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

Volumn 92, Issue 11, 2017, Pages 1170-1176

  Mistry, Pramod K ^a   Lukina, Elena ^b   Ben Turkia, Hadhami ^c   Shankar, Suma P ^d,u   Baris, Hagit ^e,f,g   Ghosn, Marwan ^h   Mehta, Atul ⁱ   Packman, Seymour ^j   Pastores, Gregory ^k,v   Petakov, Milan ^l   Assouline, Sarit ^m   Balwani, Manisha ⁿ   Danda, Sumita ^o   Hadjiev, Evgueniy ^p   Ortega, Andres ^q   Gaemers, Sebastiaan J M ^r   Tayag, Regina ^s   Peterschmitt, M Judith ^t  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b NATIONAL RESEARCH CENTER FOR HEMATOLOGY   (Russian Federation)

^c LA RABTA HOSPITAL   (Tunisia)

^d EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e RABIN MEDICAL CENTER   (Israel)

^f TEL AVIV UNIVERSITY   (Israel)

^g TECHNION ISRAEL INSTITUTE OF TECHNOLOGY   (Israel)

^h SAINT JOSEPH UNIVERSITY   (Lebanon)

ⁱ UNIVERSITY COLLEGE LONDON   (United Kingdom)

^j UNIVERSITY OF CALIFORNIA   (United States)

^k NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

^l UNIVERSITY OF BELGRADE   (Serbia)

^m MCGILL UNIVERSITY   (Canada)

ⁿ MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^o CHRISTIAN MEDICAL COLLEGE   (India)

^p MEDICAL UNIVERSITY OF SOFIA   (Bulgaria)

^q Oca Hospital   (Mexico)

^r Genzyme Corp (A Sanofi Company)   (Netherlands)

^s PROMETRIKA LLC   (United States)

^t GENZYME CORPORATION   (United States)

^u UNIVERSITY OF CALIFORNIA   (United States)

^v UNIVERSITY COLLEGE DUBLIN   (Ireland)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ELIGLUSTAT; HEMOGLOBIN; PLACEBO; ENZYME INHIBITOR; GLUCOSYLCERAMIDASE; PYRROLIDINE DERIVATIVE;

ABDOMINAL DISTENSION; ABDOMINAL PAIN; ADULT; ARTICLE; BONE DENSITY; BONE MARROW; CLINICAL ARTICLE; CLINICAL ASSESSMENT; CONTROLLED STUDY; DIARRHEA; DIZZINESS; DOUBLE BLIND PROCEDURE; DYSPEPSIA; FLATULENCE; GAUCHER DISEASE TYPE 1; HEADACHE; HEMOGLOBIN BLOOD LEVEL; HEMOGLOBIN DETERMINATION; HUMAN; HUMAN TISSUE; LIVER WEIGHT; NAUSEA; OPEN STUDY; OUTCOME ASSESSMENT; PHASE 3 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SECOND DEGREE ATRIOVENTRICULAR BLOCK; SPLEEN WEIGHT; THROMBOCYTE COUNT; TREATMENT DURATION; XEROSTOMIA; ANTAGONISTS AND INHIBITORS; CLINICAL TRIAL; ENZYME REPLACEMENT; ENZYMOLOGY; FOLLOW UP; GAUCHER DISEASE; LIVER; ORGAN SIZE; PATHOLOGY; SPLEEN; TREATMENT OUTCOME;

ENZYME INHIBITORS; ENZYME REPLACEMENT THERAPY; FOLLOW-UP STUDIES; GAUCHER DISEASE; GLUCOSYLCERAMIDASE; HUMANS; LIVER; ORGAN SIZE; PYRROLIDINES; SPLEEN; TREATMENT OUTCOME;

EID: 85030439861     PISSN: 03618609     EISSN: 10968652     Source Type: Journal    
DOI: 10.1002/ajh.24877     Document Type: Article

References (17)

1. Grabowski GA, Petsko GA, Kolodny EH. Gaucher disease. In: Valle D, Beaudet AL, Vogelstein B, et al., eds. OMMBID: The Online Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGraw-Hill; 2013.
2. Pandey MK, Burrow TA, Rani R, et al. Complement drives glucosylceramide accumulation and tissue inflammation in Gaucher disease. Nature. 2017;543:108–112.
3. Mistry PK, Liu J, Yang M, et al. Glucocerebrosidase gene-deficient mouse recapitulates Gaucher disease displaying cellular and molecular dysregulation beyond the macrophage. Proc Natl Acad Sci USA. 2010;107:19473–19478.
4. Shayman JA. Eliglustat tartrate: glucosylceramide synthase inhibitor treatment. Drugs Future. 2010;35:613–620.
5. CERDELGA (eliglustat) [package insert]. Waterford, Ireland: Genzyme Corporation, a Sanofi Company; August 2014.
6. Peterschmitt MJ, Cox GF, Ibrahim J, et al. A pooled analysis of adverse events in 393 adults with Gaucher disease type 1 from four clinical trials of oral eliglustat: evaluation of frequency, timing, and duration. Blood Cells Mol Dis. 2017; Jan 13, doi:10.1016/j.bcmd.2017.01.006, epub ahead of print.
7. Mistry PK, Lukina E, Ben Turkia H, et al. Effect of oral eliglustat on splenomegaly in patients with Gaucher disease type 1: the ENGAGE randomized clinical trial. JAMA. 2015;313:695–706.
8. Lukina E, Watman N, Dragosky M, et al. Eliglustat, an investigational oral therapy for Gaucher disease type 1: phase 2 trial results after 4 years of treatment. Blood Cells Mol Dis. 2014;53:274–276.
9. Murugesan V, Chuang WL, Liu J, et al. Glucosylsphingosine is a key biomarker of Gaucher disease. Am J Hematol. 2016;91:1082–1089.
10. Dekker N, van Dussen L, Hollak CE, et al. Elevated plasma glucosylsphingosine in Gaucher disease: relation to phenotype, storage cell markers, and therapeutic response. Blood. 2011;118:e118–e127.
11. Nair S, Boddupalli CS, Verma R, et al. Type II NKT-TFH cells against Gaucher lipids regulate B-cell immunity and inflammation. Blood. 2015;125:1256–1271.
12. Nair S, Branagan AR, Liu J, et al. Clonal immunoglobulin against lysolipids in the origin of myeloma. N Engl J Med. 2016;374:555–561.
13. van Breemen MJ, de Fost M, Voerman JS, et al. Increased plasma macrophage inflammatory protein (MIP)-1alpha and MIP-1beta levels in type 1 Gaucher disease. Biochim Biophys Acta. 2007;1772:788–796.
14. Lukina E, Watman N, Arreguin EA, et al. A Phase 2 study of eliglustat tartrate (Genz-112638), an oral substrate reduction therapy for Gaucher disease type 1. Blood. 2010;116:893–899.
15. Lukina E, Watman N, Arreguin EA, et al. 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. Blood. 2010;116:4095–4098.
16. Cox TM, Drelichman G, Cravo R, et al. Eliglustat compared with imiglucerase in patients with Gaucher's disease type 1 stabilised on enzyme replacement therapy: a phase 3, randomised, open-label, non-inferiority trial. Lancet. 2015;385:2355–2362.
17. Cox TM, Drelichman G, Cravo R, et al. Eliglustat maintains long-term clinical stability in patients with Gaucher disease type 1 stabilized on enzyme therapy. Blood. 2017;129:2375–2383.