Sanofi has revealed positive topline results for its rare disease candidate olipudase alfa, a potentially first-in-class treatment for acid sphingomyelinase deficiency (ASMD).
The FDA has already awarded the drug a coveted breakthrough status, which fast-tracks the development of any treatment for a serious or life-threatening condition.
Olipudase alfa is designed to replace the enzyme that is deficient in the inherited disease, also known as Neimann-Pick disease. The enzyme deficiency causes harmful quantities of a fatty substance called sphinogomyelin to build up in the body’s organs.
Sanofi is developing olipudase alfa for the type B variant of the disease, in which the build-up occurs mainly in the liver, spleen and lungs.
The drug is not yet being developed in the type A form of ASMD, in which sphingomyelin accumulation takes place mainly in the central nervous system.
ASMD is in a class of around 50 diseases known as lysosomal storage disorders (LSDs), a group which also includes Gaucher and Fabry disease.
Sanofi tested the drug in adults patients and paediatric patients with ASMD – ASCEND and ASCEND-Peds.
In the ASCEND trial of 36 adults with ASMD, the drug met its primary endpoint of improvement in lung function, with the relative improvement from baseline to week 52 at 22% for the olipudase alfa arm compared to 3% in the placebo arm.
The drug also met another primary endpoint of reducing spleen size, as assessed from baseline in multiples of normal spleen volume. In the olipudase alfa arm, the spleen volume reduced by 39.5% compared with a 0.5% increase in the placebo arm.
In the paediatric trial, the study showed that, although all patients experienced at least one adverse effect with olipudase alfa treatment, lung function improved and spleen volume decreased.
Sanofi has said it will submit the results from these trials to future medical meetings, and that they will also form the basis of regulatory submissions expected to begin in the second half of 2021.
“These are important data in a disease with no approved treatments available currently,” said Melissa Wasserstein, chief, Division of Paediatric Genetic Medicine, Children's Hospital at Montefiore; Professor of Paediatrics and Genetics, Albert Einstein College of Medicine; and an investigator in the ASCEND trial.
“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,” she added.
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