Sanofi Wins Japanese Approval for First Treatment for Niemann-Pick Disease

Rare Daily Staff

The Japanese Ministry of Health, Labor, and Welfare has granted marketing authorization for Sanofi’s Xenpozyme for the treatment of adult and pediatric patients with non-central nervous system manifestations of acid sphingomyelinase deficiency (ASMD), a rare, progressive, and potentially life-threatening genetic disease.

Historically known as Niemann-Pick disease types A, A/B, and B, ASMD is an autosomal recessive lysosomal storage disorder that stems from mutations in the gene that encodes for sphingomyelinase. In the absence of normal levels of the enzyme, a lipid called sphingomyelin accumulates in cells, causing cell death and organ malfunction.

ASMD represents a spectrum of disease, with two types that may represent opposite ends of a continuum referred to as ASMD type A and ASMD type B. ASMD type A/B is an intermediate form that includes varying degrees of CNS involvement.

Xenpozyme (olipudase alfa) is currently the only approved treatment for ASMD and represents Sanofi’s first therapy to be approved under the SAKIGAKE (or “pioneer”) designation, which is the Japanese government’s regulatory fast-track pathway to promote research and development of innovative new medical products addressing urgent unmet medical needs.

“Today’s approval of Xenpozyme is a watershed moment for ASMD patients and their families, representing 20 years of research and the shared efforts of advocacy partners, clinicians, and patients. As the world’s first medicine approved for ASMD, Xenpozyme offers a potentially transformative option for this historically neglected community,” said John Reed, executive vice president and global head of Research and Development, Sanofi. 

Xenpozyme is a recombinant human acid sphingomyelinase enzyme developed to replace deficient or defective acid sphingomyelinase (ASM), an enzyme that allows for the breakdown of the lipid sphingomyelin. Accumulation of sphingomyelin in cells can cause harm to the lungs, spleen, and liver, as well as other organs, potentially leading to early death.

The approval of Xenpozyme in Japan is based on positive results from the ASCEND and ASCEND-Peds clinical trials, showing that Xenpozyme provided improvement in lung function (as measured by diffusing capacity of the lung for carbon monoxide, or DLco) and reduction of spleen and liver volumes, with a well-tolerated safety profile in adults and children with ASMD. These data were presented at the American Society of Human Genetics 2020 Virtual Meeting.

Xenpozyme has been evaluated in children and adults to treat non-CNS manifestations of ASMD type A/B and ASMD type B. Xenpozyme has not been studied in patients with ASMD type A.

Outside of Japan, olipudase alfa is being evaluated by regulatory authorities around the world. A Biologics License Application (BLA) for olipudase alfa was accepted for Priority Review by the U.S. Food and Drug Administration, with a decision expected in the second half of 2022. The European Medicines Agency (EMA) has awarded olipudase alfa the PRIority MEdicines (PRIME) designation, and a decision is also anticipated in the second half of 2022.

Photo: John Reed, executive vice president and global head of Research and Development, Sanofi.