View in EDS

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.

Saved in:
Bibliographic Details
Title: 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.
Authors: Cox, Timothy M (AUTHOR), Drelichman, Guillermo (AUTHOR), Cravo, Renata (AUTHOR), Balwani, Manisha (AUTHOR), Burrow, Thomas Andrew (AUTHOR), Martins, Ana Maria (AUTHOR), Lukina, Elena (AUTHOR), Rosenbloom, Barry (AUTHOR), Ross, Leorah (AUTHOR), Angell, Jennifer (AUTHOR), Puga, Ana Cristina (AUTHOR)
Source: Lancet. 6/13/2015, Vol. 385 Issue 9985, p2355-2362. 8p.
Abstract: Background: The mainstay of treatment for Gaucher's disease type 1 is alternate-week infusion of enzyme replacement therapy (ERT). We investigated whether patients stable on such treatment would remain so after switching to oral eliglustat, a selective inhibitor of glucosylceramide synthase.Methods: In this phase 3, randomised, multinational, open-label, non-inferiority trial, we enrolled adults (aged ≥18 years) who had received ERT for 3 years or more for Gaucher's disease. Patients were randomly allocated 2:1 at 39 clinics (stratified by ERT dose; block sizes of four; computer-generated centrally) to receive either oral eliglustat or imiglucerase infusions for 12 months. Participants and investigators were aware of treatment assignment, but the central reader who assessed organ volumes was masked. The composite primary efficacy endpoint was percentage of patients whose haematological variables and organ volumes remained stable for 12 months (ie, haemoglobin decrease not more than 15 g/L, platelet count decrease not more than 25%, spleen volume increase not more than 25%, and liver volume increase not more than 20%, in multiples of normal from baseline). The non-inferiority margin was 25% for eliglustat relative to imiglucerase, assessed in all patients who completed 12 months of treatment. This trial is registered with ClinicalTrials.gov, number NCT00943111, and EudraCT, number 2008-005223-28.Findings: Between Sept 15, 2009, and Nov 9, 2011, we randomly allocated 106 (66%) patients to eliglustat and 54 (34%) to imiglucerase. In the per-protocol population, 84 (85%) of 99 patients who completed eliglustat treatment and 44 (94%) of 47 patients who completed imiglucerase treatment met the composite primary endpoint (between-group difference -8·8%; 95% CI -17·6 to 4·2). The lower bound of the 95% CI of -17·6% was within the prespecified threshold for non-inferiority. Dropouts occurred due to palpitations (one patient on eliglustat), myocardial infarction (one patient on eliglustat), and psychotic disorder (one patient on imiglucerase). No deaths occurred. 97 (92%) of 106 patients in the eliglustat group had treatment-emergent adverse events, as did 42 (79%) of 53 in the imiglucerase group (mostly mild or moderate in severity).Interpretation: Oral eliglustat maintained haematological and organ volume stability in adults with Gaucher's disease type 1 already controlled by intravenous ERT and could be a useful therapeutic option.Funding: Genzyme, a Sanofi company. [ABSTRACT FROM AUTHOR]
Copyright of Lancet is the property of Lancet and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
FullText Text:
  Availability: 0
Header DbId: pbh
DbLabel: Psychology and Behavioral Sciences Collection
An: 109806100
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: 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.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Cox%2C+Timothy+M%22">Cox, Timothy M</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Drelichman%2C+Guillermo%22">Drelichman, Guillermo</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Cravo%2C+Renata%22">Cravo, Renata</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Balwani%2C+Manisha%22">Balwani, Manisha</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Burrow%2C+Thomas+Andrew%22">Burrow, Thomas Andrew</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Martins%2C+Ana+Maria%22">Martins, Ana Maria</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Lukina%2C+Elena%22">Lukina, Elena</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Rosenbloom%2C+Barry%22">Rosenbloom, Barry</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ross%2C+Leorah%22">Ross, Leorah</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Angell%2C+Jennifer%22">Angell, Jennifer</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Puga%2C+Ana+Cristina%22">Puga, Ana Cristina</searchLink> (AUTHOR)
– Name: TitleSource
  Label: Source
  Group: Src
  Data: <searchLink fieldCode="JN" term="%22Lancet%22">Lancet</searchLink>. 6/13/2015, Vol. 385 Issue 9985, p2355-2362. 8p.
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: <bold>Background: </bold>The mainstay of treatment for Gaucher's disease type 1 is alternate-week infusion of enzyme replacement therapy (ERT). We investigated whether patients stable on such treatment would remain so after switching to oral eliglustat, a selective inhibitor of glucosylceramide synthase.<bold>Methods: </bold>In this phase 3, randomised, multinational, open-label, non-inferiority trial, we enrolled adults (aged ≥18 years) who had received ERT for 3 years or more for Gaucher's disease. Patients were randomly allocated 2:1 at 39 clinics (stratified by ERT dose; block sizes of four; computer-generated centrally) to receive either oral eliglustat or imiglucerase infusions for 12 months. Participants and investigators were aware of treatment assignment, but the central reader who assessed organ volumes was masked. The composite primary efficacy endpoint was percentage of patients whose haematological variables and organ volumes remained stable for 12 months (ie, haemoglobin decrease not more than 15 g/L, platelet count decrease not more than 25%, spleen volume increase not more than 25%, and liver volume increase not more than 20%, in multiples of normal from baseline). The non-inferiority margin was 25% for eliglustat relative to imiglucerase, assessed in all patients who completed 12 months of treatment. This trial is registered with ClinicalTrials.gov, number NCT00943111, and EudraCT, number 2008-005223-28.<bold>Findings: </bold>Between Sept 15, 2009, and Nov 9, 2011, we randomly allocated 106 (66%) patients to eliglustat and 54 (34%) to imiglucerase. In the per-protocol population, 84 (85%) of 99 patients who completed eliglustat treatment and 44 (94%) of 47 patients who completed imiglucerase treatment met the composite primary endpoint (between-group difference -8·8%; 95% CI -17·6 to 4·2). The lower bound of the 95% CI of -17·6% was within the prespecified threshold for non-inferiority. Dropouts occurred due to palpitations (one patient on eliglustat), myocardial infarction (one patient on eliglustat), and psychotic disorder (one patient on imiglucerase). No deaths occurred. 97 (92%) of 106 patients in the eliglustat group had treatment-emergent adverse events, as did 42 (79%) of 53 in the imiglucerase group (mostly mild or moderate in severity).<bold>Interpretation: </bold>Oral eliglustat maintained haematological and organ volume stability in adults with Gaucher's disease type 1 already controlled by intravenous ERT and could be a useful therapeutic option.<bold>Funding: </bold>Genzyme, a Sanofi company. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Lancet is the property of Lancet and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=109806100
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1016/S0140-6736(14)61841-9
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 8
        StartPage: 2355
    Titles:
      – TitleFull: 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.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Cox, Timothy M
      – PersonEntity:
          Name:
            NameFull: Drelichman, Guillermo
      – PersonEntity:
          Name:
            NameFull: Cravo, Renata
      – PersonEntity:
          Name:
            NameFull: Balwani, Manisha
      – PersonEntity:
          Name:
            NameFull: Burrow, Thomas Andrew
      – PersonEntity:
          Name:
            NameFull: Martins, Ana Maria
      – PersonEntity:
          Name:
            NameFull: Lukina, Elena
      – PersonEntity:
          Name:
            NameFull: Rosenbloom, Barry
      – PersonEntity:
          Name:
            NameFull: Ross, Leorah
      – PersonEntity:
          Name:
            NameFull: Angell, Jennifer
      – PersonEntity:
          Name:
            NameFull: Puga, Ana Cristina
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 13
              M: 06
              Text: 6/13/2015
              Type: published
              Y: 2015
          Identifiers:
            – Type: issn-print
              Value: 01406736
          Numbering:
            – Type: volume
              Value: 385
            – Type: issue
              Value: 9985
          Titles:
            – TitleFull: Lancet
              Type: main
ResultId 1