Olipudase alfa

Table of contents

• What is olipudase alfa?
• How does olipudase alfa work?
• Which conditions is olipudase alfa used or studied for?
• How is olipudase alfa given?
• What do the clinical trials show?
• What side effects are known?

What is olipudase alfa?

Olipudase alfa, also known by the brand name Xenpozyme, is a protein-based medicine that replaces an enzyme missing in people with acid sphingomyelinase deficiency (ASMD).^[1] It is a hydrolytic lysosomal sphingomyelin-specific enzyme, meaning it breaks down a fatty substance called sphingomyelin inside cells.^[2] In the United States, olipudase alfa was first approved in 2022 under the name Xenpozyme for treating non-central nervous system manifestations of ASMD in adults and children.^[2] In the European trial records, it appears as an investigational substance with no marketing authorisation listed, and it has orphan designation because ASMD is a rare disease.^[1] The product is supplied by Genzyme Corporation.^[1]

How does olipudase alfa work?

People with ASMD have a defect in the enzyme acid sphingomyelinase, which normally breaks down sphingomyelin. When the enzyme is missing or not working, sphingomyelin builds up in cells and organs, causing damage. Olipudase alfa is a laboratory-made version of this enzyme. When given by infusion, it helps break down the accumulated sphingomyelin, which is the underlying problem in ASMD.^[5] This approach is called enzyme replacement therapy.^[5]

Which conditions is olipudase alfa used or studied for?

• Acid sphingomyelinase deficiency (ASMD) — a rare inherited condition also known as Niemann-Pick disease, in which a fatty substance builds up in organs such as the liver, spleen and lungs. Olipudase alfa is used for the non-central nervous system manifestations of this condition.^[2]

How is olipudase alfa given?

Olipudase alfa is given as an intravenous infusion, meaning it is delivered directly into a vein.^[1] It comes as a powder that is made into a solution for infusion.^[1] The US prescribing information gives a starting dose of 0.1 mg per kilogram of body weight for adults and 0.03 mg per kilogram for children, with a dose escalation schedule described in the full label.^[2] In the UK medicines database, olipudase alfa is listed as a 20 mg powder for solution for infusion in vials.^[3]

What do the clinical trials show?

The EU Clinical Trials register contains one trial of olipudase alfa, a completed Phase 2 study in France.^[1] The trial enrolled 3 participants, both children and adults, with acid sphingomyelinase deficiency who had already completed one of two earlier studies (DFI12712 or LTS13632).^[1] The main outcome measured was the number of adverse events and serious adverse events, to assess safety and tolerability.^[1] The study continued until olipudase alfa reimbursement was granted in France or for up to 5 years, whichever came first.^[1] The dose used in the trial was 3 mg per kilogram given intravenously.^[1]

What side effects are known?

The US prescribing information for Xenpozyme carries a boxed warning about hypersensitivity reactions, including anaphylaxis, a severe allergic reaction.^[2] It states that appropriate medical monitoring and support measures, including cardiopulmonary resuscitation equipment, should be readily available during treatment.^[2] If a severe hypersensitivity reaction occurs, the infusion should be stopped immediately and appropriate medical treatment started.^[2] The Scottish Medicines Consortium noted that there are limited data in small numbers of patients, with no data to support a mortality benefit, and that the cost in relation to its benefits is exceptionally high.^[4]