Eliglustat

Eliglustat, sold under the brand name Cerdelga, is a medication used for the treatment of Gaucher's disease. It was discovered at the University of Michigan, developed by Genzyme Corp, and was approved by the FDA in August 2014.[3] Commonly used as the tartrate salt, the compound is believed to work by inhibition of glucosylceramide synthase.[4][5] According to an article in Journal of the American Medical Association the oral substrate reduction therapy resulted in "significant improvements in spleen volume, hemoglobin level, liver volume, and platelet count" in untreated adults with Gaucher disease Type 1.[6]

Eliglustat
Clinical data
Trade namesCerdelga
AHFS/Drugs.comMonograph
MedlinePlusa618038
License data
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Identifiers
IUPAC name
  • N-[(1R,2R)-1-(2,3-Dihydro-1,4-benzodioxin-6-yl)-1-hydroxy-3-(1-pyrrolidinyl)-2-propanyl]octanamide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC23H36N2O4
Molar mass404.551 g·mol−1
3D model (JSmol)
SMILES
  • CCCCCCCC(=O)N[C@H](CN1CCCC1)[C@@H](C2=CC3=C(C=C2)OCCO3)O
InChI
  • InChI=1S/C23H36N2O4/c1-2-3-4-5-6-9-22(26)24-19(17-25-12-7-8-13-25)23(27)18-10-11-20-21(16-18)29-15-14-28-20/h10-11,16,19,23,27H,2-9,12-15,17H2,1H3,(H,24,26)/t19-,23-/m1/s1
  • Key:FJZZPCZKBUKGGU-AUSIDOKSSA-N

History

Norman Radin began exploring the possibility of inhibiting the synthesis of lipid substrates involved in Gaucher's disease as early as 1982, and, in collaboration with the laboratory of Jim Shayman, found several candidate inhibitors in the mid-1990s.[7] Genzyme initially rejected the candidates developed by Radin and Shayman, but after a news broke of a competitor developing a new treatment for Gaucher's disease, licensed the Radin/Shayman patents in 2000.[7] Eliglustat did not receive FDA approval for another 14 years, a delay that Shayman speculated was due to some company leaders not being fully committed to developing a drug that would compete with imiglucerase (brand name Cerezyme), Genzyme's flagship treatment for Gaucher's disease.[7]

Society and culture

Economics

In 2014, the annual cost of eliglustat taken orally twice a day was $310,250. Cerezyme cost about $300,000 for the intravenous medication if taken twice a month.[8] Manufacturing costs for eliglustat are slightly lower than for imiglucerase. Genzyme maintains higher prices for orphan drugs—most often paid for by insurers—in order to remain financially sustainable.[8]

References
  1. "Cerdelga 84 mg Hard Capsules - Summary of Product Characteristics (SmPC)". (emc). 8 January 2020. Retrieved 30 January 2021.
  2. "Cerdelga- eliglustat capsule". DailyMed. Retrieved 30 January 2021.
  3. "FDA approves new drug to treat a form of Gaucher disease" (Press release). U.S. Food and Drug Administration. 19 August 2015. Archived from the original on 16 February 2017. Retrieved 18 July 2015.
  4. Lee L, Abe A, Shayman JA (May 1999). "Improved inhibitors of glucosylceramide synthase". The Journal of Biological Chemistry. 274 (21): 14662–9. doi:10.1074/jbc.274.21.14662. PMID 10329660.
  5. Shayman JA (August 2010). "ELIGLUSTAT TARTRATE: Glucosylceramide Synthase Inhibitor Treatment of Type 1 Gaucher Disease". Drugs of the Future. 35 (8): 613–620. doi:10.1358/dof.2010.035.08.1505566. PMC 3340614. PMID 22563139.
  6. Mistry PK, Lukina E, Ben Turkia H, Amato D, Baris H, Dasouki M, et al. (February 2015). "Effect of oral eliglustat on splenomegaly in patients with Gaucher disease type 1: the ENGAGE randomized clinical trial". JAMA. 313 (7): 695–706. doi:10.1001/jama.2015.459. PMC 4962880. PMID 25688781.
  7. Garber K (December 2017), Just Reward, Ann Arbor Observer, retrieved 17 January 2021
  8. Weisman R (2 September 2014), New Genzyme pill will cost patients $310,250 a year, The Boston Globe, retrieved 18 July 2015
  • "Eliglustat". Drug Information Portal. U.S. National Library of Medicine.
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