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, Molecules, and Diseases

Volumn 68, Issue , 2018, Pages 185-191

  Peterschmitt, M Judith ^a   Cox, Gerald F ^a,c   Ibrahim, Jennifer ^a   MacDougall, James ^b   Underhill, Lisa H ^a   Patel, Palni ^a   Gaemers, Sebastiaan J M ^a  

^a GENZYME CORPORATION   (United States)

^b PROMETRIKA LLC   (United States)

^c EDITAS MEDICINE   (United States)

Author keywords

Acid glucosidase deficiency; Adverse events; Eliglustat; Gaucher disease type 1; Safety; Substrate reduction therapy

Indexed keywords

ELIGLUSTAT; ENZYME INHIBITOR; PYRROLIDINE DERIVATIVE;

ABDOMINAL PAIN; ADULT; ADVERSE OUTCOME; ARTHRALGIA; ARTICLE; CYANOCOBALAMIN DEFICIENCY; DIABETES MELLITUS; DIARRHEA; DISEASE DURATION; DISEASE SEVERITY; DIZZINESS; DRUG EFFICACY; DRUG RESPONSE; DRUG WITHDRAWAL; FATIGUE; FEMALE; FLATULENCE; GAUCHER DISEASE; HASHIMOTO DISEASE; HEADACHE; HEART PALPITATION; HUMAN; HYPOTHYROIDISM; MAJOR CLINICAL STUDY; MALE; MONOCLONAL IMMUNOGLOBULINEMIA; NAUSEA; OUTCOME ASSESSMENT; PERIPHERAL NEUROPATHY; PRIORITY JOURNAL; RHINOPHARYNGITIS; RISK FACTOR; SIDE EFFECT; TREATMENT DURATION; TREATMENT OUTCOME; WEIGHT GAIN; CLINICAL TRIAL; CONTROLLED STUDY; ENZYME REPLACEMENT; MIDDLE AGED; PHASE 2 CLINICAL TRIAL; PHASE 3 CLINICAL TRIAL; RANDOMIZED CONTROLLED TRIAL; YOUNG ADULT;

ADULT; ENZYME INHIBITORS; ENZYME REPLACEMENT THERAPY; FEMALE; GAUCHER DISEASE; HUMANS; MALE; MIDDLE AGED; PYRROLIDINES; YOUNG ADULT;

EID: 85009965868     PISSN: 10799796     EISSN: 10960961     Source Type: Journal    
DOI: 10.1016/j.bcmd.2017.01.006     Document Type: Article

References (27)

1. Grabowski, G.A., Petsko, G.A., Kolodny, E.H., Gaucher disease. Valle, D., Beaudet, A.L., Vogelstein, B., Kinzler, K.W., Antonarakis, S.E., Ballabio, A., Gibson, K., Mitchell, G., (eds.) OMMBID: The Online Metabolic and Molecular Bases of Inherited Disease, 2013, McGraw-Hill, New York, NY Available at: http://ommbid.mhmedical.com/content.aspx?bookid=474&Sectionid=45374148.
2. Grabowski, G.A., Andria, G., Baldellou, A., Campbell, P.E., Charrow, J., Cohen, I.J., Harris, C.M., Kaplan, P., Mengel, E., Pocovi, M., Vellodi, A., Pediatric non-neuronopathic Gaucher disease: presentation, diagnosis and assessment. Consens. Statement Eur. J. Pediatr. 163 (2004), 58–66.
3. Charrow, J., Andersson, H.C., Kaplan, P., Kolodny, E.H., Mistry, P., Pastores, G., Rosenbloom, B.E., Scott, C.R., Wappner, R.S., Weinreb, N.J., Zimran, A., The Gaucher registry: demographics and disease characteristics of 1698 patients with Gaucher disease. Arch. Intern. Med. 160 (2000), 2835–2843.
4. Goker-Alpan, O., Therapeutic approaches to bone pathology in Gaucher disease: past, present and future. Mol. Genet. Metab. 104 (2011), 438–447.
5. Mistry, P.K., Deegan, P., Vellodi, A., Cole, J.A., Yeh, M., Weinreb, N.J., 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.
6. Mistry, P.K., Sirrs, S., Chan, A., Pritzker, M.R., Duffy, T.P., Grace, M.E., Meeker, D.P., Goldman, M.E., Pulmonary hypertension in type 1 Gaucher's disease: genetic and epigenetic determinants of phenotype and response to therapy. Mol. Genet. Metab. 77 (2002), 91–98.
7. Pastores, G.M., Weinreb, N.J., Aerts, H., Andria, G., Cox, T.M., Giralt, M., Grabowski, G.A., Mistry, P.K., Tylki-Szymanska, A., Therapeutic goals in the treatment of Gaucher disease. Semin. Hematol. 41 (2004), 4–14.
8. Terk, M.R., Dardashti, S., Liebman, H.A., Bone marrow response in treated patients with Gaucher disease: evaluation by T1-weighted magnetic resonance images and correlation with reduction in liver and spleen volume. Skelet. Radiol. 29 (2000), 563–571.
9. Mistry, P.K., Weinthal, J.A., Weinreb, N.J., Disease state awareness in Gaucher disease: a Q&A expert roundtable discussion. Clin. Adv. Hematol. Oncol. 10 (2012), 1–16.
10. Grabowski, G.A., Phenotype, diagnosis, and treatment of Gaucher's disease. Lancet 372 (2008), 1263–1271.
11. Lukina, E., Watman, N., Arreguin, E.A., Banikazemi, M., Dragosky, M., Iastrebner, M., Rosenbaum, H., Phillips, M., Pastores, G.M., Rosenthal, D.I., Kaper, M., Singh, T., Puga, A.C., Bonate, P.L., Peterschmitt, M.J., A phase 2 study of eliglustat tartrate (Genz-112638), an oral substrate reduction therapy for Gaucher disease type 1. Blood 116 (2010), 893–899.
12. Lukina, E., Watman, N., Arreguin, E.A., Dragosky, M., Iastrebner, M., Rosenbaum, H., Phillips, M., Pastores, G.M., Kamath, R.S., Rosenthal, D.I., Kaper, M., Singh, T., Puga, A.C., Peterschmitt, M.J., 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.
13. Lukina, E., Watman, N., Dragosky, M., Pastores, G.M., Arreguin, E.A., Rosenbaum, H., Zimran, A., Angell, J., Ross, L., Puga, A.C., Peterschmitt, J.M., 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.
14. Mistry, P.K., Lukina, E., Ben Turkia, H., Amato, D., Baris, H., Dasouki, M., Ghosn, M., Mehta, A., Packman, S., Pastores, G., Petakov, M., Assouline, S., Balwani, M., Danda, S., Hadjiev, E., Ortega, A., Shankar, S., Solano, M.H., Ross, L., Angell, J., Peterschmitt, M.J., Effect of oral eliglustat on splenomegaly in patients with Gaucher disease type 1: the ENGAGE randomized clinical trial. JAMA 313 (2015), 695–706.
15. Cox, T.M., Drelichman, G., Cravo, R., Balwani, M., Burrow, T.A., Martins, A.M., Lukina, E., Rosenbloom, B., Ross, L., Angell, J., Puga, A.C., 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 385 (2015), 2355–2362.
16. CERDELGA™ (eliglustat) [package insert], Genzyme Corporation, a Sanofi Company, Waterford, Ireland, August 2014.
17. CERDELGA™ Summary of Product Characteristics, Genzyme Corporation, a Sanofi Company, Waterford, Ireland, 2014.
18. Zavesca (miglustat) Summary of Product Characteristics, Actelion Pharmaceuticals UK Ltd2013.
19. Zavesca (miglustat) US Prescribing Information Actelion Pharmaceuticals US, Inc, South San Francisco, CA, 2014.
20. Hicks, J.K., Swen, J.J., Thorn, C.F., Sangkuhl, K., Kharasch, E.D., Ellingrod, V.L., Skaar, T.C., Muller, D.J., Gaedigk, A., Stingl, J.C., Clinical Pharmacogenetics Implementation, Clinical Pharmacogenetics Implementation Consortium guideline for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants. Clin. Pharmacol. Ther. 93 (2013), 402–408.
21. Lau, H., Ibrahim, J., Peterschmitt, M.J., Ross, L., Tremor and peripheral neuropathy are infrequent and non-serious events in Gaucher type 1 patients treated with eliglustat [abstract]. Mol. Genet. Metab. 114 (2015), S69–S70.
22. Cox, T.M., Amato, D., Hollak, C.E., Luzy, C., Silkey, M., Giorgino, R., Steiner, R.D., 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.
23. Wennekes, T., Meijer, A.J., Groen, A.K., Boot, R.G., Groener, J.E., van Eijk, M., Ottenhoff, R., Bijl, N., Ghauharali, K., Song, H., O'Shea, T.J., Liu, H., Yew, N., Copeland, D., van den Berg, R.J., van der Marel, G.A., Overkleeft, H.S., Aerts, J.M., Dual-action lipophilic iminosugar improves glycemic control in obese rodents by reduction of visceral glycosphingolipids and buffering of carbohydrate assimilation. J. Med. Chem. 53 (2010), 689–698.
24. Schiffmann, R., Fitzgibbon, E.J., Harris, C., DeVile, C., Davies, E.H., Abel, L., van Schaik, I.N., Benko, W., Timmons, M., Ries, M., Vellodi, A., Randomized, controlled trial of miglustat in Gaucher's disease type 3. Ann. Neurol. 64 (2008), 514–522.
25. Shayman, J.A., Eliglustat tartrate: glucosylceramide synthase inhibitor treatment of type 1 Gaucher disease. Drugs Future 35 (2010), 613–620.
26. Peterschmitt, M.J., Ruskin, J.N., Ortemann-Renon, C., Ross, L., Mankoski, R., Puga, A.C., von Moltke, L., Cox, G.F., Electrocardiographic Evaluation of Eliglustat: Results of a Thorough QT Study and Phase 2 and 3 Clinical Trials [asbtract], European Working Group on Gaucher Disease 11th Meeting, Haifa, Israel. 2014.
27. Hou, A.W., Patel, P., Peterschmitt, M.J., Ibrahim, J., Gaemers, S.J.M., Two-year postmarketing safety experience with oral eliglustat in adults with Gaucher disease type 1 [abstract]. 2017, In press, Mol. Genet. Metab.