6533b836fe1ef96bd12a099d
RESEARCH PRODUCT
A Phase 3 Trial of Sebelipase Alfa in Lysosomal Acid Lipase Deficiency
Manisha BalwaniEugen MengelYijun YangHeidi PetersVratislav SmolkaVassili ValayannopoulosBarbara K. BurtonGregory M. EnnsAnthony G. QuinnChristina M. LaukaitisMaurizio ScarpaIvo BarićFatih Süheyl EzgüSandra Rojas-caroKatryn N. FuruyaStephen EckertZachary GoodmanFrançois FeilletJohn P. KaneRichard W. ErbeT. Andrew BurrowK Otfried SchwabAlejandra Consuelo-sanchezCan FiciciogluScott NightingaleEdward G. NeilanPatrick DeeganCarmen Camarena GrandeMarnie WoodMaja Di RoccoMahmut ÇOkersubject
AdultMalemedicine.medical_specialtyCirrhosisAdolescentHDLBiopsy[SDV]Life Sciences [q-bio]Lysosomal acid lipase deficiencyGastroenterologyLDLlaw.inventionYoung Adultchemistry.chemical_compoundDouble-Blind MethodRandomized controlled triallawInternal medicinemedicineHumansAdolescent; Adult; Aged; Alanine Transaminase; Biopsy; Child; Child Preschool; Cholesterol HDL; Cholesterol LDL; Double-Blind Method; Dyslipidemias; Female; Humans; Liver; Male; Middle Aged; Sterol Esterase; Wolman Disease; Young AdultChildPreschoolComputingMilieux_MISCELLANEOUSAgedDyslipidemiasbiologyCholesterolbusiness.industryWolman DiseaseAlanine TransaminaseLipid metabolismGeneral MedicineMiddle AgedSterol Esterasemedicine.disease3. Good healthCholesterolEndocrinologyLiverSebelipase alfachemistryAlanine transaminasebiology.proteinFemalebusinessDyslipidemiadescription
BackgroundLysosomal acid lipase is an essential lipid-metabolizing enzyme that breaks down endocytosed lipid particles and regulates lipid metabolism. We conducted a phase 3 trial of enzyme-replacement therapy in children and adults with lysosomal acid lipase deficiency, an underappreciated cause of cirrhosis and severe dyslipidemia. MethodsIn this multicenter, randomized, double-blind, placebo-controlled study involving 66 patients, we evaluated the safety and effectiveness of enzyme-replacement therapy with sebelipase alfa (administered intravenously at a dose of 1 mg per kilogram of body weight every other week); the placebo-controlled phase of the study was 20 weeks long and was followed by open-label treatment for all patients. The primary end point was normalization of the alanine aminotransferase level. Secondary end points included additional disease-related efficacy assessments, safety, and side-effect profile. ResultsSubstantial disease burden at baseline included a very high level of low-densit...
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-09-10 |