OVERVIEW

PRODUCT INFORMATION

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NO.	MOLECULAR FORMULA	STRUCTURE
Eliglustat	491833-29-5	C23-H36-N2-O4

ANNOTATED BIBLIOGRAPHY

References updated: 05 March 2018

• Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman’s the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 397-416.

  (Textbook of pharmacology and therapeutics; eliglustat is not discussed).
• McEachern KA, Fung J, Komarnitsky S, Siegel CS, Chuang WL, Hutto E, Shayman JA, et al. A specific and potent inhibitor of glucosylceramide synthase for substrate inhibition therapy of Gaucher disease. Mol Genet Metab 2007; 91: 259-67. [PubMed: 17509920]

  (Description of a novel glucosylceramide synthase inhibitor [Genz-112738: eliglustat] that inhibits the intracellular enzyme in normal cells, and decreases glucosylceramide accumulation in cells of mouse models of Gaucher disease with no appreciable toxicity providing a substrate inhibition approach to therapy).
• Lukina E, Watman N, Arreguin EA, Dragosky M, Iastrebner M, Rosenbaum H, Phillips M, 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: 4095-8. [PMC free article: PMC2993616] [PubMed: 20713962]

  (Among 20 adults with type 1 Gaucher disease treated with eliglustat for at least 2 years, there were clinically important improvements in hemoglobin and platelet count and decreases in spleen and liver size with minimal side effects; no mention of ALT elevations or hepatotoxicity).
• Lukina E, Watman N, Dragosky M, Pastores GM, Arreguin EA, Rosenbaum H, Zimran A, 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: 274-6. [PubMed: 24835462]

  (Among 26 patients with type 1 Gaucher disease treated with eliglustat for up to 4 years, clinical improvements were maintained and there were increasing improvements in bone density; adverse events were largely unrelated to therapy; no mention of ALT elevations or hepatotoxicity).
• Eliglustat (Cerdelga)--an oral drug for Gaucher disease. Med Lett Drugs Ther 2015; 57 (1472): e100-1. [PubMed: 26147895]

  (Concise review of the mechanism of action, clinical efficacy, safety, drug-drug interactions and costs of eliglustat shortly after its approval in the US, mentions side effects of fatigue, headache, nausea, diarrhea and back pain, but does not mention ALT elevations or hepatotoxicity).
• Mistry PK, Lukina E, Ben Turkia H, Amato D, Baris H, Dasouki M, Ghosn M, 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. [PMC free article: PMC4962880] [PubMed: 25688781]

  (Among 40 patients with type 1 Gaucher disease treated with eliglustat or placebo for 9 months, hemoglobin and platelet counts increased and liver and spleen size decreased on eliglustat, but not on placebo and there were no severe adverse events attributable to therapy; no mention of ALT elevations or hepatotoxicity).
• Cox TM, Drelichman G, Cravo R, Balwani M, Burrow TA, Martins AM, Lukina E, 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 (9985): 2355-62. [PubMed: 25819691]

  (Among 106 patients with stable type 1 Gaucher disease on long term enzyme replacement therapy who were switched to eliglustat or maintained on imiglucerase for 12 months, clinical features were stable in both groups, while side effects more frequent with eliglustat included diarrhea, fatigue, nausea, headache, dyspepsia and abdominal pain; no mention of ALT elevations or hepatotoxicity, but one patient developed hepatocellular carcinoma).
• Mistry PK, Lukina E, Ben Turkia H, Shankar SP, Baris H, Ghosn M, Mehta A, et al. Outcomes after 18 months of eliglustat therapy in treatment-naïve adults with Gaucher disease type 1: The phase 3 ENGAGE trial. Am J Hematol 2017; 92: 1170-6. [PMC free article: PMC5656936] [PubMed: 28762527]

  (Among 40 patients with Gaucher disease treated with eliglustat or placebo for 9 months, spleen size decreased [-28% vs +3%] and platelet counts increased [+32% vs -9%], while there were no serious adverse events in either group and no "clinically meaningful worsening" of routine laboratory test results).
• Cox TM, Drelichman G, Cravo R, Balwani M, Burrow TA, Martins AM, Lukina E, et al. Eliglustat maintains long-term clinical stability in patients with Gaucher disease type 1 stabilized on enzyme therapy. Blood 2017; 129: 2375-83. [PMC free article: PMC5409450] [PubMed: 28167660]

  (Among 157 patients with Gaucher diseae who were enrolled in a long term extension study after a one year controlled trial of eliglustat vs imiglucerase [Cox 2015], liver and spleen size, hemoglobin and platelet counts were stable for 1-4 years of therapy and there were no serious adverse events or drug discontinuations for ALT elevations or acute hepatotoxicity).
• Peterschmitt MJ, Cox GF, Ibrahim J, MacDougall J, Underhill LH, Patel P, Gaemers SJM. 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 2018; 68: 185-91. [PubMed: 28126395]

  (Among 393 patients with Gaucher disease treated with eliglustat in 4 clinical trials, there were no serious adverse events or drug discontinuations because of ALT elevations or acute liver injury).
• Charrow J, Fraga C, Gu X, Ida H, Longo N, Lukina E, Nonino A, Gaemers SJM, Jouvin MH, Li J, Wu Y, Xue Y, Peterschmitt MJ. Once- versus twice-daily dosing of eliglustat in adults with Gaucher disease type 1: The Phase 3, randomized, double-blind EDGE trial. Mol Genet Metab 2018; 123: 347-56. [PubMed: 29358012]

  (Among 170 adults with Gaucher disease treated with once or twice daily eliglustat for a median of 3.3 years, all deaths [n=2] were unrelated and there were no liver related severe adverse events or liver adverse event related discontinuations).
• Zimran A, Belmatoug N, Bembi B, Deegan P, Elstein D, Fernandez-Sasso D, Giraldo P, et al.; GOS Study group. Demographics and patient characteristics of 1209 patients with Gaucher disease: Descriptive analysis from the Gaucher Outcome Survey (GOS). Am J Hematol 2018; 93: 205-12. [PMC free article: PMC5814927] [PubMed: 29090476]

  (Summary of clinical features of 1209 patients [95% type 1] enrolled in an international Gaucher disease registry between 2010 and 2017, including 887 [73%] who received at least one therapy, most commonly imiglucerase [66%], velaglucerase [57%], alglucerase [12%], taliglucerase [10%] and miglustat [10%], does not mention eliglustat, adverse events or liver related complications of treatment).