title: Improvement in hematological, visceral, and skeletal manifestations of Gaucher disease type 1 with oral eliglustat tartrate (Genz-112638) treatment: 2-year results of a phase 2 study.
abstract: Eliglustat tartrate is an investigational oral substrate reduction therapy for Gaucher disease type 1 that is pharmacologically distinct from intravenous enzyme replacement therapy. Eliglustat tartrate improved clinical manifestations in patients who received 50 or 100 mg twice daily for 1 year during an open-label phase 2 study (Blood. 2010;116(6):893-899). We report further improvements after 2 years of treatment in 20 patients (11 females, 9 males; mean age, 33 years) with baseline splenomegaly and thrombocytopenia and/or anemia. Statistically significant (P < .001) percentage improvements from baseline occurred in platelet count (mean ± SD, 81% ± 56%), hemoglobin level (20% ± 15%), spleen volume (-52% ± 11%), and liver volume (-24% ± 13%). Mean platelet count increased ∼ 50 000/mm(3). Mean hemoglobin level increased 2.1 g/dL overall and 3.1 g/dL in 10 patients with baseline anemia. Organ volume reductions were greatest in patients with severe baseline organomegaly. Seventeen (85%) patients met established therapeutic goals for ≥ 3 of the 4 parameters. Lumbar spine bone mineral density increased 7.8% ± 10.6% (P = .01) and T-score 0.6 ± 0.8 (P = .012), with major gains in osteoporotic and osteopenic patients. Magnetic resonance imaging assessment showed that bone marrow infiltration by Gaucher cells was decreased (8/18 patients) or stable (10/18 patients). No safety-related trends emerged during 2 years of treatment. This multisite, open-label, single-arm phase 2 study is registered at www.clinicaltrials.gov as NCT00358150.
authors: Hematology Research Center, Russian Academy of Medical Sciences, Moscow, Russia;
authors: Elena
authors: E
authors: Lukina
authors: Nora
authors: N
authors: Watman
authors: Elsa Avila
authors: EA
authors: Arreguin
authors: Marta
authors: M
authors: Dragosky
authors: Marcelo
authors: M
authors: Iastrebner
authors: Hanna
authors: H
authors: Rosenbaum
authors: Mici
authors: M
authors: Phillips
authors: Gregory M
authors: GM
authors: Pastores
authors: Ravi S
authors: RS
authors: Kamath
authors: Daniel I
authors: DI
authors: Rosenthal
authors: Mathilde
authors: M
authors: Kaper
authors: Tejdip
authors: T
authors: Singh
authors: Ana Cristina
authors: AC
authors: Puga
authors: M Judith
authors: MJ
authors: Peterschmitt
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005776:Gaucher Disease / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D014781:Viscera / Q000187:drug effects / Q000473:pathology*; D055815:Young Adult
chemical_list: D004791:Enzyme Inhibitors; D011759:Pyrrolidines; C522917:eliglustat