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

The Lancet

Volumn 385, Issue 9985, 2015, Pages 2355-2362

  Cox, Timothy M ^a   Drelichman, Guillermo ^b   Cravo, Renata ^c   Balwani, Manisha ^d   Burrow, Thomas Andrew ^e   Martins, Ana Maria ^f   Lukina, Elena ^g   Rosenbloom, Barry ^h   Ross, Leorah ⁱ   Angell, Jennifer ⁱ   Puga, Ana Cristina ⁱ  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b HOSPITAL DE NIÑOS RICARDO GUTIÉRREZ   (Argentina)

^c State Institute of Haematology 'Arthur de Siqueira Cavalcanti'   (Brazil)

^d MOUNT SINAI HOSPITAL   (United States)

^e CINCINNATI CHILDREN'S HOSPITAL MEDICAL CENTER   (United States)

^f FEDERAL UNIVERSITY OF SÃO PAULO   (Brazil)

^g NATIONAL RESEARCH CENTER FOR HEMATOLOGY   (Russian Federation)

^h and Tower Hematology Oncology ^*  (United States)

ⁱ GENZYME CORPORATION   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

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

ADULT; ARTHRALGIA; ARTICLE; ASTHENIA; BACKACHE; BONE PAIN; CONFUSION; CONSTIPATION; CONTROLLED STUDY; COUGHING; DIARRHEA; DIZZINESS; DYSPEPSIA; ENZYME REPLACEMENT; EPISTAXIS; FATIGUE; FEMALE; GASTROESOPHAGEAL REFLUX; GAUCHER DISEASE; HEADACHE; HEART INFARCTION; HEART PALPITATION; HEMOGLOBIN DETERMINATION; HEPATOMEGALY; HUMAN; INFLUENZA; LIMB PAIN; LIVER WEIGHT; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; ORGAN SIZE; PATIENT DROPOUTS; PHASE 3 CLINICAL TRIAL; PRIORITY JOURNAL; PSYCHOSIS; RANDOMIZED CONTROLLED TRIAL; RASH; RHINOPHARYNGITIS; SPLEEN; THROMBOCYTE COUNT; TOOTH PAIN; TREATMENT OUTCOME; UPPER ABDOMINAL PAIN; UPPER RESPIRATORY TRACT INFECTION; URINARY TRACT INFECTION; VIRAL GASTROENTERITIS; BLOOD; CLINICAL TRIAL; INTRAVENOUS DRUG ADMINISTRATION; LIVER; NUCLEAR MAGNETIC RESONANCE IMAGING; ORAL DRUG ADMINISTRATION; PATHOLOGY;

ADMINISTRATION, ORAL; ADULT; ENZYME INHIBITORS; ENZYME REPLACEMENT THERAPY; FEMALE; GAUCHER DISEASE; GLUCOSYLCERAMIDASE; HEMOGLOBINS; HUMANS; INFUSIONS, INTRAVENOUS; LIVER; MAGNETIC RESONANCE IMAGING; MALE; ORGAN SIZE; PLATELET COUNT; PYRROLIDINES; SPLEEN;

EID: 84930932122     PISSN: 01406736     EISSN: 1474547X     Source Type: Journal    
DOI: 10.1016/S0140-6736(14)61841-9     Document Type: Article

References (34)

1. G Grabowski, EH Kolodny, N Weinreb Gaucher disease: phenotypic and genetic variation CR Scriver AL Beaudet D Valle The online metabolic and molecular basis of inherited metabolic disease 2006 McGraw-Hill Companies New York
2. M Chen, J Wang Gaucher disease: review of the literature Arch Pathol Lab Med 132 2008 851 853
3. GA Grabowski Phenotype, diagnosis, and treatment of Gaucher's disease Lancet 372 2008 1263 1271
4. PK Mistry, P Deegan, A Vellodi, JA Cole, M Yeh, NJ Weinreb Timing of initiation of enzyme replacement therapy after diagnosis of type 1 Gaucher disease: effect on incidence of avascular necrosis Br J Haematol 147 2009 561 570
5. PB Deegan, E Pavlova, J Tindall et al. Osseous manifestations of adult Gaucher disease in the era of enzyme replacement therapy Medicine (Baltimore) 90 2011 52 60
6. P Kaplan, H Baris, L De Meirleir et al. Revised recommendations for the management of Gaucher disease in children Eur J Pediatr 172 2013 447 458
7. KA McEachern, J Fung, S Komarnitsky et al. A specific and potent inhibitor of glucosylceramide synthase for substrate inhibition therapy of Gaucher disease Mol Genet Metab 91 2007 259 267
8. TM Cox, D Amato, CE Hollak et al. Evaluation of miglustat as maintenance therapy after enzyme therapy in adults with stable type 1 Gaucher disease: a prospective, open-label non-inferiority study Orphanet J Rare Dis 7 2012 102
9. Zavesca package insert http://www.accessdata.fda.gov/drugsatfda-docs/label/2008/021348s005lbl.pdf Feb, 2008 (accessed April 23, 2014).
10. Zavesca of product characteristics http://www.ema.europa.eu/docs/en-GB/document-library/EPAR-Product-Information/human/000435/WC500046726.pdf 2013 (accessed April 23, 2014).
11. RS Kamath, E Lukina, N Watman et al. Skeletal improvement in patients with Gaucher disease type 1: a phase 2 trial of oral eliglustat Skeletal Radiol 43 2014 1353 1360
12. E Lukina, N Watman, EA Arreguin et al. A phase 2 study of eliglustat tartrate (Genz-112638), an oral substrate reduction therapy for Gaucher disease type 1 Blood 116 2010 893 899
13. E Lukina, N Watman, EA Arreguin 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 116 2010 4095 4098
14. E Lukina, N Watman, M Dragosky 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 53 2014 274 276
15. PK Mistry, E Lukina, H Ben Turkia et al. Effect of oral eliglustat on splenomegaly in patients with Gaucher disease type 1: the ENGAGE randomized clinical trial JAMA 313 2015 695 706
16. NW Barton, RO Brady, JM Dambrosia et al. Replacement therapy for inherited enzyme deficiency - macrophage-targeted glucocerebrosidase for Gaucher's disease N Engl J Med 324 1991 1464 1470
17. PS Kishnani, M DiRocco, P Kaplan et al. A randomized trial comparing the efficacy and safety of imiglucerase (Cerezyme) infusions every 4 weeks versus every 2 weeks in the maintenance therapy of adult patients with Gaucher disease type 1 Mol Genet Metab 96 2009 164 170
18. M Maas, T Hangartner, G Mariani et al. Recommendations for the assessment and monitoring of skeletal manifestations in children with Gaucher disease Skeletal Radiol 37 2008 185 188
19. PL Robertson, M Maas, J Goldblatt Semiquantitative assessment of skeletal response to enzyme replacement therapy for Gaucher's disease using the bone marrow burden score AJR Am J Roentgenol 188 2007 1521 1528
20. K Haddley Taliglucerase alfa for the treatment of Gaucher's disease Drugs Today (Barc) 48 2012 525 532
21. CE Hollak An evidence-based review of the potential benefits of taliglucerase alfa in the treatment of patients with Gaucher disease Core Evid 7 2012 15 20
22. A Agresti, B Caffo Simple and effective confidence intervals for proportions and difference of proportions results from adding two successes and two failures Am Stat 54 2000 280 288
23. RS Dann, GG Koch Methods for one-sided testing of the difference between proportions and sample size considerations related to non-inferiority clinical trials Pharm Stat 7 2008 130 141
24. GM Pastores, NJ Weinreb, H Aerts et al. Therapeutic goals in the treatment of Gaucher disease Semin Hematol 41 4 suppl 5 2004 4 14
25. NJ Weinreb, RE Lee Causes of death due to hematological and non-hematological cancers in 57 US patients with type 1 Gaucher Disease who were never treated with enzyme replacement therapy Crit Rev Oncog 18 2013 177 195
26. TH Taddei, J Dziura, S Chen et al. High incidence of cholesterol gallstone disease in type 1 Gaucher disease: characterizing the biliary phenotype of type 1 Gaucher disease J Inherit Metab Dis 33 2010 291 300
27. D Elstein, A Dweck, D Attias et al. Oral maintenance clinical trial with miglustat for type I Gaucher disease: switch from or combination with intravenous enzyme replacement Blood 110 2007 2296 2301
28. P Giraldo, P Alfonso, K Atutxa et al. Real-world clinical experience with long-term miglustat maintenance therapy in type 1 Gaucher disease: the ZAGAL project Haematologica 94 2009 1771 1775
29. P Giraldo, P Latre, P Alfonso et al. Short-term effect of miglustat in every day clinical use in treatment-naive or previously treated patients with type 1 Gaucher's disease Haematologica 91 2006 703 706
30. DL Kuter, A Mehta, CE Hollak et al. Miglustat therapy in type 1 Gaucher disease: clinical and safety outcomes in a multicenter retrospective cohort study Blood Cells Mol Dis 51 2013 116 124
31. Cerezyme of product characteristics http://www.ema.europa.eu/docs/en-GB/document-library/EPAR-Product-Information/human/000157/WC500024112.pdf 2009 (accessed April 23, 2014).
32. T Cox, R Lachmann, C Hollak et al. Novel oral treatment of Gaucher's disease with N-butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis Lancet 355 2000 1481 1485
33. DJ Ross, S Spira, NA Buchbinder Gaucher cells in pulmonary-capillary blood in association with pulmonary hypertension N Engl J Med 336 1997 379 381
34. PK Mistry, EP Wraight, TM Cox Therapeutic delivery of proteins to macrophages: implications for treatment of Gaucher's disease Lancet 348 1996 1555 1559