Volumen: 17 # Number : Número Extraordinario
Publication Date : Agosto Year: 2013
Authors: Dragosky M; Bolesina M ; Jozami C; Watman N
Abstract: In Gaucher Disease type 1(GD1), deficient acid beta glucosidase activity causes accumulation of glucosylceramide (GL-1). Eliglustat, a novel, potent
and specific glucosylceramide synthase inhibitor,
is under development as an oral substrate
reduction therapy for GD1. This phase 2 study enrolled 26 adult patients who were not receiving GD1-specific treatment in the prior 12 months, 19 of them completed 3 years. Efficacy outcomes included
changes in hemoglobin and platelet levels, spleen and liver volumes and bone mineral density
(BMD). Achievement of therapeutic goals was measured. After three years of treatment with eliglustat,
mean hemoglobin level and platelet count increased by 2.6g/dl and 91 %, respectively, mean spleen and liver volume by 61 % and 29 % respectively
(all P<0001). The majority of patients met long-term therapeutic goals. Mean lumbar spine BMD increased by 0.6 z-score; femur dark marrow was reduced or stable. There were no bone crisis, new lytic lesions or bone infarcts, or worsening of preexisting lytic lesions or infarcts. Eliglustat was well tolerated. The majority of adverse events (AEs) observed during three years were mild (74%) and unrelated to treatment (95%). Eight drug-related AEs, all mild, occurred in 6 patients.
Conclusions: Eligustat has shown promising efficacy
and safety, with clinical improvements in hematologic,
visceral and bone parameters.
Key words: Gaucher Disease Type 1, Substrate Reduction
Therapy, eliglustat
Pages : 17-24
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