Plain Language Summary of the ASCEND study looking at the results of treatment with olipudase alfa after one year in adults with acid sphingomyelinase deficiency (ASMD)

What is acid sphingomyelinase deficiency (ASMD)?: ASMD is a rare genetic condition. People with ASMD do not make enough of a fully working enzyme called acid sphingomyelinase. This means a fatty substance called sphingomyelin cannot be broken down and builds up in the lungs, liver and spleen, leading to poor health. An enzyme replacement treatment called olipudase alfa is a fully working acid sphingomyelinase enzyme that helps break down sphingomyelin in the body so organs can work properly. What is this study about?: The ASCEND study looked at how well treatment with olipudase alfa worked in adults with ASMD, compared with placebo (a treatment that looked like olipudase alfa but contained no medicine). The researchers looked at how well the lungs, liver and spleen worked and the side effects of treatment. What were the results of the study?: The ASCEND study showed that in adults with ASMD, compared to placebo, olipudase alfa: ○ Decreased liver and spleen size. ○ Improved lung function.▪ Increased the amount of gas that the lungs can take from inhaled air into the bloodstream.▪ Improved scores from lung images (lowered the build-up of sphingomyelin in the lungs).○ Improved liver function.▪ Lowered the amount of sphingomyelin in the liver, showing that olipudase alfa broke down sphingomyelin.▪ Lowered amounts of liver enzymes in the blood, which signals there is less damage to liver cells.▪ Improved levels of lipids (good and bad cholesterol) and increased the levels of platelets, which are a type of specialized blood cell that forms clots to slow and stop bleeding. Most side effects from treatment with olipudase alfa were mild and no-one stopped treatment due to any side effects. The most common side effect from treatment with olipudase alfa or the infusion was headache. What do the results of the study mean?: The ASCEND study showed that olipudase alfa reversed sphingomyelin build-up and stopped the disease getting worse in the liver, spleen and lungs. This could decrease the impact the disease has on people with ASMD and improve their health. There were no major safety concerns from treatment with olipudase alfa. Clinical Trial Registration:NCT02004691 ASCEND study (ClinicalTrials.gov).