LONG-TERM HEMATOLOGIC, BIOMARKER, AND BONE RESPONSE TO ORAL ELIGLUSTAT IN PATIENTS WITH GAUCHER DISEASE TYPE 1: RESULTS FROM A PHASE 2 AND TWO PHASE 3 TRIALS
(Abstract release date: 05/19/16)
EHA Library. Lukina E. 06/11/16; 135275; S519
Prof. Dr. Elena Lukina
Contributions
Contributions
Abstract
Abstract: S519
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:45 - 17:00
Location: Room H4
Background
Gaucher disease is caused by deficient activity of lysosomal acid β-glucosidase, leading to glucosylceramide accumulation in macrophages and resultant hepatosplenomegaly, pancytopenia, and skeletal disease. Despite well-characterized symptoms and treatment availability, disease awareness is low. Diagnostic delays are common and can result in irreversible disease manifestations. As thrombocytopenia, anemia, and splenomegaly are common in Gaucher patients, hematologists often identify, evaluate, and manage the disease. Eliglustat, a substrate reduction therapy, is a first-line oral treatment for adults with Gaucher disease type 1 (GD1) who have a compatible CYP2D6 metabolizer phenotype (>90% of patients).
Aims
Summarize hematologic, bone, and Gaucher biomarker outcomes (chitotriosidase and others) in 3 clinical trials of eliglustat in adults with GD1.
Methods
Data were evaluated from 3 Sanofi Genzyme-sponsored trials: Phase 2 in treatment-naïve patients (NCT00358150, N=26); ENGAGE, a randomized, placebo-controlled Phase 3 trial in treatment-naïve patients (NCT00891202, N=40); and ENCORE, a Phase 3 imiglucerase-controlled trial in patients previously stabilized on ≥3 years of enzyme replacement therapy (NCT00943111, N=159).
Results
Primary endpoints were met in all 3 trials (Lukina Blood 2010; Mistry JAMA 2015; Cox Lancet 2015). In the Phase 2 study after 4 years, mean hemoglobin increased by 2.3±1.5 g/dL relative to baseline (BL) (BL=11.3±1.5 g/dL), mean platelet count increased by 95% (BL=69±21x109/L), spleen and liver volumes decreased, and mean lumbar spine bone mineral density went from the osteopenic to the normal range with corresponding reductions in biomarkers. In ENGAGE after 18 months, mean hemoglobin levels, platelet counts and spleen and liver volumes improved in placebo patients switched to eliglustat and continued to improve in patients continuing on eliglustat, with corresponding improvements in mean bone marrow burden (BMB) score and biomarkers. In former placebo patients, mean hemoglobin increased by 0.79±0.82 g/dL (BL=12.2±2.0 g/dL), mean platelet count increased by 40%±37 (BL=71.5±25.2 x109/L) and mean BMB score decreased by 0.9 after 9 months on eliglustat. In patients on eliglustat for 18 months, mean hemoglobin increased by 1.02±0.84 g/dL (BL=12.1±1.8 g/dL), mean platelet count increased by 58%±41 (BL=75±14x109/L), and mean BMB score decreased by 2.2. In ENCORE after 2 years, stability with respect to hemoglobin, platelets, spleen, liver, bone, and biomarkers was maintained in former imiglucerase patients switching to eliglustat and in patients continuing on eliglustat. In former imiglucerase patients, 100% maintained stable hemoglobin (mean change: 0.04±0.78 g/dL) and 90% maintained stable platelets after 1 year of eliglustat (mean change: ‑1.46±31.7x109/L). In patients continuing on eliglustat, 97% maintained stable hemoglobin (mean change: ‑0.10±0.77 g/dL) and 94% maintained stable platelets (mean change: 2.27±17.6x109/L) after 2 years. Mean bone values, all in the normal range at baseline, remained normal after 1–2 years of eliglustat. In all 3 trials, eliglustat was generally well tolerated; 90% of patients overall elected to continue on eliglustat. Most adverse events were non-serious, considered unrelated to eliglustat, and mild or moderate in severity.
Conclusion
Long-term use of eliglustat in adults with GD1 was associated with continued improvements in clinical parameters in previously untreated patients and clinical stability in patients previously stabilized on enzyme replacement therapy.
Session topic: Platelet disorders 1
Keyword(s): Gaucher disease, Lysosomal storage disease, Outcome, Treatment
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:45 - 17:00
Location: Room H4
Background
Gaucher disease is caused by deficient activity of lysosomal acid β-glucosidase, leading to glucosylceramide accumulation in macrophages and resultant hepatosplenomegaly, pancytopenia, and skeletal disease. Despite well-characterized symptoms and treatment availability, disease awareness is low. Diagnostic delays are common and can result in irreversible disease manifestations. As thrombocytopenia, anemia, and splenomegaly are common in Gaucher patients, hematologists often identify, evaluate, and manage the disease. Eliglustat, a substrate reduction therapy, is a first-line oral treatment for adults with Gaucher disease type 1 (GD1) who have a compatible CYP2D6 metabolizer phenotype (>90% of patients).
Aims
Summarize hematologic, bone, and Gaucher biomarker outcomes (chitotriosidase and others) in 3 clinical trials of eliglustat in adults with GD1.
Methods
Data were evaluated from 3 Sanofi Genzyme-sponsored trials: Phase 2 in treatment-naïve patients (NCT00358150, N=26); ENGAGE, a randomized, placebo-controlled Phase 3 trial in treatment-naïve patients (NCT00891202, N=40); and ENCORE, a Phase 3 imiglucerase-controlled trial in patients previously stabilized on ≥3 years of enzyme replacement therapy (NCT00943111, N=159).
Results
Primary endpoints were met in all 3 trials (Lukina Blood 2010; Mistry JAMA 2015; Cox Lancet 2015). In the Phase 2 study after 4 years, mean hemoglobin increased by 2.3±1.5 g/dL relative to baseline (BL) (BL=11.3±1.5 g/dL), mean platelet count increased by 95% (BL=69±21x109/L), spleen and liver volumes decreased, and mean lumbar spine bone mineral density went from the osteopenic to the normal range with corresponding reductions in biomarkers. In ENGAGE after 18 months, mean hemoglobin levels, platelet counts and spleen and liver volumes improved in placebo patients switched to eliglustat and continued to improve in patients continuing on eliglustat, with corresponding improvements in mean bone marrow burden (BMB) score and biomarkers. In former placebo patients, mean hemoglobin increased by 0.79±0.82 g/dL (BL=12.2±2.0 g/dL), mean platelet count increased by 40%±37 (BL=71.5±25.2 x109/L) and mean BMB score decreased by 0.9 after 9 months on eliglustat. In patients on eliglustat for 18 months, mean hemoglobin increased by 1.02±0.84 g/dL (BL=12.1±1.8 g/dL), mean platelet count increased by 58%±41 (BL=75±14x109/L), and mean BMB score decreased by 2.2. In ENCORE after 2 years, stability with respect to hemoglobin, platelets, spleen, liver, bone, and biomarkers was maintained in former imiglucerase patients switching to eliglustat and in patients continuing on eliglustat. In former imiglucerase patients, 100% maintained stable hemoglobin (mean change: 0.04±0.78 g/dL) and 90% maintained stable platelets after 1 year of eliglustat (mean change: ‑1.46±31.7x109/L). In patients continuing on eliglustat, 97% maintained stable hemoglobin (mean change: ‑0.10±0.77 g/dL) and 94% maintained stable platelets (mean change: 2.27±17.6x109/L) after 2 years. Mean bone values, all in the normal range at baseline, remained normal after 1–2 years of eliglustat. In all 3 trials, eliglustat was generally well tolerated; 90% of patients overall elected to continue on eliglustat. Most adverse events were non-serious, considered unrelated to eliglustat, and mild or moderate in severity.
Conclusion
Long-term use of eliglustat in adults with GD1 was associated with continued improvements in clinical parameters in previously untreated patients and clinical stability in patients previously stabilized on enzyme replacement therapy.
Session topic: Platelet disorders 1
Keyword(s): Gaucher disease, Lysosomal storage disease, Outcome, Treatment
Abstract: S519
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:45 - 17:00
Location: Room H4
Background
Gaucher disease is caused by deficient activity of lysosomal acid β-glucosidase, leading to glucosylceramide accumulation in macrophages and resultant hepatosplenomegaly, pancytopenia, and skeletal disease. Despite well-characterized symptoms and treatment availability, disease awareness is low. Diagnostic delays are common and can result in irreversible disease manifestations. As thrombocytopenia, anemia, and splenomegaly are common in Gaucher patients, hematologists often identify, evaluate, and manage the disease. Eliglustat, a substrate reduction therapy, is a first-line oral treatment for adults with Gaucher disease type 1 (GD1) who have a compatible CYP2D6 metabolizer phenotype (>90% of patients).
Aims
Summarize hematologic, bone, and Gaucher biomarker outcomes (chitotriosidase and others) in 3 clinical trials of eliglustat in adults with GD1.
Methods
Data were evaluated from 3 Sanofi Genzyme-sponsored trials: Phase 2 in treatment-naïve patients (NCT00358150, N=26); ENGAGE, a randomized, placebo-controlled Phase 3 trial in treatment-naïve patients (NCT00891202, N=40); and ENCORE, a Phase 3 imiglucerase-controlled trial in patients previously stabilized on ≥3 years of enzyme replacement therapy (NCT00943111, N=159).
Results
Primary endpoints were met in all 3 trials (Lukina Blood 2010; Mistry JAMA 2015; Cox Lancet 2015). In the Phase 2 study after 4 years, mean hemoglobin increased by 2.3±1.5 g/dL relative to baseline (BL) (BL=11.3±1.5 g/dL), mean platelet count increased by 95% (BL=69±21x109/L), spleen and liver volumes decreased, and mean lumbar spine bone mineral density went from the osteopenic to the normal range with corresponding reductions in biomarkers. In ENGAGE after 18 months, mean hemoglobin levels, platelet counts and spleen and liver volumes improved in placebo patients switched to eliglustat and continued to improve in patients continuing on eliglustat, with corresponding improvements in mean bone marrow burden (BMB) score and biomarkers. In former placebo patients, mean hemoglobin increased by 0.79±0.82 g/dL (BL=12.2±2.0 g/dL), mean platelet count increased by 40%±37 (BL=71.5±25.2 x109/L) and mean BMB score decreased by 0.9 after 9 months on eliglustat. In patients on eliglustat for 18 months, mean hemoglobin increased by 1.02±0.84 g/dL (BL=12.1±1.8 g/dL), mean platelet count increased by 58%±41 (BL=75±14x109/L), and mean BMB score decreased by 2.2. In ENCORE after 2 years, stability with respect to hemoglobin, platelets, spleen, liver, bone, and biomarkers was maintained in former imiglucerase patients switching to eliglustat and in patients continuing on eliglustat. In former imiglucerase patients, 100% maintained stable hemoglobin (mean change: 0.04±0.78 g/dL) and 90% maintained stable platelets after 1 year of eliglustat (mean change: ‑1.46±31.7x109/L). In patients continuing on eliglustat, 97% maintained stable hemoglobin (mean change: ‑0.10±0.77 g/dL) and 94% maintained stable platelets (mean change: 2.27±17.6x109/L) after 2 years. Mean bone values, all in the normal range at baseline, remained normal after 1–2 years of eliglustat. In all 3 trials, eliglustat was generally well tolerated; 90% of patients overall elected to continue on eliglustat. Most adverse events were non-serious, considered unrelated to eliglustat, and mild or moderate in severity.
Conclusion
Long-term use of eliglustat in adults with GD1 was associated with continued improvements in clinical parameters in previously untreated patients and clinical stability in patients previously stabilized on enzyme replacement therapy.
Session topic: Platelet disorders 1
Keyword(s): Gaucher disease, Lysosomal storage disease, Outcome, Treatment
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:45 - 17:00
Location: Room H4
Background
Gaucher disease is caused by deficient activity of lysosomal acid β-glucosidase, leading to glucosylceramide accumulation in macrophages and resultant hepatosplenomegaly, pancytopenia, and skeletal disease. Despite well-characterized symptoms and treatment availability, disease awareness is low. Diagnostic delays are common and can result in irreversible disease manifestations. As thrombocytopenia, anemia, and splenomegaly are common in Gaucher patients, hematologists often identify, evaluate, and manage the disease. Eliglustat, a substrate reduction therapy, is a first-line oral treatment for adults with Gaucher disease type 1 (GD1) who have a compatible CYP2D6 metabolizer phenotype (>90% of patients).
Aims
Summarize hematologic, bone, and Gaucher biomarker outcomes (chitotriosidase and others) in 3 clinical trials of eliglustat in adults with GD1.
Methods
Data were evaluated from 3 Sanofi Genzyme-sponsored trials: Phase 2 in treatment-naïve patients (NCT00358150, N=26); ENGAGE, a randomized, placebo-controlled Phase 3 trial in treatment-naïve patients (NCT00891202, N=40); and ENCORE, a Phase 3 imiglucerase-controlled trial in patients previously stabilized on ≥3 years of enzyme replacement therapy (NCT00943111, N=159).
Results
Primary endpoints were met in all 3 trials (Lukina Blood 2010; Mistry JAMA 2015; Cox Lancet 2015). In the Phase 2 study after 4 years, mean hemoglobin increased by 2.3±1.5 g/dL relative to baseline (BL) (BL=11.3±1.5 g/dL), mean platelet count increased by 95% (BL=69±21x109/L), spleen and liver volumes decreased, and mean lumbar spine bone mineral density went from the osteopenic to the normal range with corresponding reductions in biomarkers. In ENGAGE after 18 months, mean hemoglobin levels, platelet counts and spleen and liver volumes improved in placebo patients switched to eliglustat and continued to improve in patients continuing on eliglustat, with corresponding improvements in mean bone marrow burden (BMB) score and biomarkers. In former placebo patients, mean hemoglobin increased by 0.79±0.82 g/dL (BL=12.2±2.0 g/dL), mean platelet count increased by 40%±37 (BL=71.5±25.2 x109/L) and mean BMB score decreased by 0.9 after 9 months on eliglustat. In patients on eliglustat for 18 months, mean hemoglobin increased by 1.02±0.84 g/dL (BL=12.1±1.8 g/dL), mean platelet count increased by 58%±41 (BL=75±14x109/L), and mean BMB score decreased by 2.2. In ENCORE after 2 years, stability with respect to hemoglobin, platelets, spleen, liver, bone, and biomarkers was maintained in former imiglucerase patients switching to eliglustat and in patients continuing on eliglustat. In former imiglucerase patients, 100% maintained stable hemoglobin (mean change: 0.04±0.78 g/dL) and 90% maintained stable platelets after 1 year of eliglustat (mean change: ‑1.46±31.7x109/L). In patients continuing on eliglustat, 97% maintained stable hemoglobin (mean change: ‑0.10±0.77 g/dL) and 94% maintained stable platelets (mean change: 2.27±17.6x109/L) after 2 years. Mean bone values, all in the normal range at baseline, remained normal after 1–2 years of eliglustat. In all 3 trials, eliglustat was generally well tolerated; 90% of patients overall elected to continue on eliglustat. Most adverse events were non-serious, considered unrelated to eliglustat, and mild or moderate in severity.
Conclusion
Long-term use of eliglustat in adults with GD1 was associated with continued improvements in clinical parameters in previously untreated patients and clinical stability in patients previously stabilized on enzyme replacement therapy.
Session topic: Platelet disorders 1
Keyword(s): Gaucher disease, Lysosomal storage disease, Outcome, Treatment
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