In the past, there has never been an approved therapeutic option for those with acid sphingomyelinase deficiency (ASMD). This meant that there was a huge unmet need within this patient population. However, this has recently changed. On March 28, 2022, global healthcare company Sanofi shared via the Associated Press that its therapeutic option Xenpozyme (olipudase alfa) was approved in Japan. This is now the first – and only – approved treatment option for ASMD.

Xenpozyme: An Overview

Developed by Sanofi, Xenpozyme (olipudase alfa) is an enzyme replacement therapy (ERT) designed to replace defective or missing acid sphingomyelinase (ASM) in the body. Normally, ASM helps to break down sphingomyelin, a type of lipid. But those with ASMD have SMPD1 gene mutations which either prevent the production of ASM or cause it to be defective. Therefore, sphingomyelin accumulates in cells, causing damage to organs like the liver, lungs, and spleen.

The drug was approved in Japan for the treatment of ASMD types A/B and B. It is not yet approved for another subtype, which is type A; this has not yet been studied in trials. Altogether, the approval hinged on data from the ASCEND and ASCEND-Peds studies. The data highlighted the therapy’s ability to reduce enlarged livers and spleens, as well as improve lung function. Xenpozyme was also found to be safe and well-tolerated.

Japan approved Xenpozyme for both adults and children with ASMD under the SAKIGAKE (“pioneer”) designation. Outside of Japan, Xenpozyme has also received PRIME designation in the EU, as well as Breakthrough Therapy designation in the United States.

What is Acid Sphingomyelinase Deficiency (ASMD)?

Also known as Niemann-Pick disease type A and Type B, acid sphingomyelinase deficiency (ASMD) is a rare and progressive genetic lysosomal storage disorder. It is inherited in an autosomal recessive pattern, meaning patients must inherit one defective gene from each parent. ASMD is typically very variable. For those with the more severe infantile neurovisceral form, patients may die in early childhood. In others with more mild forms, it is possible to live into adulthood. ASMD type A is more common in those of Ashkenazi Jewish heritage.

Symptoms associated with AMSD can include:

• Irritability
• Enlarged liver and spleen
• Failure to thrive
• Abdominal ascites
• Jaundice (yellowing of the skin, eyes, and mucous membranes)
• Cherry red spots on the macula
• Osteopenia
• Feeding difficulties
• Gastrointestinal reflux
• Loss of muscle tone
• Nausea and vomiting
• Constipation
• Frequent or recurrent respiratory infections and/or difficulty breathing
• Progressive neurological deterioration
• Neutropenia and thrombocytopenia (lowered platelets and white bloodcell counts)