General Information

Xenpozyme (olipudase alfa-rpcp) is a hydrolytic lysosomal sphingomyelin-specific enzyme.

Xenpozyme is specifically indicated for the treatment of non-central nervous system (non-CNS) manifestations of acid sphingomyelinase deficiency (ASMD) in adult and pediatric patients. 

Xenpozyme is supplied as an injection for intravenous administration.

• Prior to initiating treatment, verify pregnancy status in females of reproductive potential and obtain baseline transaminase levels.
• Consider pretreating with antihistamines, antipyretics, and/or corticosteroids.

Adults: Recommended starting dose is 0.1 mg/kg administered as an intravenous infusion. In order to reduce the risk of hypersensitivity and infusion-associated reactions or elevated transaminase levels, Xenpozyme should be administered in the dose escalation regimen outlined in the drug prescription label. Administer Xenpozyme via intravenous infusion every 2 weeks. The recommended maintenance dosage in adults is 3 mg/kg via intravenous infusion every 2 weeks.

Pediatrics: Recommended starting dose is 0.03 mg/kg administered as an intravenous infusion. In order to reduce the risk of hypersensitivity and infusion-associated reactions or elevated transaminase levels, Xenpozyme should be administered in the dose escalation regimen outlined in the drug prescription label. Administer Xenpozyme via intravenous infusion every 2 weeks. The recommended maintenance dosage in adults is 3 mg/kg via intravenous infusion every 2 weeks.

Mechanism of Action

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. The deficiency of ASM causes an intra-lysosomal accumulation of sphingomyelin (as well as cholesterol and other cell membrane lipids) in various tissues.

Xenpozyme provides an exogenous source of ASM. Xenpozyme is not expected to cross the blood-brain barrier or modulate the CNS manifestations of ASMD.

Side Effects

Adverse effects associated with the use of Xenpozyme in adults may include, but are not limited to, the following:

• headache
• cough
• diarrhea
• hypotension
• ocular hyperemia

Adverse effects associated with the use of Xenpozyme in children may include, but are not limited to, the following:

• pyrexia
• cough
• diarrhea
• rhinitis
• abdominal pain
• vomiting
• headache
• urticaria
• nausea
• rash
• arthralgia
• pruritus
• fatigue
• pharyngitis

The Xenpozyme drug label comes with the following Black Box Warning: Hypersensitivity Reactions Including Anaphylaxis. Appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available. If a severe hypersensitivity reaction occurs, Xenpozyme should be discontinued immediately and appropriate medical treatment should be initiated. 

Clinical Trial Results

The FDA approval is based on positive data from the ASCEND and ASCEND-Peds clinical trials.

The ASCEND trial evaluated Xenpozyme in 31 adult patients with ASMD type A/B or type B who were randomized to receive Xenpozyme or placebo for 52 weeks. Twelve patients treated with Xenpozyme saw a 23.9% relative improvement in lung function compared to the 3% improvement in placebo comparators. Spleen and liver volume likewise dropped by 38.9% and 26.5%, respectively, after 52 weeks of Xenpozyme. Those in the placebo arm saw spleen volume increase by 0.5% and liver volume decrease by 1.8%. The most frequently reported adverse drug reactions in adults (incidence ≥10%) were headache, cough, diarrhea, hypotension, and ocular hyperemia.

The single-arm ASCEND-Peds trial studied 8 pediatric patients younger than 12 years of age with ASMD type A/B or type B who all received Xenpozyme, with a primary objective of evaluating the safety and tolerability of Xenpozyme for 64 weeks. Following one year of treatment (52 weeks), the predicted diffusing capacity of carbon monoxide (DLco) showed an average of a 33% increase in nine patients who performed the test at baseline. A 49% decrease was also observed in the spleen volumes.