Real-Life Experience with Oral Eliglustat in Patients with Gaucher Disease Previously Treated with Enzyme Replacement Therapy

Overview

Journal J Clin Med

Specialty General Medicine

Date 2022 Nov 11

PMID 36362492

Authors

Majdolen Istaiti

Michal Becker-Cohen

Tama Dinur

Shoshana Revel-Vilk

Ari Zimran

Affiliations

Soon will be listed here.

Abstract

Three types of enzyme replacement therapies (ERTs) and two substrate reduction therapies (SRTs) are approved for symptomatic patients with type 1 Gaucher disease (GD1). Eliglustat is the second SRT approved, yet the first to be approved as first-line therapy for any adult patients with compatible CYP2D6 metabolizer genotype. Herein we report safety and efficacy data of the first 29 patients switched from ERT to eliglustat from the Gaucher Unit at Shaare Zedek Medical Center (SZMC) between 07/2017 and 06/2022; the median (range) time on ERT was 13 (0.66-30) years, and the median (range) time on eliglustat was 7 (1-52) months. Most patients switched due to oral preference or sub-optimal response to low-dose ERT. Twelve patients stopped eliglustat after a median (range) of 4 (1-18) months; 11 due to adverse events (AEs) and one due to personal request. There were no drug-related serious AEs and no drug-related cardiac events. Most AEs were mild and transient, mainly dyspepsia. Efficacy achievements were reflected by maintaining stability. We concluded that switching from ERT to eliglustat is safe if choosing the appropriate patients. Reassuring patients to tolerate early AEs may reduce discontinuation. Following the response and compliance to therapy is important to ensure long-term efficacy.

Citing Articles

Exploration of phytoconstituents of Medhya Rasayana herbs to identify potential inhibitors for through high-throughput screening.

Singh N, Singh A Front Mol Biosci. 2024; 11:1476482.

PMID: 39450315 PMC: 11500077. DOI: 10.3389/fmolb.2024.1476482.

Screening of phytoconstituents from Bacopa monnieri (L.) Pennell and Mucuna pruriens (L.) DC. to identify potential inhibitors against Cerebroside sulfotransferase.

Singh N, Singh A PLoS One. 2024; 19(10):e0307374.

PMID: 39446901 PMC: 11500956. DOI: 10.1371/journal.pone.0307374.

Phytoconstituents of Withania somnifera (L.) Dunal (Ashwagandha) unveiled potential cerebroside sulfotransferase inhibitors: insight through virtual screening, molecular dynamics, toxicity, and reverse pharmacophore analysis.

Singh N, Singh A J Biol Eng. 2024; 18(1):59.

PMID: 39444022 PMC: 11515467. DOI: 10.1186/s13036-024-00456-x.

Real life data: follow-up assessment on Spanish Gaucher disease patients treated with eliglustat. TRAZELGA project.

Serrano-Gonzalo I, Lopez de Frutos L, Lahoz-Gil C, Delgado-Mateos F, Fernandez-Galan M, Morales-Conejo M Orphanet J Rare Dis. 2023; 18(1):390.

PMID: 38102667 PMC: 10722815. DOI: 10.1186/s13023-023-02939-4.

References

Revel-Vilk S, Szer J, Mehta A, Zimran A . How we manage Gaucher Disease in the era of choices. Br J Haematol. 2018; 182(4):467-480. DOI: 10.1111/bjh.15402. View

Wagner V, Northrup H, Hashmi S, Nguyen J, Koenig M, Davis J . Attitudes of Individuals with Gaucher Disease toward Substrate Reduction Therapies. J Genet Couns. 2017; 27(1):169-176. PMC: 5794801. DOI: 10.1007/s10897-017-0137-0. View

Elstein D, Dweck A, Attias D, Hadas-Halpern I, Zevin S, Altarescu G . Oral maintenance clinical trial with miglustat for type I Gaucher disease: switch from or combination with intravenous enzyme replacement. Blood. 2007; 110(7):2296-301. DOI: 10.1182/blood-2007-02-075960. View

Mistry P, Balwani M, Baris H, Ben Turkia H, Burrow T, Charrow J . Safety, efficacy, and authorization of eliglustat as a first-line therapy in Gaucher disease type 1. Blood Cells Mol Dis. 2018; 71:71-74. DOI: 10.1016/j.bcmd.2018.04.001. View

Sagara R, Ishigaki M, Otsuka M, Murayama K, Ida H, Fernandez J . Long-term safety and effectiveness of velaglucerase alfa in Gaucher disease: 6-year interim analysis of a post-marketing surveillance in Japan. Orphanet J Rare Dis. 2021; 16(1):502. PMC: 8642863. DOI: 10.1186/s13023-021-02119-2. View

Zimran A, Goldblatt J, Szer J . Should eliglustat be first line therapy for patients with type 1 Gaucher disease? Definitions of safety and efficacy. Blood Cells Mol Dis. 2017; 68:14-16. DOI: 10.1016/j.bcmd.2017.09.003. View

Mistry P, Balwani M, Charrow J, Kishnani P, Niederau C, Underhill L . Real-world effectiveness of eliglustat in treatment-naïve and switch patients enrolled in the International Collaborative Gaucher Group Gaucher Registry. Am J Hematol. 2020; 95(9):1038-1046. PMC: 7497238. DOI: 10.1002/ajh.25875. View

Serratrice C, Swiader L, Serratrice J . Switching from imiglucerase to miglustat for the treatment of French patients with Gaucher disease type 1: a case series. J Med Case Rep. 2015; 9:146. PMC: 4488047. DOI: 10.1186/s13256-015-0617-5. View

Pastores G, Petakov M, Giraldo P, Rosenbaum H, Szer J, Deegan P . A Phase 3, multicenter, open-label, switchover trial to assess the safety and efficacy of taliglucerase alfa, a plant cell-expressed recombinant human glucocerebrosidase, in adult and pediatric patients with Gaucher disease previously treated with.... Blood Cells Mol Dis. 2014; 53(4):253-60. DOI: 10.1016/j.bcmd.2014.05.004. View

10.

Kleytman N, Ruan J, Ruan A, Zhang B, Murugesan V, Lin H . Incremental biomarker and clinical outcomes after switch from enzyme therapy to eliglustat substrate reduction therapy in Gaucher disease. Mol Genet Metab Rep. 2021; 29:100798. PMC: 8408524. DOI: 10.1016/j.ymgmr.2021.100798. View

11.

Peterschmitt M, Freisens S, Underhill L, Foster M, Lewis G, Gaemers S . Long-term adverse event profile from four completed trials of oral eliglustat in adults with Gaucher disease type 1. Orphanet J Rare Dis. 2019; 14(1):128. PMC: 6555985. DOI: 10.1186/s13023-019-1085-6. View

12.

Stein P, Malhotra A, Haims A, Pastores G, Mistry P . Focal splenic lesions in type I Gaucher disease are associated with poor platelet and splenic response to macrophage-targeted enzyme replacement therapy. J Inherit Metab Dis. 2010; 33(6):769-74. PMC: 3008694. DOI: 10.1007/s10545-010-9175-6. View

13.

Belmatoug N, Di Rocco M, Fraga C, Giraldo P, Hughes D, Lukina E . Management and monitoring recommendations for the use of eliglustat in adults with type 1 Gaucher disease in Europe. Eur J Intern Med. 2016; 37:25-32. DOI: 10.1016/j.ejim.2016.07.011. View

14.

Elstein D, Mehta A, Hughes D, Giraldo P, Charrow J, Smith L . Safety and efficacy results of switch from imiglucerase to velaglucerase alfa treatment in patients with type 1 Gaucher disease. Am J Hematol. 2015; 90(7):592-7. DOI: 10.1002/ajh.24007. View

15.

Deegan P, Cox T . Imiglucerase in the treatment of Gaucher disease: a history and perspective. Drug Des Devel Ther. 2012; 6:81-106. PMC: 3340106. DOI: 10.2147/DDDT.S14395. View

16.

Dinur T, Bauer P, Beetz C, Kramp G, Cozma C, Iurascu M . Gaucher Disease Diagnosis Using Lyso-Gb1 on Dry Blood Spot Samples: Time to Change the Paradigm?. Int J Mol Sci. 2022; 23(3). PMC: 8835963. DOI: 10.3390/ijms23031627. View

17.

Nabizadeh A, Amani B, Kadivar M, Toroski M, Abdollahi Asl A, Bayazidi Y . The Clinical Efficacy of Imiglucerase versus Eliglustat in Patients with Gaucher's Disease Type 1: A Systematic Review. J Res Pharm Pract. 2019; 7(4):171-177. PMC: 6298139. DOI: 10.4103/jrpp.JRPP_18_24. View

18.

Canda E, Kose M, Kagnici M, Ucar S, Sozmen E, Coker M . Patients with Gaucher type 1: Switching from imiglucerase to miglustat therapy. Blood Cells Mol Dis. 2017; 68:180-184. DOI: 10.1016/j.bcmd.2017.01.007. View

19.

van Dussen L, Cox T, Hendriks E, Morris E, Akkerman E, Maas M . Effects of switching from a reduced dose imiglucerase to velaglucerase in type 1 Gaucher disease: clinical and biochemical outcomes. Haematologica. 2012; 97(12):1850-4. PMC: 3590092. DOI: 10.3324/haematol.2011.059071. View