After a year of treatment, patients showed significant improvements in ON time without troublesome dyskinesia, with more apparent effects observed in the high-dose group.
New data from a first-in-human phase 1 study (NCT04802733) assessing bemdaneprocel (BlueRock Therapeutics/Bayer), an investigational cell therapy, showed that the agent met its primary objective of safety, with encouraging results on other measures of motor and nonmotor outcomes. Based on these results, the companies are planning for a phase 2 trial that is expected to begin enrolling patients in the first half of 2024.1,2
Presented at the 2023 International Congress of Parkinson’s Disease and Movement Disorders (MDS), held August 27-31, in Copenhagen, Denmark, the open-label, non-controlled study included 12 individuals with PD (average age, 66.4 [57-77] years) with a mean time of 9.1 years since diagnosis. At the time of the analysis, patients had received at least 1 of 2 different doses of the cell therapy to the post-commissural putamen bilaterally, along with a 1-year immunosuppressive regimen.
In the 5 individuals assigned to the low-dose cohort who completed 1-year follow-up, 31 AEs were reported, all of which were considered mild to moderate in severity except for 1 case of fall. No serious AEs were attributed to bemdaneprocel after 1 year; however, investigators did note 2 unrelated serious AEs of seizure attributed to the surgical procedure and 1 COVID case. Both of these resolved without sequelae. Above, all, there were no AEs reported as possibly related to the cell therapy.
"The data from this Phase I open label study are extremely encouraging,” principal investigator Claire Henchcliffe, MD, chair of the Department of Neurology, UCI School of Medicine, University of Califorina, Irvine, said in a statement.1 "While this is a small open label study, meeting the study’s primary objective for safety and tolerability along with initial improvements seen in clinical outcomes represents a great step forward. The hope now is that these trends continue and translate into meaningful benefit for people with Parkinson’s disease in controlled clinical trials."
In the study, patients received surgical transplantation of 1 of 2 different dose levels: cohort A received a dose of 0.9 million cells per putamen, while cohort B received 2.7 million cells per putamen. Bemdaneprocel, also known as BRT-DA01, is pluripotent stem cell-based approach designed to replace the dopamine producing neurons lost from PD. When transplanted, these neuron precursors have the potential to reform neural networks that have been severely affected by PD and restore motor and nonmotor function to patients.
In the high-dose cohort, treated patients showed a reduction of 13.0 points in MDS-Unified Parkinson’s Disease Rating Scale-III scores at 1 year in comparison with baseline. Less pronounced, the low-dose cohort showed a reduction of 7.6 points. Imaging analysis using 18F-DOPA PET, a technique used to visualize and assess dopaminergic activity, showed evidence of cell survival and engraftment in both the high and low dose cohorts. All assessments, including safety and tolerability, evidence of cell survival and motor effects, and feasibility of transplantation, will continued to be assessed over the final year of the 2-year study.
"The standard of care for millions of people living with Parkinson’s disease has only marginally improved in the past decades, and the existing unmet medical need will only become higher due to the growing aging population," Christian Rommel, member of the executive committee, Bayer’s Pharmaceuticals Division, and head of Research and Development, said in a statement. "The positive outcome of this Phase I clinical trial is a clear step forward, and it brings us closer to delivering new treatment options to patients."
Using the Hauser Diary, participants in the high-dose cohort showed an improvement of 2.16 hours in ON time without troublesome dyskinesia compared with baseline after 1 year while also decreasing 1.91 hours of OFF time throughout the same period. The low-dose cohort demonstrated an improvement of 0.72 hours of ON time and a decrease of 0.75 hours in OFF state time during that period as well.