The Food and Drug Administration (FDA) has approved Xenpozyme (olipudase alfa-rpcp) for the treatment of non-central nervous system (non-CNS) manifestations of acid sphingomyelinase deficiency (ASMD) in adult and pediatric patients.

ASMD is a rare progressive genetic disease characterized by a deficiency of the enzyme acid sphingomyelinase, which results in the accumulation of sphingomyelin in various tissues of the body. Xenpozyme is a hydrolytic lysosomal sphingomyelin-specific enzyme replacement therapy designed to replace deficient or defective ASM. It has not been studied in patients with ASMD type A.

The approval of Xenpozyme was based on efficacy and safety data from the phase 2/3 ASCEND ( Identifier: NCT02004691) and phase 1/2 ASCEND-Peds ( Identifier: NCT02292654) trials. The ASCEND trial included 31 adults with ASMD type A/B or type B who were randomly assigned to receive Xenpozyme or placebo for 52 weeks. The major efficacy endpoints included assessment of % predicted diffusing capacity of the lung for carbon monoxide (DLco), spleen volume, liver volume and platelet count.

Continue Reading

At week 52, results showed an increase of 20.9% ([95% CI, 10.6-31.2]; P =.0003) in the mean percent change in % predicted DLco in Xenpozyme-treated patients compared with patients who received placebo. Patients in the Xenpozyme arm also had a mean reduction in spleen volume of 39.4% ([95% CI, -47.6, -31.2]; P <.0001) compared with the placebo group. A decrease in mean liver volume (-24.7% [95% CI, -33.4, -16.1]; P <.0001) and an increase in mean platelet count (15.6% [95% CI, 1.8-29.4]; P =.0280) were noted in the Xenpozyme-treated patients compared with the placebo group.

In the single-arm ASCEND-Peds trial, 8 patients less than 12 years of age with ASMD type A/B or type B received Xenpozyme for 64 weeks. At 52 weeks, patients achieved improvements in mean percent change in % predicted DLco, spleen and liver volumes, platelet counts, and linear growth progression (as measured by height Z-scores).

As for safety, Xenpozyme carries a Boxed Warning associated with a risk for severe hypersensitivity reactions including anaphylaxis. The most commonly reported adverse events in adults were headache, cough, diarrhea, hypotension, and ocular hyperemia. In pediatric patients, the most commonly reported adverse events were pyrexia, cough, diarrhea, rhinitis, abdominal pain, vomiting, headache, urticaria, nausea, rash, arthralgia, pruritus, fatigue, and pharyngitis.

Xenpozyme is supplied as a single-dose vial containing 20mg of olipudase alfa-rpcp as a lyophilized powder for reconstitution. The product is expected to be available in the coming weeks. Commenting on the approval, Christine Nguyen, MD, deputy director of the Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine in the FDA’s Center for Drug Evaluation and Research, said: “We believe patients who suffer from ASMD, their families and their physicians will welcome this long-awaited advancement.”


  1. FDA approves first treatment for acid sphingomyelinase deficiency, a rare genetic disease. News release. US Food and Drug Administration. Accessed August 31, 2022.
  2. Press Release: Xenpozyme (olipudase alfa-rpcp) approved by FDA as first disease-specific treatment for ASMD (non-CNS manifestations). News release. Sanofi – Aventis Groupe. Accessed August 31, 2022.
  3. Xenpozyme. Package insert. Sanofi – Aventis Groupe; 2022. Accessed August 31, 2022.

This article originally appeared on MPR