · Expanded access · Sanofi
  NCT04877132updated 2022-09-19
• Safety, Tolerability, PK, and Efficacy Evaluation of Repeat Ascending Doses of Olipudase Alfa in Pediatric Patients <18 Years of Age With Acid Sphingomyelinase Deficiency
  Completed · Phase 1 · Phase 2 · Interventional · 20 enrolled · Genzyme, a Sanofi Company
  NCT02292654updated 2022-03-23

Frequently asked questions

How does Olipudase Alfa work?

ASMD is a lysosomal storage disease that results from reduced activity of the enzyme acid sphingomyelinase (ASM), caused by pathogenic variants in the sphingomyelin phosphodiesterase 1 gene. ASM degrades sphingomyelin to ceramide and phosphocholine.

What is Olipudase Alfa used for?

According to FDA labeling, Olipudase Alfa carries indications including: XENPOZYME is indicated for treatment of non–central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in adult and pediatric patients. XENPOZYME is a hydrolytic lysosomal sphingomyelin-specific enzyme indicated for treatment of non–central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in adult and pediatric patients.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Olipudase Alfa?

Olipudase Alfa is classified as Enzymes.

What are the brand names for Olipudase Alfa?

Olipudase Alfa is marketed under brand names including Xenpozyme.

What are the contraindications for Olipudase Alfa?

Olipudase Alfa labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.