One-year results of the placebo-controlled ASCEND trial of olipudase alfa enzyme replacement therapy in adults with chronic acid sphingomyelinase deficiency

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... Two separate clinical studies evaluating olipudase alfa for the treatment of chronic ASMD in adult and paediatric patients have also demonstrated positive results [27,31]. The Phase I/II open label, ascending dose, multicentre ASCEND-Peds study (NCT02292654) evaluated the safety, tolerability, and pharmacokinetics of olipudase alfa in 20 paediatric patients with chronic visceral ASMD over a 64-week study period [27]. ...
... Most AEs were mild to moderate in severity, and no permanent treatment discontinuations were reported. The ongoing Phase II/III randomised, double-blind, placebo-controlled ASCEND (adults) study (NCT02004691) evaluated the efficacy, safety, and pharmacokinetics/pharmacodynamics of olipudase alfa in 36 adults with chronic visceral ASMD over a 52-week primary analysis period, which is now being followed by an extension period (all treated patients) of up to 4 years [31]. Patients received either olipudase alfa intravenous infusion or placebo every two weeks at an escalating dose from 0.1 mg/kg up to 3 mg/kg administered every two weeks. ...
... Similarly, in 2016, olipudase alfa has gained orphan designation and 'PRIority Medicines' (PRIME) designation by the European Medicines Agency, along with being awarded the SAKIGAKE designation in Japan, in order to expedite the regulatory process [33]. [31]. The aim of the dose-escalation process of olipudase alfa is gradual sphingomyelin debulking to prevent high ceramide release. ...
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Acid sphingomyelinase deficiency (ASMD) is a rare inherited lipid storage disorder caused by a deficiency in lysosomal enzyme acid sphingomyelinase which results in the accumulation of sphingomyelin, predominantly within cells of the reticuloendothelial system located in numerous organs, such as the liver, spleen, lungs, and central nervous system. Although all patients with ASMD share the same basic metabolic defect, a wide spectrum of clinical presentations and outcomes are observed, contributing to treatment challenges. While infantile neurovisceral ASMD (also known as Niemann–Pick disease type A) is rapidly progressive and fatal in early childhood, and the more slowly progressive chronic neurovisceral (type A/B) and chronic visceral (type B) forms have varying clinical phenotypes and life expectancy. The prognosis of visceral ASMD is mainly determined by the association of hepatosplenomegaly with secondary thrombocytopenia and lung disease. Early diagnosis and appropriate management are essential to reduce the risk of complications and mortality. The accessibility of the new enzyme replacement therapy olipudase alfa, a recombinant human ASM, has been expedited for clinical use based on positive clinical data in children and adult patients, such as improved respiratory status and reduced spleen volume. The aim of this article is to share the authors experience on monitoring ASMD patients and stratifying the severity of the disease to aid in care decisions.
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