Eliglustat substrate reduction therapy in children with Gaucher disease type 1.

Abstract

Importance: Gaucher disease (GD) is a rare lysosomal storage disorder with limited treatment options for pediatric patients. Oral substrate reduction therapy (SRT) with eliglustat offers a potential alternative, particularly for those with barriers to enzyme replacement therapy (ERT).

Objective: Evaluate the safety and efficacy of eliglustat SRT in pediatric patients with type 1 Gaucher disease (GD1), both as initial therapy and as a switch from intravenous ERT.

Design: A prospective case series was conducted from 2017 to 2024.

Setting: Yale's National Gaucher Disease Treatment Center, New Haven, CT, United States.

Participants: Fourteen pediatric GD1 patients with significant barriers to receiving ERT.

Intervention: Eliglustat SRT was dosed pharmacogenomically based on CYP2D6 metabolizer status.

Primary outcomes and measures: Primary outcomes included safety and efficacy in reversing indicators of disease activity. Secondary outcomes involved changes in patient and parent-reported quality of life, assessed using PROMIS questionnaires.

Results: Eliglustat was initiated at a mean age of 12.5 years (range: 6-17 years) and administered for a mean duration of 3.6 years (range: 1-7 years). All patients remained on treatment and exhibited sustained reductions in glucosylsphingosine (GlcSph) levels compared to baseline (p = 0.005). Other disease indicators demonstrated corresponding improvements. Adverse effects were limited to transient gastroesophageal reflux in 3/14 patients (21%). Serial electrocardiograms (EKGs) were normal. Growth and developmental milestones were appropriate for age in all patients. Patients and their parents reported a global improvement in quality of life.

Conclusions: Eliglustat demonstrated significant clinical benefits in pediatric GD1 patients, as evidenced by reductions in GlcSph levels and other disease indicators. The therapy showed a favorable safety profile comparable to that observed in adults. These findings suggest eliglustat is a promising therapeutic option for pediatric GD1 patients, providing an effective alternative to ERT.