Outcomes after 18 months of eliglustat therapy in treatment-naïve adults with Gaucher disease type 1: The phase 3 ENGAGE trial

Pramod K. Mistry, Elena Lukina, Hadhami Ben Turkia, Suma Shankar, Hagit Baris, Marwan Ghosn, Atul Mehta, Seymour Packman, Gregory Pastores, Milan Petakov, Sarit Assouline, Manisha Balwani, Sumita Danda, Evgueniy Hadjiev, Andres Ortega, Sebastiaan J.M. Gaemers, Regina Tayag, M. Judith Peterschmitt

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Eliglustat, an oral substrate reduction therapy, is a first-line treatment for adults with Gaucher disease type 1 (GD1) who are poor, intermediate, or extensive CYP2D6 metabolizers (>90% of patients). In the primary analysis of the Phase 3 ENGAGE trial (NCT00891202), eliglustat treatment for 9 months resulted in significant reductions in spleen and liver volumes and increases in hemoglobin concentration and platelet count compared with placebo. We report 18-month outcomes of patients who entered the trial extension period, in which all patients received eliglustat. Of 40 trial patients, 39 entered the extension period, and 38 completed 18 months. Absolute values and percent change over time were determined for spleen and liver volume, hemoglobin concentration, platelet count, bone mineral density, bone marrow burden, and Gaucher disease biomarkers. For patients randomized to eliglustat in the double-blind period, continuing treatment with eliglustat for 9 more months resulted in incremental improvement of all disease parameters. For patients randomized to placebo in the double-blind period, eliglustat treatment during the 9-month, open-label period resulted in significant decrease of spleen and liver volumes and significant increase of hemoglobin and platelets, with a similar rate of change to patients who had received eliglustat in the double-blind period. Eliglustat treatment was also associated with improvement in bone marrow burden score, bone mineral density, and established biomarkers of Gaucher disease, including reduction of the bioactive lipid, glucosylsphingosine. These findings underscore the efficacy of eliglustat in treatment-naïve patients. Eliglustat was well-tolerated, and there were no new safety concerns with longer-term exposure.

Original languageEnglish (US)
Pages (from-to)1170-1176
Number of pages7
JournalAmerican Journal of Hematology
Volume92
Issue number11
DOIs
StatePublished - Nov 1 2017

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Gaucher Disease
Therapeutics
Hemoglobins
Spleen
Platelet Count
Bone Density
Liver
Biomarkers
Bone Marrow Diseases
Placebos
eliglustat
Cytochrome P-450 CYP2D6
Blood Platelets
Bone Marrow
Lipids
Safety

ASJC Scopus subject areas

  • Hematology

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Outcomes after 18 months of eliglustat therapy in treatment-naïve adults with Gaucher disease type 1 : The phase 3 ENGAGE trial. / Mistry, Pramod K.; Lukina, Elena; Ben Turkia, Hadhami; Shankar, Suma; Baris, Hagit; Ghosn, Marwan; Mehta, Atul; Packman, Seymour; Pastores, Gregory; Petakov, Milan; Assouline, Sarit; Balwani, Manisha; Danda, Sumita; Hadjiev, Evgueniy; Ortega, Andres; Gaemers, Sebastiaan J.M.; Tayag, Regina; Peterschmitt, M. Judith.

In: American Journal of Hematology, Vol. 92, No. 11, 01.11.2017, p. 1170-1176.

Research output: Contribution to journalArticle

Mistry, PK, Lukina, E, Ben Turkia, H, Shankar, S, Baris, H, Ghosn, M, Mehta, A, Packman, S, Pastores, G, Petakov, M, Assouline, S, Balwani, M, Danda, S, Hadjiev, E, Ortega, A, Gaemers, SJM, Tayag, R & Peterschmitt, MJ 2017, 'Outcomes after 18 months of eliglustat therapy in treatment-naïve adults with Gaucher disease type 1: The phase 3 ENGAGE trial', American Journal of Hematology, vol. 92, no. 11, pp. 1170-1176. https://doi.org/10.1002/ajh.24877
Mistry, Pramod K. ; Lukina, Elena ; Ben Turkia, Hadhami ; Shankar, Suma ; Baris, Hagit ; Ghosn, Marwan ; Mehta, Atul ; Packman, Seymour ; Pastores, Gregory ; Petakov, Milan ; Assouline, Sarit ; Balwani, Manisha ; Danda, Sumita ; Hadjiev, Evgueniy ; Ortega, Andres ; Gaemers, Sebastiaan J.M. ; Tayag, Regina ; Peterschmitt, M. Judith. / Outcomes after 18 months of eliglustat therapy in treatment-naïve adults with Gaucher disease type 1 : The phase 3 ENGAGE trial. In: American Journal of Hematology. 2017 ; Vol. 92, No. 11. pp. 1170-1176.
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AU - Ben Turkia, Hadhami

AU - Shankar, Suma

AU - Baris, Hagit

AU - Ghosn, Marwan

AU - Mehta, Atul

AU - Packman, Seymour

AU - Pastores, Gregory

AU - Petakov, Milan

AU - Assouline, Sarit

AU - Balwani, Manisha

AU - Danda, Sumita

AU - Hadjiev, Evgueniy

AU - Ortega, Andres

AU - Gaemers, Sebastiaan J.M.

AU - Tayag, Regina

AU - Peterschmitt, M. Judith

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