FDA Approves Olipudase Alfa-rpcp for Acid Sphingomyelinase Deficiency

Drug Topics JournalDrug Topics November 2022
Volume 166
Issue 11

Acid sphingomyelinase deficiency is a rare, progressive genetic disease associated with significant morbidity and mortality.

On August 31, 2022, the FDA approved olipudase alfa-rpcp (Xenpozyme) for intravenous (IV) infusion in pediatric and adult patients with acid sphingomyelinase deficiency (ASMD),1 a rare genetic disease that causes premature death due to the accumulation of a complex lipid called sphingomyelin. Olipudase alfa-rpcp is an enzyme replacement therapy and provides an exogenous source of ASM. It is the first approved medication to treat symptoms that are not related to the central nervous system in patients with ASMD. Olipudase alfa-rpcp received fast track, breakthrough therapy, priority review, and orphan drug designations from the FDA.1


Investigators evaluated the efficacy of olipudase alfa-rpcp across 3 clinical trials. The first, ASCEND (NCT02004691), a multicenter, randomized, double-blinded, placebo-controlled, repeat-dose phase 2/3 study, evaluated adults with ASMD in 2 groups: a treatment group, receiving olipudase alfa-rpcp for 104 weeks (n = 13), and the placebo group (n = 18). At week 52, patients in the placebo group crossed over to receive olipudase alfa-rpcp treatment to reach the targeted maintenance dose of 3 mg/kg.

By week 104, patients who were initially in the placebo group had received olipudase alfa-rpcp for 52 weeks and demonstrated the following mean changes from baseline: predicted diffusion capacity of the lungs for carbon monoxide (DLco) increased by 26.8%; spleen volume reduced by 36.5%; liver volume reduced by 29.5%; and platelet count increased by 19.5%.

Patients in the previous olipudase alfa-rpcp group demonstrated improvement from baseline in the following parameters: predicted DLco increased by 34.1%; spleen volume reduced by 48.3%; liver volume reduced by 31.7%; and platelet count increased by 24%.

Trial 2, ASCEND-Peds (NCT02292654), enrolled 8 pediatric patients who received an IV infusion of olipudase alfa every 2 weeks over a 64-week period. During a 6-month extension study (Trial 3; NCT02004704), efficacy analyses showed continued improvements in the 3 patients evaluated for percent predicted DLco, the 6 patients evaluated for platelet counts, and all 8 patients evaluated for spleen and liver volumes, compared with baseline.


Two pediatric patients reported a serious adverse event (anaphylactic reaction). The most frequently reported adverse drug reactions in adults were headache, cough, diarrhea, hypotension, and ocular hyperemia. In pediatric patients, these reactions included pyrexia, cough, diarrhea, rhinitis, abdominal pain, vomiting, headache, urticaria, nausea, rash, arthralgia, pruritus, fatigue, and pharyngitis.

Treatment-related serious adverse events, hypersensitivity reactions including anaphylaxis, and infusion-associated reactions occurred within 24 hours of infusion and were observed in a higher percentage of pediatric patients than adult patients.

Drug Administration

Olipudase alfa-rpcp is administered via IV infusion every 2 weeks for adult and pediatric patients. In adults, the recommended starting dose is 0.1 mg/kg on day 1/week 0. The recommended maintenance dose is 3 mg/kg every 2 weeks. The dose escalation regimen is as follows: 0.3 mg/kg at week 2 and week 4; 0.6 mg/kg at week 6 and week 8; 1 mg/kg at week 10; 2 mg/kg at week 12; and 3 mg/kg at week 14 and thereafter.

In pediatric patients, the recommended starting dose is 0.03 mg/kg on day 1/week 0. The recommended maintenance dose is 3 mg/kg every 2 weeks. The dose escalation regimen is as follows: 0.1 mg/kg at week 2; 0.3 mg/kg at week 4 and week 6; 0.6 mg/kg at week 8 and week 10; 1 mg/kg at week 12; 2 mg/kg at week 14; and 3 mg/kg at week 16 and thereafter.

Reconstituted olipudase alfa-rpcp vials not used immediately and diluted solutions not to be administered immediately should be refrigerated at 2 to 8 °C (36-46 °F) for up to 24 hours, or at room temperature at 20 to 25 °C (68-77 °F) for up to 12 hours.


  1. FDA approves first treatment for acid sphingomyelinase deficiency, a rare genetic disease. News release. FDA. August 31, 2022. Accessed October 2, 2022. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-acid-sphingomyelinase-deficiency-rare-genetic-disease
  2. Xenpozyme. Prescribing information. Genzyme; 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761261s000lbl.pdf

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