Bemdaneprocel Moves to Phase 2 Study in Parkinson Disease After Positive Phase 1 Data
Significant improvements in ON time without troublesome dyskinesia were reported with the cell therapy after 1 year, with more apparent effects observed in the high-dose group.
A version of this article originally appeared on our sister site, NeurologyLive.
Claire Henchcliffe, MD, DPhil
Bemdaneprocel, an investigational cell therapy from BlueRock Therapeutics and Bayer previously known as BRT-DA01, has met its primary safety target in a first-in-human phase 1 study (NCT04802733), with additional encouraging results on other measures of motor and nonmotor outcomes among participants with Parkinson disease (PD).1
The data were presented at the 2023 International Congress of Parkinson’s Disease and Movement Disorders (MDS), held August 27-31, in Copenhagen, Denmark, by Claire Henchcliffe, MD, DPhil, the Chair and Stanley van den Noort Professor of Neurology at the University of California, Irvine. Based on the data, the companies announced that a planned phase 2 trial is expected to begin enrolling patients in the first half of 2024.1,2
In the open-label, noncontrolled study, 12 individuals with PD (average age, 66.4 years) with a mean time of 9.1 years since diagnosis were treated with at least 1 of 2 doses of bemdaneprocel to the postcommissural putamen bilaterally. This was in line with a 1-year immunosuppressive regimen.
The low-dose cohort (Cohort A) included 5 patients who completed 1-year follow-up, among whom 31 total AEs were reported. All were considered mild to moderate in severity save for 1 case of fall, but no serious AEs were attributed to bemdaneprocel after 1 year. Notably, Investigators did acknowledge 2 unrelated serious AEs of seizure attributed to the surgical procedure and 1 COVID-19 case, though both resolved without sequelae. Above, all, there were no AEs reported as possibly related to the cell therapy.
"The data from this phase 1 open-label study are extremely encouraging,” Henchcliffe, the study's principal investigator, said in a statement.2 "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."
The surgical transplantation included dose levels of 0.9 million cells per putamen (Cohort A) and 2.7 million cells per putamen (Cohort B; n = 7). Bemdaneprocel is a 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.
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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.
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.
"The standard of care for millions of people living with Parkinson 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 in Bayer’s Pharmaceuticals Division and head of Research and Development, said in a statement.2 "The positive outcome of this phase 1 clinical trial is a clear step forward, and it brings us closer to delivering new treatment options to patients."
