Clinical outcomes after 4.5 years of eliglustat therapy for Gaucher disease type 1: Phase 3 ENGAGE trial final results

Am J Hematol. 2021 Jun 23. doi: 10.1002/ajh.26276. Online ahead of print.

PMID: 34161616

Pramod K Mistry, Elena Lukina, Hadhami Ben Turkia, Suma P Shankar, Hagit Baris Feldman, Marwan Ghosn, Atul Mehta, Seymour Packman, Heather Lau, Milan Petakov, Sarit Assouline, Manisha Balwani, Sumita Danda, Evgueniy Hadjiev, Andres Ortega, Meredith C Foster, Sebastiaan J M Gaemers, M Judith Peterschmitt

Highlights: During 4.5 years of treatment, Eliglustat was well tolerated and resulted to clinically substantial improvements in previously untreated individuals with Gaucher disease type 1.

Abstract

Objective: Eliglustat is an oral substrate reduction medication that has been approved for adults with Gaucher disease type 1 who meet certain criteria. In the 9-month primary analysis of the Phase 3 ENGAGE trial, eliglustat-treated patients demonstrated statistically significant improvements in organ sizes and hematologic markers compared to placebo in previously untreated people with Gaucher disease type 1. This study reports final outcomes by time on eliglustat among all patients who participated in the ENGAGE trial and extension.

Results: No patient had a clinical deterioration or withdrew due to adverse events; 39/40 patients entered the open-label extension period, and 34/40 (85%) stayed in the trial until it was completed or switched to commercial eliglustat after its approval (2.3–6 years). All patients had clinically meaningful improvements in Gaucher disease symptoms, which were concomitant with lower levels of pathological lipid substrate (glucosylceramide and glucosylsphingosine). Among patients with 4.5 years of eliglustat exposure, mean spleen volume decreased by 66% (from 17.1 to 5.8 multiples of normal [MN], n = 13), mean liver volume decreased by 23% (from 1.5 to 1.1 MN, n = 13), mean hemoglobin increased 1.4 g/dl (from 11.9 to 13.4g/dl, n = 12), mean platelet count increased by 87% (from 67.6 to 122.6 _ 109/L, n = 12), median chitotriosidase decreased by 82% (from 13 394 to 2312 nmol/h/ml, n = 11), median glucosylceramide decreased by 79% (from 11.5 to 2.4 μg/ml, n = 11), median glucosylsphingosine decreased by 84% (from 518.5 to 72.1 ng/ml, n = 10), and mean spine T-score increased from -1.07 (osteopenia) to -0.53 (normal) (n = 9).

Conclusion: The full trial cohort experienced similar improvements in Gaucher disease symptoms and biomarkers over time. During 4.5 years of treatment, Eliglustat was well tolerated and resulted to clinically substantial improvements in previously untreated individuals with Gaucher disease type 1.

Keywords: Gaucher disease type 1; Eliglustat