Sanofi’s Enzyme Replacement Therapy Xenpozyme Wins FDA Approval for Rare Disease ASMD

After approvals in Japan and Europe, Sanofi’s Xenpozyme has secured one from the US Food and Drug Administration (FDA) 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 genetic lysosomal storage disease caused by mutations in the sphingomyelin phophodiesterase-1 (SMPD1) gene that codes for the acid sphingomyelinase (ASM) enzyme. ASM is required for breaking down a complex lipid called sphingomyelin. Due to the enzyme deficiency, the lipid accumulates in the liver, spleen, lung and brain, causing symptoms including an enlarged abdomen that can result in pain, vomiting, feeding difficulties and falls.

Lysosomal storage diseases are rare inherited disorders characterized by metabolic deficiencies resulting in the toxic buildup of materials that can’t be broken down by the body.

In severe cases of the rare progressive disorder, historically known as Niemann-Pick disease types A, A/B and B, patients have significant neurologic symptoms and rarely survive beyond two to three years of age. Other patients may survive into adulthood but die prematurely from respiratory failure.

Xenpozyme is a hydrolytic lysosomal sphingomyelin-specific enzyme replacement therapy that replaces deficient or defective ASM enzyme to help reduce the accumulation of sphingomyelin in vital body organs.

According to Sanofi, of the less than 120 people diagnosed with ASMD in the US, about two-thirds are children.

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Sanofi picked up its first Xenpozyme approval for the treatment of Niemann-Pick from Japanese regulators in March followed by an approval from European officials in May.

Xenpozyme is administered intravenously every two weeks, with a dose escalation phase followed by a maintenance phase.

In a press release, Sanofi said Xenpozyme is not expected to cross the blood-brain barrier nor impact CNS manifestations of ASMD.

The FDA approval was based on data from the randomized, double-blind, placebo-controlled ASCEND study involving 31 adult patients. Patients in the trial received Xenpozyme or placebo for 52 weeks. Treatment with Xenpozyme improved lung function and also reduced liver and spleen size.

The treatment was also evaluated in the pediatric arm of the study, ASCEND-peds, which included eight pediatric patients younger than 12 years of age with ASMD who all received Xenpozyme. The pediatric patients showed improvements similar to the adults patients with respect to lung function and reductions in liver and spleen sizes.

In the trials, 75 percent of pediatric patients and 50 percent of adult patients experienced adverse reactions while receiving Xenpozyme that included headaches, nausea and vomiting.

Sanofi said Xenpozyme is expected to be available in the US in the coming weeks with a list price of $7,142 per vial. The company said, “actual patient out-of-pocket costs may be lower, as the list price does not reflect insurance coverage, co-pay support for eligible patients, or financial assistance from patient support programs.”

In its commitment to improving treatment access and affordability of innovative therapies, the company said it provides disease education, financial and co-pay assistance programs, and other support services to eligible patients.

The FDA approval came ahead of its October 3 target date, which had been extended by three months.

The FDA granted Xenpozyme fast track, breakthrough therapy, orphan drug and priority review designations. The FDA also awarded the sponsor (Genzyme, acquired by Sanofi in 2011) a rare pediatric disease priority review voucher, an incentive to encourage development of new drugs and biologics for the prevention and treatment of rare diseases in children, according to the FDA.

The FDA says more than 7,000 rare diseases affect more than 30 million people in the US, and estimates that half of the most serious and life-threatening diseases affect children.

In addition to Xenpozyme, Sanofi garnered approval for another enzyme replacement therapy, Nexviadyme, in Europe this year as the first new treatment option for Pompe disease approved in Europe in more than 15 years.