Eliglustat substrate reduction therapy in children with Gaucher disease type 1

Noor Ul Ain ¹ Armaan Saith ^1* Audrey Ruan ^1* Ruhua Yang ¹ Aaron Burton ^2* Pramod K Mistry ^1*

• ¹ Department of Internal Medicine, School of Medicine, Yale University, New Haven, Connecticut, United States
• ² Yale New Haven Health System, New Haven, Connecticut, United States

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.