Dopaminergic Neuronal Cell Therapy for Parkinson’s Disease: Results From a Phase 1 Study of Bemdaneprocel

Objective

Current treatments for Parkinson’s disease (PD) do not address dopaminergic neuron loss, an underlying cause of disease. In addition, current treatments do not impact disease progression and lose effectiveness over time.^1,2

Bemdaneprocel (BRT-DA01) is an investigational therapy comprised of dopaminergic neurons derived from pluripotent stem cells.³ Studies in Parkinsonian mouse models showed no significant safety findings in biodistribution, toxicology or tumorigenicity studies. Preclinical efficacy was demonstrated in rats.²

We report the Year 1 outcomes of a multi-center, multi-site, open-label, non-randomized, Phase 1 (NCT04802733) study to assess the safety and tolerability, as well as exploratory efficacy measures, of bemdaneprocel in participants with PD.

Methods

• Participants were sequentially recruited into this Phase 1 study.
• The first five participants were enrolled into the low-dose group (0.9 million cells per putamen) and subsequent participants were enrolled into the high-dose group (2.7 million cells per putamen) (Figure 1).
• Cells were administered in a single session of stereotactically guided surgical injection into the posterior putamen bilaterally through a single burr hole on each side.
• An immunosuppressive regimen was initiated intraoperatively and continued post-operatively for 1 year.
• The primary objective of the study was to assess safety and tolerability, with a primary endpoint measuring the incidence of serious adverse events (SAEs) at 1-year post-transplant.

Results

• There were no reports of an AE or SAE related to bemdaneprocel (Table 2).
• There was 1 SAE of seizure that was transient and attributed to the surgical procedure, reported in Cohort B.
• There were no discontinuations or deaths in the study.
• There were no graft-induced dyskinesias seen in either cohort.
• At a group level there was an increase in 18F-DOPA uptake in the posterior putamen (transplant site), which did not associate with the degree of baseline 18F-DOPA uptake (Figure 3).
• Analysis of clinical scores may suggest improvement in MDS-UPDRS Part III (OFF state), a decrease in OFF time, and an increase in Good ON time without troublesome dyskinesia.

Conclusions

• Bemdaneprocel was generally safe and well tolerated in these 12 participants at 1-year post-transplantation.
• The stereotactic surgical delivery and therapeutic regimen was feasible, with all participants receiving the planned dose of bemdaneprocel and tolerating the 1-year immunosuppression regimen.
• Evidence of bemdaneprocel survival and engraftment was demonstrated in the posterior putamen by 18F-DOPA PET imaging.