Blood Journal
Leading the way in experimental and clinical research in hematology

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

  1. Elena Lukina1,
  2. Nora Watman2,
  3. Elsa Avila Arreguin3,
  4. Maryam Banikazemi4,
  5. Marta Dragosky5,
  6. Marcelo Iastrebner5,
  7. Hanna Rosenbaum6,
  8. Mici Phillips7,
  9. Gregory M. Pastores8,
  10. Daniel I. Rosenthal9,
  11. Mathilde Kaper10,
  12. Tejdip Singh10,
  13. Ana Cristina Puga10,
  14. Peter L. Bonate11, and
  15. M. Judith Peterschmitt10,*
  1. 1 Hematology Research Center, Russian Academy of Medical Sciences, Moscow, Russian Federation;
  2. 2 Hospital Ramos Mejia, Buenos Aires, Argentina;
  3. 3 Instituto Mexicano del Seguro Social, Hospital de Especialidades, Mexico City, Mexico;
  4. 4 Columbia University, New York, NY, United States;
  5. 5 Instituto Argentino de Diagnostico y Tratamiento, Buenos Aires, Argentina;
  6. 6 Rambam Medical Center, Haifa, Israel;
  7. 7 Shaare Zedek Medical Center, Jerusalem, Israel;
  8. 8 New York University, New York, NY, United States;
  9. 9 Massachusetts General Hospital, Boston, MA, United States;
  10. 10 Genzyme Corporation, Cambridge, MA, United States;
  11. 11 GlaxoSmithKline, Research Triangle Park, NC, United States
  1. * Corresponding author; email: judith.peterschmitt{at}


Eliglustat tartrate (Genz-112638), a specific inhibitor of glucosylceramide synthase, is under development as an oral substrate reduction therapy for Gaucher disease type 1 (GD1). A multinational, open-label, single-arm Phase 2 study of 26 GD1 patients (16F:10M; mean age 34 years) evaluated the efficacy, safety, and pharmacokinetics of eliglustat tartrate administered twice daily by mouth at 50- or 100-mg doses based on plasma drug concentrations. Entry criteria required splenomegaly with thrombocytopenia and/or anemia. The composite primary efficacy endpoint required improvement after 52 weeks in ≥2 of these 3 disease manifestations and was met by 77% (95%CI=58,89) of all patients and 91% (95%CI=72,98) of the 22 patients completing 52 weeks. Statistically significant improvements occurred in mean hemoglobin level (+1.62 g/dL; 95%CI=+1.05,+2.18), platelet count (+40.3%; 95%CI=+23.7,+57.0), spleen volume (-38.5 %; 95%CI=-43.5,-33.5), liver volume (-17.0%; 95%CI=-21.6,-12.3), and lumbar spine bone mineral density (+0.31 Z-score; 95%CI =+0.09,+0.53). Elevated biomarkers (chitotriosidase; chemokine CCL18; angiotensin converting enzyme; tartrate-resistant acid phosphatase) decreased by 35-50%. Plasma glucosylceramide and ganglioside GM3 normalized. Eliglustat tartrate was well tolerated: 7 mild, transient adverse events in 6 patients were considered treatment-related. Individual pharmacokinetics varied; mean Tmax=2.3 and mean t1/2=6.8 hours. Eliglustat tartrate appears to be a promising oral treatment for GD1. This study is registered at as NCT00358150.

  • Submitted March 11, 2010.
  • Accepted March 31, 2010.