Eliglustat maintains long-term clinical stability in patients with Gaucher disease type 1 stabilized on enzyme therapy.
In the phase 3 Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease Who Have Reached Therapeutic Goals With Enzyme Replacement Therapy (ENCORE), at 1 year, eliglustat was noninferior to imiglucerase enzyme therapy in maintaining stable platelet counts, hemoglobin concentrations, and spleen and liver volumes. After this primary analysis period, patients entered a long-term extension phase in which all received eliglustat. Duration on eliglustat ranged from 2 to 5 years, depending on timing of enrollment (which spanned 2 years), treatment group to which patients were randomized, and whether they lived in the United States when commercial eliglustat became available. Here we report long-term safety and efficacy of eliglustat for 157 patients who received eliglustat in the ENCORE trial; data are available for 46 patients who received eliglustat for 4 years. Mean hemoglobin concentration, platelet count, and spleen and liver volumes remained stable for up to 4 years. Year to year, all 4 measures remained collectively stable (composite end point relative to baseline values) in ≥85% of patients as well as individually in ≥92%. Mean bone mineral density z scores (lumbar spine and femur) remained stable and were maintained in the healthy reference range throughout. Eliglustat was well tolerated over 4 years; 4 (2.5%) patients withdrew because of adverse events that were considered related to the study drug. No new or long-term safety concerns were identified. Clinical stability assessed by composite and individual measures was maintained in adults with Gaucher disease type 1 treated with eliglustat who remained in the ENCORE trial for up to 4 years. This trial was registered at www.clinicaltrials.gov as #NCT00943111.
Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
Timothy M
TM
Cox
Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina.
Guillermo
G
Drelichman
State Institute of Haematology "Arthur de Siqueira Cavalcanti," Rio de Janeiro, Brazil.
Renata
R
Cravo
Mount Sinai Hospital, New York, NY.
Manisha
M
Balwani
Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Thomas Andrew
TA
Burrow
Universidade Federal de São Paulo, São Paulo, Brazil.
Ana Maria
AM
Martins
National Research Center for Hematology, Moscow, Russia.
Elena
E
Lukina
Cedars-Sinai/Tower Hematology Oncology, Beverly Hills, CA.
Barry
B
Rosenbloom
Lysosomal Disorders Unit, O&O Alpan, LLC, Fairfax, VA.
Ozlem
O
Goker-Alpan
Hospital Ramos Mejia, Buenos Aires, Argentina.
Nora
N
Watman
Pediatric Hematology, Cairo University, Cairo, Egypt.
Amal
A
El-Beshlawy
Department of Pediatrics, Duke University School of Medicine, Durham, NC.
Priya S
PS
Kishnani
Gastroenterology Department, Universidade Federal do Paraná, Curitiba, Brazil.
Maria Lucia
ML
Pedroso
Sanofi Genzyme, Cambridge, MA; and.
Sebastiaan J M
SJM
Gaemers
Prometrika LLC, Cambridge, MA.
Regina
R
Tayag
Sanofi Genzyme, Cambridge, MA; and.
M Judith
MJ
Peterschmitt
D000284:Administration, Oral; D000328:Adult; D015519:Bone Density / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D056947:Enzyme Replacement Therapy; D005260:Female; D005269:Femur / Q000187:drug effects / Q000201:enzymology; D005776:Gaucher Disease / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D005962:Glucosylceramidase / Q000627:therapeutic use*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011759:Pyrrolidines / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use*; D013154:Spleen / Q000187:drug effects / Q000201:enzymology
D004791:Enzyme Inhibitors; D011759:Pyrrolidines; D011994:Recombinant Proteins; C522917:eliglustat; D005962:Glucosylceramidase; C090568:imiglucerase