Encore: A Randomized, Controlled, Open-Label Non-Inferiority Study Comparing Eliglustat To Imiglucerase In Gaucher Disease Type 1 Patients On Enzyme Replacement Therapy Who Have Reached Therapeutic Goals

Gaucher disease type 1 is a multi-systemic lysosomal storage disorder caused by acid β-glucosidase deficiency. Eliglustat is a novel oral substrate-reduction therapy in development for adults with Gaucher disease type 1. This Phase 3 trial (ENCORE, NCT00943111, sponsored by Genzyme, a Sanofi company) compares eliglustat with imiglucerase in patients who had reached pre-specified therapeutic goals on enzyme replacement therapy.

ENCORE is a randomized (2:1 eliglustat: imiglucerase), controlled, open-label non-inferiority trial of 159 patients previously receiving enzyme replacement therapy for ≥ 3 years who had met therapeutic goals. The primary efficacy endpoint was percent of patients remaining stable after 52 weeks of treatment (using a pre-specified composite of spleen, liver, hemoglobin, and platelet parameters).

As this was a non-inferiority trial, efficacy analyses were done on the per protocol population, which consisted of 99 eliglustat and 47 imiglucerase patients. Eliglustat was statistically non-inferior to imiglucerase: 84% of eliglustat and 94% of imiglucerase patients maintained goals for all 4 parameters (lower bound of 95% CI of difference [-18.6%] within the pre-specified [-25%] non-inferiority margin). Individually, 94% of eliglustat patients maintained stability criteria for spleen, 95% for hemoglobin, 96% for liver, and 93% for platelets. Of the 16/99 eliglustat patients who did not meet stability criteria based on change from baseline, most patients (13/16) maintained absolute values for the individual endpoints that remained within published therapeutic goals (Pastores Semin Hematol, 2004). Baseline bone mineral density scores were normal in most patients and remained normal on eliglustat. Two eliglustat patients and one imiglucerase patient (2% in each arm) discontinued because of an adverse event. Over the course of 52 weeks, 4 adverse events were observed with ≥ 10% incidence compared with imiglucerase: fatigue (14% vs. 2%) headache (13% vs. 2%), nausea (12% vs 0%), and upper abdominal pain (10% vs. 0%). The majority of adverse events were mild or moderate in severity for both groups. There were no treatment-related serious adverse events.

In the Phase 3 ENCORE study, eliglustat was well tolerated and was non-inferior to imiglucerase in maintaining stability for 52 weeks in previously treated patients with Gaucher disease type 1.

Burrow:Genzyme, a Sanofi company: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Biomarin: Consultancy, Honoraria. Balwani:Genzyme, a Sanofi company: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees. Cox:Genzyme, a Sanofi company: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees. Drelichman:Genzyme, a Sanofi company: Consultancy, Honoraria. Cravo:Genzyme, a Sanofi company: Consultancy, Honoraria. Martins:Genzyme, a Sanofi company: Consultancy, Honoraria, Speakers Bureau; Shire: Consultancy, Honoraria; Actelion: Consultancy, Honoraria; Biomarin: Consultancy, Honoraria. Lukina:Genzyme, a Sanofi company: Consultancy, Honoraria, Speakers Bureau. Rosenbloom:Genzyme, a Sanofi company: Consultancy, Honoraria. Ross:Genzyme, a Sanofi company: Employment. Angell:Genzyme, a Sanofi company: Employment. Puga:Genzyme, a Sanofi company: Employment.