FDA Approves Xenpozyme for ASMD, a Rare Genetic Disorder

Xenpozyme, the first disease-specific treatment for acid sphingomyelinase deficiency (ASMD), is expected to be available in the United States in the coming weeks at a wholesale acquisition cost of $7,142 per vial.

The FDA has approved Sanofi’s Xenpozyme (olipudase alfa-rpcp) to treat both adults and children with acid sphingomyelinase deficiency (ASMD). Xenpozyme is an intravenous infusion used for the treatment of non-central nervous system (non-CNS) manifestations of the disease.

ASMD, historically known as Niemann-Pick disease types A, A/B, and B, is a rare genetic disorder where a deficiency of the enzyme acid sphingomyelinase results in sphingomyelin accumulating in various tissues in the body. Patients with ASMD have enlarged abdomens that can cause pain, vomiting, feeding difficulties, and falls. The most severely affected patients have profound neurologic symptoms and rarely survive beyond two to three years of age. Other patients may survive into adulthood but die prematurely from respiratory failure. It has been estimated that there are fewer than 120 patients diagnosed with ASMD in the United States. About two-thirds of patients with ASMD in the United States are children.

Xenpozyme is designed to replace deficient or defective acid sphingomyelinase (ASM). Xenpozyme is not expected to cross the blood-brain barrier or modulate CNS manifestations of ASMD. The therapy has not been studied in patients with ASMD type A.

Xenpozyme is expected to be available in the United States in the coming weeks. The wholesale acquisition cost of Xenpozyme of $7,142 per vial, according to Sanofi.

“ASMD is an extremely rare, progressive, and potentially fatal genetic disease that impacts children and adults around the world,” Melissa Wasserstein, M.D., Pediatric Genetic Medicine, Albert Einstein College of Medicine and the Children’s Hospital at Montefiore, said in a press release. “Until now, those living with ASMD have had no FDA-approved treatment to combat this devastating condition.”

The approval is based on positive data from the ASCEND and ASCEND-Peds clinical trials, in which Xenpozyme showed clinically relevant improvement in lung function and platelet count, and reduction of spleen and liver volumes. The ASCEND trial evaluated Xenpozyme in 31 adult patients. Twelve patients treated with Xenpozyme had a mean change in percent predicted carbon monoxide from baseline (49.1%) to week 52 (59.4%). Thirteen patients treated with Xenpozyme had a mean improvement in platelet count by 18.3% from baseline to week 52 compared with increase by 2.7% for the 16 patients in the placebo group.

The single-arm ASCEND-Peds trial studied 8 pediatric patients younger than 12 years of age with ASMD type A/B or type B. Three patients who were able to perform the test at baseline treated with Xenpozyme had a mean relative improvement of 45.9% in percent predicted carbon monoxide from baseline (48.5%) to week 52 (70.9%). Seven patients treated with Xenpozyme had a mean improvement in platelet count by 37.6% from baseline to week 52.

The most common side effects of Xenpozyme include headache, cough, fever, joint pain, diarrhea, and low blood pressure. Xenpozyme carries a boxed warning for severe hypersensitivity reactions including anaphylaxis.