No treatments are currently approved for the disease.
Paris-based Sanofi announced that its olipudase alfa had positive results in two different clinical trials for the treatment of acid sphingomyelinase deficiency (ASMD), also known as Nieman-Pick disease. Olipudase alfa is an investigational recombinant human acid sphingomyelinase.
ASMD Type A and Type B, is a rare, progressive and life-threatening disease caused by deficient activity of the enzyme acid sphingomyelinase (ASM). ASM is found in special compartments called lysosomes inside cells, which is required to break down sphingomyelin, which is a type of fat, or lipid. If sphingomyelin isn’t metabolized correctly, it accumulates inside cells, leading to cell death and major organ malfunction. It is caused by mutations in the sphingomyelin phosphodiesterase 1 gene (SMPD1). It is estimated to affect about 2,000 people in the U.S., Europe and Japan.
The U.S. Food and Drug Administration (FDA) granted olipudase alfa Breakthrough Therapy designation and the European Medicines Agency (EMA) has awarded it PRIME designation. In Japan, it was granted the SAKIGAKE designation, which is similar to both the FDA and EMA’s designations.
No treatments are currently approved for ASMD.
The Phase II/III trial investigated 36 adults with ASMD in 24 centers in 16 countries. Patients received either olipudase alfa intravenously or a placebo every two weeks at doses up to 3mg/kg over the course of a year. The trial had two independent primary efficacy endpoints that evaluated different critical manifestations, progressive lung disease and enlarged spleen, both common in ASMD. The trial was deemed positive if one of the primary endpoints was met.
The improvement in lung function endpoint was met, meaning ASCEND was considered positive. It showed a 22% relative improvement from baseline to week 52 for patients receiving olipudase alfa compared to 3% in the placebo arm.
The other primary endpoint, spleen size, was also met. In patients receiving olipudase alfa, spleen volume was decreased by 39.5% compared to 0.5% in the placebo arm.
In the U.S., spleen volume was combined with patient-reported outcome (PRO) of symptoms associated with enlarged spleen called Splenomegaly Related Score (SRS). Compared to baseline, SRS was decreased by 8.0 points in patients receiving the drug and 9.3 points in the placebo arm. This combination endpoint, then, was not met.
“These are important data in a disease with no approved treatments available currently,” said Melissa Wasserstein, chief, Division of Pediatric Genetic Medicine, Children’s Hospital at Montefiore and professor of Pediatrics and Genetics at Albert Einstein College of Medicine. Wasserstein is an investigator in the ASCEND trial.
Wasserstein added, “Treatment with olipudase alfa showed clinically meaningful improvement in pulmonary function and reduction in spleen size, critical manifestations of this progressive disease. Both of these findings are consistent across the clinical studies with olipudase alfa. The absence of an effect on SRS in this trial requires exploration, in light of the significant reduction in spleen size.”
All patients in the trial experienced at least one adverse event, although the number of events was lower in patients receiving the drug than in the placebo arm. Severe adverse events were less common in the olipudase alfa arm, only three events, compared to 13 in the placebo arm. The most common adverse events were headache, nasopharyngitis, upper respiratory tract infection, cough, and arthralgia.
Sanofi plans to present the data at future medical meetings and begin global regulatory submissions in the second half of 2021.
