Eliglustat, an investigational oral therapy for Gaucher disease type 1: Phase 2 trial results after 4 years of treatment

Elena Lukina; Nora Watman; Marta Dragosky; Gregory M Pastores; Elsa Avila Arreguin; Hanna Rosenbaum; Ari Zimran; Jennifer Angell; Leorah Ross; Ana Cristina Puga; Judith M Peterschmitt

doi:10.1016/j.bcmd.2014.04.002

Eliglustat, an investigational oral therapy for Gaucher disease type 1: Phase 2 trial results after 4 years of treatment

Blood Cells Mol Dis. 2014 Dec;53(4):274-6. doi: 10.1016/j.bcmd.2014.04.002. Epub 2014 May 15.

Authors

Affiliations

¹ Hematology Research Center of Ministry of Healthcare of the Russian Federation, Novy Zykovsky proezd 4, 125167 Moscow, Russia. Electronic address: [email protected].
² Hospital Ramos Mejia, Urquiza 609, Buenos Aires, Argentina. Electronic address: [email protected].
³ Instituto Argentino de Diagnostico y Tratamiento, Marcelo T. de Alvear 2346/2400, Buenos Aires, Argentina. Electronic address: [email protected].
⁴ National Gaucher Disease Treatment Center: Yale Lysosomal Disease Center, 333 Cedar Street, 1080 LMP, New Haven, CT 06519, USA. Electronic address: [email protected].
⁵ Instituto Mexicano del Seguro Social, Hospital de Especialidades, Seris y Zaachila S/N, Mexico City, Mexico. Electronic address: [email protected].
⁶ Hematology Ambulatory Services, Rambam Medical Center, 8 Haaliya St, Haifa 31096, Israel. Electronic address: [email protected].
⁷ Shaare Zedek Medical Center, Gaucher Unit Floor 5, POB 3235, One Bezek Road, Jerusalem 91031, Israel. Electronic address: [email protected].
⁸ Genzyme, a Sanofi company, 500 Kendall Street, Cambridge, MA, 02142, USA. Electronic address: [email protected].
⁹ Genzyme, a Sanofi company, 500 Kendall Street, Cambridge, MA, 02142, USA. Electronic address: [email protected].
¹⁰ Genzyme, a Sanofi company, 500 Kendall Street, Cambridge, MA, 02142, USA. Electronic address: [email protected].
¹¹ Genzyme, a Sanofi company, 500 Kendall Street, Cambridge, MA, 02142, USA. Electronic address: [email protected].

PMID: 24835462
DOI: 10.1016/j.bcmd.2014.04.002

Abstract

Eliglustat is an investigational, oral substrate reduction therapy for Gaucher disease type 1 (GD1). Nineteen treatment-naïve patients have now completed 4years of an open-label study (NCT00358150). Mean hemoglobin level and platelet count increased by 2.3±1.5g/dL (baseline: 11.3±1.5g/dL) and 95% (baseline: 68,700±21,200/mm(3)), respectively. Mean spleen and liver volumes (multiples of normal, MN) decreased by 63% (baseline: 17.3±9.5 MN) and 28% (baseline: 1.7±0.4 MN), respectively. Median chitotriosidase and CCL-18 each decreased by 82%; plasma glucosylceramide and GM3 normalized. Mean bone mineral density T-score for the lumbar spine increased by 0.8 (60%) (baseline: -1.6±1.1). Femur dark marrow, a reflection of Gaucher cell infiltration into bone marrow, was reduced or stable in 17/18 patients. There were no bone crises. Most adverse events were mild and unrelated to treatment. These results extend the safety and efficacy of eliglustat reported at 1 and 2 years to 4 years.

Keywords: Acid β-glucosidase deficiency; Eliglustat; Gaucher disease type 1; Substrate reduction therapy.

Publication types

Clinical Trial, Phase II
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Bone Density
Bone Marrow / drug effects
Bone Marrow / pathology
Chemokines, CC / blood
Drugs, Investigational / therapeutic use*
Enzyme Inhibitors / therapeutic use*
Female
Follow-Up Studies
G(M3) Ganglioside / blood
Gaucher Disease / blood
Gaucher Disease / drug therapy*
Gaucher Disease / pathology
Glucosylceramides / blood
Hemoglobins / metabolism
Hexosaminidases / blood
Humans
Lumbar Vertebrae / drug effects
Male
Middle Aged
Platelet Count
Pyrrolidines / therapeutic use*

Substances

CCL18 protein, human
Chemokines, CC
Drugs, Investigational
Enzyme Inhibitors
G(M3) Ganglioside
Glucosylceramides
Hemoglobins
Pyrrolidines
eliglustat
Hexosaminidases
chitotriosidase

Associated data

ClinicalTrials.gov/NCT00358150