5PSQ-007 Sebelipase alfa as enzyme replacement therapy in three paediatric patients

Background Lysosomal acid lipase deficiency (LALD) is a rare lysosomal disorder characterised by clinical with dyslipidaemia and steatohepatitis. Sebelipase-alfa is a recombinant human LAL, recently approved for clinical use in LALD. Purpose Evaluation of the effectiveness and safety of sebelipase-alfa as enzyme replacement therapy in paediatric patients with LALD. Material and methods Observational, retrospective study included three patients treated with sebelipase-alfa. From clinical history the following data were obtained: age, sex, diagnosis, values of total cholesterol, low-density lipoprotein (LDL), high density lipoprotein (HDL), triglycerides (TG), alanine- aminotransferase (ALT) and aspartate aminotransferase (AST), liver size and fibrosis before and during treatment with sebelipase alfa, and adverse events. From the outpatient programme were obtained dose, administrations and weeks of treatment. The efficacy was evaluated by normalising the analytical values of the lipidic and liver profiles in three patients who participated in the clinical trial until April 2018. Results Three male brothers 12, 15 and 17 years’ old diagnosed with LALD before 5 years, heterozygous for mutation in the LIPA gene c.894G>A, c.256C>T. Before the trial, patients presented abnormal analytical values (except TG), hepatomegaly and fibrosis. Patients received continuous treatment with sebelipase-alfa at a dose of 1 mg/kg/2 weeks intravenously. Preparation of the medication was carried out by the hospital pharmacy service. In April 2018, after 225, 183 and 114 weeks of treatment respectively, all three patients maintained the values analysed in the range of normality (except HDL in two and TG in one patient). Hepatomegaly reversed in all patients. The means of the values and of the percentages of variation to the basal were: cholesterol 150.66±22.89 mg/dL (−34.19%), LDL 89.33±12.20 mg/dL (−46.90%), HDL 35.66±6.35 mg/dL (+1.55%), AST 30.66±4.04 IU/L (−64.88%), ALT 21.33±4.93 mg/dL (−65.99%) and TG 130±85.91 mg/dL (+2.12%). Concerning safety, two patients who suffered diarrhoea, and adverse effects related to the infusion were not reported. Conclusion LALD is a rare disease, and sebelipase-alfa is the first drug authorised for its treatment. The response to treatment with sebelipase-alfa has been favourable from the beginning, with an improvement in the studied variables and a good safety profile in the reported cases. References and/or acknowledgements Pharmacy Hospital La Paz. No conflict of interest.