Cell Therapy Bemdaneprocel Advances to Phases 3 Registrational Trial in Parkinson Disease

Amit Rakhit, MD, MBA

Bayer AG and BlueRock Therapeutics have unveiled new details into a phase 3 registrational trial dubbed exPDite-2 that will assess the efficacy and safety of bemdaneprocel, an investigational cell therapy that replaces lost dopaminergic producing neurons, in patients with Parkinson disease (PD). The study, a first-of-its-kind in the field, is anticipated to begin in the first half of 2025 and depending on the outcome, are intended to be a part of a robust data package for future regulatory submissions.¹

The study, the first such phase 3 trial testing an allogeneic pluripotent stem cell therapy in PD, is expected to be a randomized, sham surgery-controlled double-blind trial featuring approximately 102 patients with moderate levels of the disease. In an attempt to build on positive phase 1 data, the study will use change in PD diary measure of ON time without troublesome dyskinesia, adjusted for a 16-hour walking day, over a 78-week period as the primary end point.

Bemdaneprocel, otherwise known as BRT-DA01, is a stem cell approach in which neuron precursors are implanted into the brain of a person with PD through a surgical procedure. When transplanted, these neuron precursors have the potential to re-form neural networks that have been severely impacted by the disease and to potentially restore motor and non-motor function to patients. To date, the investigational product has received fast track and regenerative medicine advance therapy designations from the FDA.

"We are thrilled to take this critical step in our development program towards further investigating a potential new therapeutic option for people living with Parkinson disease,” Amit Rakhit, MD, MBA, chief development and medical officer at BlueRock, said in a statement.¹ "exPDite-2 is the first registrational Phase III clinical trial for an investigational pluripotent stem cell derived therapy in Parkinson disease and we look forward to working closely with clinical investigators and the Parkinson disease community as we initiate this trial."

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Bemdaneprocel first showed promising outlook in the phase 1 exPDite trial, a multicenter, open-label, non-randomized, non-controlled study of 12 patients with PD. In the study, patients received surgical transplantation of 1 or 2 different doses (cohort 1: 0.9 million cells per putamen; n = 5; cohort 2: 2.7 million cells per putamen; n = 7) of the cell therapy to the post-commissural putamen bilaterally, along with administration of a 1-year immunosuppression regimen. Positive 24-month data from exPDite was first announced in late September 2024 and shortly after at the 2024 International Congress of Parkinson’s Disease and Movement Disorders (MDS).²

At 24 months, the safety profile of bemdaneprocel was consistent with earlier findings, as investigators observed no adverse events (AEs) related to the treatment. In the high dose cohort, patients demonstrated a mean reduction of 21.9 points in Unified Parkinson’s Disease Rating Scale (UPDRS) Part III compared with baseline while the low dose cohort demonstrated mean decreases of 8.3 points. Furthermore, at this time point, there was a mean reduction of 3.4 points and 2.0 points in the high and low-dose cohorts, respectively, on MDS-UPDRS Part II, a measure of activities of daily living.

Using the Hauser PD Diary, those in the high dose cohort demonstrated a mean increase of 1.8 hours in time spent in the good ON state without troublesome dyskinesias and a mean decrease of 1.9 hours in time spent in the OFF state at month 24 relative to baseline. The low dose cohort experienced less significant effects, with a mean decrease of 0.8 hours in good ON time and a mean increase of 0.4 hours in OFF state time. Above all, transplanted cells continued to survive and engraft in the brain after discontinuing immunosuppression therapy at 12 months as outlined in the study’s protocol.

"With the planned initiation of the Phase III clinical trial, we are committed to bringing bemdaneprocel faster to patients in need,” Christian Rommel, member of the executive committee of Bayer’s Pharmaceuticals Division, and Global Head of Research and Development, said in a statement.¹ "It represents a significant milestone in our efforts to advance our cell and gene therapy pipeline and deliver on our ambition to be an industry leader in this space."

At MDS 2024, Rakhit sat down with NeurologyLive to discuss the 24-month findings and the innovation behind stem cell therapy for PD. In the clip below, he spoke on the design of the trial, the challenges in testing a new mechanism of action, and the importance of identifying the right patients who may be eligible for cell therapy treatment.

REFERENCES
1. BlueRock Therapeutics advances investigational cell therapy bemdaneprocel for treating Parkinson’s disease to registrational Phase III clinical trial. News release. BlueRock Therapeutics. January 13, 2025. Accessed January 13, 2025. https://www.bluerocktx.com/bluerock-therapeutics-advances-investigational-cell-therapy-bemdaneprocel-for-treating-parkinsons-disease-to-registrational-phase-iii-clinical-trial/
2. BlueRock Therapeutics’ investigational cell therapy bemdaneprocel for Parkinson’s disease shows positive data at 24-months. News release. BlueRock Therapeutics. September 27, 2024. Accessed January 13, 2025. https://www.bayer.com/media/en-us/bluerock-therapeutics-investigational-cell-therapy-bemdaneprocel-for-parkinsons-disease-shows-positive-data-at-24-months/