Eliglustat, an investigational oral therapy for Gaucher disease type 1: Phase 2 trial results after 4 years of treatment.
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.
Hematology Research Center of Ministry of Healthcare of the Russian Federation, Novy Zykovsky proezd 4, 125167 Moscow, Russia. Electronic address: kira-l@mail.ru.
Elena
E
Lukina
Hospital Ramos Mejia, Urquiza 609, Buenos Aires, Argentina. Electronic address: npwatman@yahoo.com.ar.
Nora
N
Watman
Instituto Argentino de Diagnostico y Tratamiento, Marcelo T. de Alvear 2346/2400, Buenos Aires, Argentina. Electronic address: marta@dragosky.com.ar.
Marta
M
Dragosky
National Gaucher Disease Treatment Center: Yale Lysosomal Disease Center, 333 Cedar Street, 1080 LMP, New Haven, CT 06519, USA. Electronic address: gregory.pastores@yale.edu.
Gregory M
GM
Pastores
Instituto Mexicano del Seguro Social, Hospital de Especialidades, Seris y Zaachila S/N, Mexico City, Mexico. Electronic address: elsa.avila@yahoo.com.mx.
Elsa Avila
EA
Arreguin
Hematology Ambulatory Services, Rambam Medical Center, 8 Haaliya St, Haifa 31096, Israel. Electronic address: h_rosenbaum@rambam.health.gov.il.
Hanna
H
Rosenbaum
Shaare Zedek Medical Center, Gaucher Unit Floor 5, POB 3235, One Bezek Road, Jerusalem 91031, Israel. Electronic address: azimran@gmail.com.
Ari
A
Zimran
Genzyme, a Sanofi company, 500 Kendall Street, Cambridge, MA, 02142, USA. Electronic address: Jennifer.Shannon@genzyme.com.
Jennifer
J
Angell
Genzyme, a Sanofi company, 500 Kendall Street, Cambridge, MA, 02142, USA. Electronic address: Leorah.Ross@genzyme.com.
Leorah
L
Ross
Genzyme, a Sanofi company, 500 Kendall Street, Cambridge, MA, 02142, USA. Electronic address: AnaCristina.Puga@genzyme.com.
Ana Cristina
AC
Puga
Genzyme, a Sanofi company, 500 Kendall Street, Cambridge, MA, 02142, USA. Electronic address: Judith.Peterschmitt@genzyme.com.
Judith M
JM
Peterschmitt
D000293:Adolescent; D000328:Adult; D015519:Bone Density; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D019742:Chemokines, CC / Q000097:blood; D015507:Drugs, Investigational / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005679:G(M3) Ganglioside / Q000097:blood; D005776:Gaucher Disease / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D005963:Glucosylceramides / Q000097:blood; D006454:Hemoglobins / Q000378:metabolism; D006596:Hexosaminidases / Q000097:blood; D006801:Humans; D008159:Lumbar Vertebrae / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011759:Pyrrolidines / Q000627:therapeutic use*
C111792:CCL18 protein, human; D019742:Chemokines, CC; D015507:Drugs, Investigational; D004791:Enzyme Inhibitors; D005679:G(M3) Ganglioside; D005963:Glucosylceramides; D006454:Hemoglobins; D011759:Pyrrolidines; C522917:eliglustat; D006596:Hexosaminidases; C086400:chitotriosidase
Acid β-glucosidase deficiency; Eliglustat; Gaucher disease type 1; Substrate reduction therapy