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.
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.
Lukina
Elena
E
Hematology Research Center, Russian Academy of Medical Sciences, Moscow, Russia;
Watman
Nora
N
Arreguin
Elsa Avila
EA
Dragosky
Marta
M
Iastrebner
Marcelo
M
Rosenbaum
Hanna
H
Phillips
Mici
M
Pastores
Gregory M
GM
Kamath
Ravi S
RS
Rosenthal
Daniel I
DI
Kaper
Mathilde
M
Singh
Tejdip
T
Puga
Ana Cristina
AC
Peterschmitt
M Judith
MJ
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
D004791:Enzyme Inhibitors; D011759:Pyrrolidines; C522917:eliglustat