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: Elena Lukina, Nora Watman, Elsa Avila Arreguin, Marta Dragosky, Marcelo Iastrebner, Hanna Rosenbaum, Mici Phillips, Gregory M Pastores, Ravi S Kamath, Daniel I Rosenthal, Mathilde Kaper, Tejdip Singh, Ana Cristina Puga, M Judith Peterschmitt
• Journal: Blood (Blood) Vol. 116 Issue 20 Pg. 4095-8 (Nov 18 2010) ISSN: 1528-0020 [Electronic] United States
• PMID: 20713962 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Pyrrolidines
• eliglustat

Topics

• Administration, Oral
• Adolescent
• Adult
• Bone and Bones (drug effects, pathology)
• Enzyme Inhibitors (administration & dosage, pharmacology, therapeutic use)
• Female
• Gaucher Disease (blood, drug therapy)
• Humans
• Male
• Middle Aged
• Pyrrolidines (administration & dosage, pharmacology, therapeutic use)
• Viscera (drug effects, pathology)
• Young Adult