Objective:

Background:

Bemdaneprocel, an investigational therapy under development for PD, comprises midbrain dopaminergic neuron progenitors derived from embryonic stem cells. exPDite (NCT04802733), a Phase 1, open-label, 24-month, multicenter study demonstrated bemdaneprocel was generally safe and well tolerated with potential clinical benefit through 24 months post transplantation. The exPDite-2 trial will evaluate the efficacy and safety of bemdaneprocel.

Design/Methods:

Eligible participants with clinically established PD, ≥45 to ≤75 years of age, ≥4 and <12 years from PD diagnosis with ≥2.5 hours daily OFF time will be randomized to bemdaneprocel or sham surgery in a single surgical session. Bemdaneprocel is administered bilaterally to the postcommissural putamen (3 million cells/putamen); sham surgery consists of bilateral partial burr holes. The procedure will be followed by 12 months of active (bemdaneprocel group) or placebo (sham group) immunosuppression. Sham group participants may be eligible to receive bemdaneprocel during the open-label period based on the primary analysis at Week 78.

Results:

The primary endpoint is change from baseline at Week 78 in adjusted PD diary ON time without troublesome dyskinesia. Secondary and exploratory endpoints include motor, non-motor, activities of daily living, quality of life, and safety outcomes. All participants receiving bemdaneprocel will be followed for 5 years post transplantation. Approximately 102 participants will be randomized in exPDite-2. The first participant was randomized and underwent surgery in August 2025.

Conclusions:

exPDite-2 is a Phase 3, randomized, sham surgery–controlled, double-blind trial that will evaluate the efficacy and safety of bemdaneprocel. exPDite-2 will be the first large-scale, potentially registrational trial of stem cell–derived midbrain dopaminergic neuron progenitors in people with PD.