On Aug. 31, 2022, the United States Food and Drug Administration (FDA) granted approval to Sanofi for the first medication indicated to treat non-central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in adult and pediatric individuals. Xenpozyme™ (olipudase alfa-rpcp) is an enzyme replacement therapy given as an intravenous (IV) infusion titrated up every two weeks until a recommended maintenance dose of 3mg/kg once every two weeks regardless of the patient’s age is achieved. The starting dose is 0.1mg/kg in adult patients and 0.03mg/kg in pediatric patients. Acid sphingomyelinase deficiency (ASMD) is a rare progressive genetic lysosomal storage disorder that results from a deficiency of the enzyme acid sphingomyelinase, which is required to break down a fatty substance called sphingomyelin. In patients with ASMD, sphingomyelin and other substances accumulate in various tissues of the body. Sanofi is listing the wholesale acquisition cost (WAC) at $7,142 per vial. It will be dispensed through a large network of specialty pharmacies that includes Accredo. For full prescribing information see here.

At a Glance

• Brand (Generic) Name: Xenpozyme (olipudase alfa-rpcp)
• Manufacturer: Sanofi
• Date Approved: Aug. 31, 2022
• Indication: For the treatment of non-central nervous system (non-CNS) manifestations of acid sphingomyelinase deficiency (ASMD) in adult and pediatric patients
• Dosage Forms Available: Single-dose vial containing 20mg of olipudase alfa-rpcp lyophilized for reconstitution and IV infusion
• Launch Date: In the coming weeks
• Estimated Annual Cost: Wholesale acquisition cost (WAC) is $7,142 per vial or approximately $780,000 per year, which is estimated to be the median annual cost. This represents the estimated annual cost for a 50-pound child. It will cost over $1 million per year for an adult.
• ASMD, which is caused by mutations in the SMPD1 gene, affects approximately one in 250,000 individuals with an estimated 120 patients diagnosed with ASMD in the U.S. The gene is required to produce an enzyme needed to break down sphingomyelin, a fat that accumulates in organs of the body including the liver, spleen, lungs, and brain.
• Patients who have ASMD may have enlarged spleens or livers with symptoms of jaundice, ascites, constipation, nausea, vomiting, feeding problems, gastrointestinal reflux, irritability, loss of reflexes, dyslipidemia, progressive loss of muscle tone and bone density.
• Enlargement of the liver and spleen can lead to low levels of platelets, and white blood cells (WBCs) which puts individuals at risk for infection or bleeding episodes.
• Sphingomyelin accumulation in the lungs also can result in reoccurring respiratory infections, difficulty breathing or respiratory failure.
• The disease is highly variable. If untreated, the most severe form, Niemann-Pick disease (NPD) type A, is a neurodegenerative disorder that limits patient life to about three years of age. NPD type B is milder, with limited neurologic symptoms that allow some individuals who have it to survive into adulthood. NPD type A/B is an in-between form of the disease that has varying degrees of neurological involvement.
• No other treatments are FDA approved for ASMD. However, patients often undergo physical and occupational therapy, as well as nutrition support. Blood transfusions may be required for prolonged bleeding episodes. Patients with lung disease could require oxygen therapy. Liver transplants are sometimes required in patients who have liver failure.
• Xenpozyme was approved based on a double-blind, randomized, placebo-controlled study in 31 patients who have ASMD type A/B or type B. They were randomized to receive either active treatment or placebo for 52 weeks. Lung function was observed as a measure of the percent change from baseline as predicted from the lungs ability to diffuse carbon monoxide (DLco). Patients treated with Xenpozyme had a 23.9% improvement in DLco vs. a 3% improvement for patients treated with placebo. Xenpozyme was also effective in reducing liver and spleen volumes in treated patients.
• Xenpozyme has a boxed warning for hypersensitivity reactions including anaphylaxis. The most frequent adverse events included headache, cough, diarrhea, eye redness and hypotension.
• Xenpozyme was approved with Breakthrough Therapy, Priority Review, Fast Track and Orphan Drug Designation. The company was also awarded a Rare Pediatric Disease Priority Review voucher that can be used for future FDA submissions or sold to another company.