Outcomes after 8 years of eliglustat therapy for Gaucher disease type 1: Final results from the Phase 2 trial

Am J Hematol. 2019 Jan;94(1):29-38. doi: 10.1002/ajh.25300. Epub 2018 Oct 26.

PMID: 30264864

Elena Lukina, Nora Watman, Marta Dragosky, Heather Lau, Elsa Avila Arreguin, Hanna Rosenbaum, Ari Zimran, Meredith C Foster, Sebastiaan J M Gaemers, M Judith Peterschmitt

Summary: Eliglustat is first-line oral therapy for adults with Gaucher disease type 1 (GD1). GD1 patients using this therapy for eight years were studied and their patients observed clinically significant improvements in all measures, with the most significant improvements being noted in the most severely affected patients.

Abstract

Objective: Eliglustat is a first-line oral treatment for adults with Gaucher disease type 1 (GD1) with CYP2D6-metabolizer phenotypes of poor, intermediate, or extensive (>90% of patients). This study presents the final results of a Phase 2 trial and extension (NCT00358150) in previously untreated adult GD1 patients with splenomegaly, thrombocytopenia, and/or anemia who received 50 or 100 mg eliglustat tartrate (equivalent to 42 or 84 mg eliglustat) twice daily for 8 years.

Results: The trial was completed by 19 of the 26 patients. Mean spleen and liver volumes decreased by 69% and 34%, respectively, after 8 years of eliglustat treatment. The mean hemoglobin concentration and platelet count increased by 2.2 g/dL and 113%, respectively. All of the patients met at least three of the four treatment goals set for long-term enzyme replacement therapy patients. Individuals with severe splenomegaly (n = 6), moderate-to-severe anemia (n = 6), or severe thrombocytopenia (n = 8) had mean final values that were similar to patients with milder illness at baseline and within long-term therapeutic goal thresholds. Biomarker median percent changes from baseline for chitotriosidase, CCL18, glucosylsphingosine, and plasma glucosylceramide were -91%, -87%, -92%, and -80%, respectively. The mean T-score of the lumbar spine increased by 0.96, bringing it out of the osteopenic range to the normal range. The mean quality-of-life scores, which were largely below normal at the start, gradually improved to levels seen in healthy individuals.

Conclusion: Eliglustat was well tolerated, with 98% of side effects being mild or moderate and 94% being unrelated to treatment. Over the course of eight years, clinically meaningful improvements in all measures remained or were sustained, with the most significant improvements noted in the most severely affected patients.

Keywords: Gaucher disease; Eliglustat; Eliglustat tartrate; Phase 2 trial; splenomegaly; anemia; thrombocytopenia; biomarker; treatment