Sanofi rare disease med clinches world-first nod in Japan, presaging potential approvals in US, Europe

The world’s first therapy for rare disease Niemann-Pick types A/B and B has surfaced in Japan, courtesy of Sanofi. With one global approval down, Sanofi hopes to score nods for the drug in the U.S. and Europe before the year is out.

Japan’s drug regulator has cleared Sanofi’s Xenpozyme, also known as olipudase alfa, to treat kids and adults with non-central nervous system (non-CNS) manifestations of acid sphingomyelinase deficiency (ASMD), the company said Monday.

Xenpozyme now holds the distinction of being the “only approved treatment for ASMD,” Sanofi noted in a release. Regulators approved the drug under Japan’s Sakigake fast-track designation. Meanwhile, Xenpozyme is up for priority review in the U.S., where Sanofi expects a decision early in the third quarter, and it boasts Priority Medicines (PRIME) status in the EU, where regulators aim to reach a verdict in the second half of 2022.

Historically known as Niemann-Pick disease types A, A/B and B, ASMD is a genetic, progressive, and potentially fatal disease, Sanofi pointed out. The autosomal recessive lysosomal storage disorder 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.

“Until now, no approved therapies for ASMD have been available anywhere in the world,” Sanofi said in its approval announcement.

Sanofi has estimated the disease affects around 2,000 people in U.S., Europe and Japan, with around 3% of people with the disease dying annually because of respiratory or liver failure.

Xenpozyme is a recombinant human acid sphingomyelinase (ASM) enzyme designed to replace deficient or defective ASM, Sanofi explained. It's specifically approved in Japan to treat ASMD types A/B and B, and it hasn’t been studied in ASMD type A, Sanofi said.

The approval marks a “watershed moment” for the ASMD community, capping off two decades of research and the combined efforts of advocates, doctors and patients, John Reed, M.D., Ph.D., Sanofi's global head of research and development, said in a statement. “As the world’s first medicine approved for ASMD, Xenpozyme offers a potentially transformative option for this historically neglected community.”

Japan’s Ministry of Health, Labor and Welfare based its decision on results from Sanofi’s ASCEND and ASCEND-Peds studies, which showed Xenpozyme helped improve lung function and reduce spleen and liver volumes.

In the 36-subject phase 2/3 ASCEND trial in adults, patients who received biweekly infusions of Xenpozyme for a year experienced 22% improvement from baseline in a measure of lung function versus 3% in the placebo arm, Sanofi revealed in early 2020. Meanwhile, the spleen volumes of patients on Xenpozyme fell by 39.5% over the trial’s run versus an increase of 0.5% in the control cohort.

Further, the phase 2 ASCEND-Peds study weighed Xenpozyme’s safety and tolerability in kids. Results from that study were slightly muddier, with three patients experiencing five treatment-related serious adverse events between them—though none of those reactions led to a patient permanently discontinuing participation in the trial, Sanofi noted in 2020.

With Xenpozyme’s inaugural approval in the books, Sanofi’s next goal is to “rush this important medicine to ASMD patients around the world,” Reed added.