FDA OKs First Treatment for Acid Sphingomyelinase Deficiency

The first disease-specific treatment for acid sphingomyelinase deficiency (ASMD) gained FDA approval on Wednesday, the agency announced.

Olipudase alfa (Xenpozyme) is an IV infusion indicated for treating non-central nervous system manifestations in pediatric and adult patients with ASMD type A/B or type B.

The rare genetic disease is caused by a lack of an enzyme to break down the lipid sphingomyelin and often leads to premature death. Olipudase alfa acts as an enzyme replacement therapy to reduce sphingomyelin accumulation in the liver, spleen, and lung.

Most patients with ASMD, historically known as Niemann-Pick disease, experience enlarged abdomens that result in pain, vomiting, feeding difficulties, and falls. The most severe cases typically manifest in neurologic symptoms, leading to death by the age of 3 years. Those who survive into adulthood then often die from respiratory failure.

"ASMD has a debilitating effect on people's lives and there is a critical need to increase treatment options for patients who suffer from this rare disease," said Christine Nguyen, MD, deputy director of the FDA Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine, in a statement. "The challenges involved with developing treatments for rare diseases are significant and unique. We believe patients who suffer from ASMD, their families and their physicians will welcome this long-awaited advancement."

Approval was based on the ASCEND and ASCEND-Peds trials conducted by Genzyme/Sanofi.

In ASCEND, which involved 31 adult patients with ASMD type A/B or type B, those on olipudase alfa saw a greater improvement in lung function -- measured as predicted diffusing capacity of the lung for carbon monoxide -- by week 52 of treatment compared to those on placebo (24% vs 3% relative improvement over baseline).

In ASCEND-Peds, which involved eight pediatric patients with ASMD type A/B or type B, lung function improved by a relative 45.9% from baseline in three assessable patients, according to a release from Sanofi.

Treatment with olipudase alfa also reduced liver and spleen size. Olipudase alfa has not been studied in ASMD type A.

The most common side effects included headache, cough, fever, joint pain, diarrhea, and low blood pressure. In the trials, 75% of pediatric patients and 50% of adult patients experienced reactions including headaches, nausea, and vomiting while receiving IV infusion.

The treatment is administered intravenously every 2 weeks, with a dose escalation phase followed by a maintenance phase.

The agent's label carries a boxed warning regarding severe hypersensitivity reactions that can include anaphylaxis. Routine blood tests are recommended while on treatment, as some patients may develop abnormalities, like abnormal liver blood tests.

Pregnant women should avoid treatment, as animal studies demonstrated possible fetal harm.

Olipudase alfa is expected to hit U.S. shelves in the next few weeks with a list price of $7,142.00 per vial.

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