Eliglustat: A Review in Gaucher Disease Type 1

@article{Scott2015EliglustatAR,
  title={Eliglustat: A Review in Gaucher Disease Type 1},
  author={Lesley J. Scott},
  journal={Drugs},
  year={2015},
  volume={75},
  pages={1669-1678}
}
  • L. Scott
  • Published 18 September 2015
  • Medicine
  • Drugs
Oral eliglustat (Cerdelga®) is approved in several countries for the long-term treatment of adults with Gaucher disease type 1 (GD1) who are cytochrome P450 (CYP) 2D6 extensive metabolizers (EMs), intermediate metabolizer (IMs) or poor metabolizers (PMs) [these three CYP categories encompass >90 % of individuals]. Eliglustat is a potent, selective inhibitor of glucosylceramide synthase, the rate-limiting enzyme in the synthesis of certain glycosphingolipids, and thus, reduces the rate of… 
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28 Citations

Recommendations for oral treatment for adult patients with type 1 Gaucher disease.

Recomendaciones para el tratamiento oral de pacientes adultos con enfermedad de Gaucher tipo 1

Suicidal attempt with eliglustat overdose

A 29‐year‐old female with GD1, a poor metabolizer of cytochrome P450 2D6 on a recommended daily dose of 84 mg of elig Lustat, had taken 94 capsules of eliglustat and suffered from somnolence, severe bradycardia, and hypotension one hour after ingestion.

Glucosylsphingosine (Lyso-Gb1): An Informative Biomarker in the Clinical Monitoring of Patients with Gaucher Disease

Clinical vignettes highlight the role of lyso-Gb1 as a sensitive biomarker in management of patients with GD, and its further value when CHITO is normal and thus uninformative, and the personalized medicine approach needed to optimize treatment outcomes.

Choroba Gauchera – zalecenia dotyczące rozpoznawania, leczenia i monitorowania

Drug–Drug Interactions Of Amiodarone And Quinidine On The Pharmacokinetics Of Eliglustat In Rats

Amiodarone and quinidine can elevate eliglustat exposure and have an inhibitory effect on eliglustats metabolism and appropriate pharmacological studies of eliglust at in patients treated with amiodar one or quinine should be done in future.

Mucopolysaccharidosis type III: current clinical trials, challenges and recommendations

As early initiation of treatment is needed to demonstrate maximal, or even sufficient, treatment effect, newborn screening for MPS III will, in the end, be needed.

Brain Penetrable Inhibitors of Ceramide Galactosyltransferase for the Treatment of Lysosomal Storage Disorders.

Sub substrate reduction therapy (SRT) was proposed as a novel approach to treat this disease, by inhibiting ceramide galactosyltransferase enzyme (UGT8), which showed efficacy in the in vivo pharmacodynamic models, indicating the potential to treat MLD with UGT8 inhibitors.

Lucerastat, an iminosugar with potential as substrate reduction therapy for glycolipid storage disorders: safety, tolerability, and pharmacokinetics in healthy subjects

The safety, tolerability, and pharmacokinetics of oral lucerastat were evaluated in two separate randomized, double-blind, placebo-controlled, single- and multiple-ascending dose studies (SAD and MAD, respectively) in healthy male subjects and the results warrant further investigation of substrate reduction therapy in patients with glycolipid storage disorders.

N-butyldeoxynojirimycin (miglustat) ameliorates pulmonary fibrosis through inhibition of nuclear translocation of Smad2/3.

References

SHOWING 1-10 OF 25 REFERENCES

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

ELIGLUSTAT TARTRATE: Glucosylceramide Synthase Inhibitor Treatment of Type 1 Gaucher Disease.

  • J. Shayman
  • Biology, Chemistry
    Drugs of the future
  • 2010
Pre-clinical pharmacological studies demonstrate that the agent has a high therapeutic index, excellent oral bioavailability and limited toxicity, and two randomized phase III trials testing the efficacy and safety of eliglustat tartrate are currently in progress.

ELIGLUSTAT TARTRATE: Glucosylceramide Synthase Inhibitor Treatment of Type 1 Gaucher Disease.

Pre-clinical pharmacological studies demonstrate that the agent has a high therapeutic index, excellent oral bioavailability and limited toxicity, and two randomized phase III trials testing the efficacy and safety of eliglustat tartrate are currently in progress.

A phase 2 study of eliglustat tartrate (Genz-112638), an oral substrate reduction therapy for Gaucher disease type 1.

Eliglustat tartrate appears to be a promising oral treatment for Gaucher disease type 1, and 7 mild, transient adverse events in 6 patients were considered treatment-related.

Effect of oral eliglustat on splenomegaly in patients with Gaucher disease type 1: the ENGAGE randomized clinical trial.

Among previously untreated adults with Gaucher disease type 1, treatment with eliglustat compared with placebo for 9 months resulted in significant improvements in spleen volume, hemoglobin level, liver volume, and platelet count.

Skeletal improvement in patients with Gaucher disease type 1: a phase 2 trial of oral eliglustat

Eliglustat may be a therapeutic option for treating the skeletal manifestations of Gaucher disease type 1 and its skeletal effects were evaluated by prospective monitoring of bone mineral density, fractures, marrow infiltration by Gaucher cells, focal bone lesions, and infarcts during an open-label, multi-site, single-arm phase 2 trial.

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.

Improvements after 2 years of treatment in patients with baseline splenomegaly and thrombocytopenia and/or anemia are reported, with major gains in osteoporotic and osteopenic patients.

ENCORE, a randomized, controlled, open-label non-inferiority study comparing eliglustat to imiglucerase in Gaucher disease type 1 patients stabilized on enzyme replacement therapy: 24-month results

Improved management of lysosomal glucosylceramide levels in a mouse model of type 1 Gaucher disease using enzyme and substrate reduction therapy

In patients whose disease has been stabilized by intravenously administered recombinant glucocerebrosidase, orally administered SRT with Genz-112638 could potentially be used as a convenient maintenance therapy, in patients naïve to treatment, ERT followed by SRT could potentially accelerate clearance of the offending substrate.

Therapeutic goals in the treatment of Gaucher disease.

Gaucher disease, the most common lysosomal storage disorder, is a heterogeneous multisystem condition and an evidence-based consensus on contemporary therapeutic goals is obtained to arrive at a comprehensive guide to individualized management.