BlueRock Therapeutics' Parkinson Disease Cell Therapy Bemdaneprocel Shows Initial Efficacy in Phase 1 Trial

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In light of the promising results, BlueRock is preparing for a phase 2 trial.

BlueRock Therapeutics’ bemdaneprocel (BRT-DA01), an investigational neuronal cell therapy intended to treat Parkinson disease (PD), has demonstrated initial improvements in several exploratory efficacy end points in addition to meeting the primary safety end point in a phase 1 clinical trial (NCT04802733) in patients with PD.1 In light of the promising results, the company is preparing for a phase 2 trial with initiation of enrollment for that study anticipated in the first half of next year.

Bemdaneprocel, which was administered via bilateral surgical transplantation to the to the post-commissural putamen, consists of dopaminergic neuron precursors derived from pluripotent embryonic stem cells. The study treated 12 patients in total across the lower dose (0.9 million cells per putamen) cohort A (n = 5) and the higher dose (2.7 million cells per putamen) cohort B (n = 7). The trial is being carried out in collaboration with Memorial Sloan Kettering Cancer Center.

The study’s exploratory end points for efficacy included the change in waking hours in the Hauser Diary’s “OFF” state, defined by that tool as a state in which patients experience a worsening of their symptoms that stands in contrast to the “ON” state in which symptoms are well-controlled. BlueRock noted that, in comparison to baseline measurements, at the 1 year time point patients in cohort B experienced an increase in 2.16 hours in the “ON” state without troubling dyskinesia and a corresponding 1.91 hour decrease for time in the “OFF” state. For cohort A, a 0.72 hour increase in time in the “ON” state without troubling dyskinesia and a 0.75 hour decrease in time in the “OFF” state, likewise compared to baseline, was reported.

Another exploratory end point for efficacy measured the change from baseline in the MDS-Unified Parkinson's Disease Rating Scale (UPDRS) Part III motor sub-score in the “OFF” state at the 1 year time point. BlueRock reported that in cohort B an improvement of 13.0 points was observed and that in cohort A an improvement of 7.6 points was observed.

“The standard of care for millions of people living with PD 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, PhD, a member of the Executive Committee of Bayer’s Pharmaceuticals Division and head of Research and Development, said in a statement.1 “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”.

In terms of safety, with no serious adverse events (SAEs) related to the cell therapy having occurred at 1 year posttransplant, the trial met its primary end point for safety and tolerability; although, 1 patient experienced a serious seizure deemed related to the surgical administration. An additional unrelated treatment-emergent SAE in the trial occurred in the form of a case of COVID-19. BlueRock stated that the SAEs resolved without sequelae. Furthermore, the company noted that in both cohort A and cohort B, 18F-DOPA PET imaging scans indicated cell survival and engraftment at 1 year posttransplant, thus meeting the first part of a secondary end point.

“The data from this phase 1 open-label study are extremely encouraging” Claire Henchcliffe, MD, the chair of the University of California, Irvine, School of Medicine Department of Neurology and a principal investigator for the trial, added to the 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 PD in controlled clinical trials.”

Bemdaneprocel is among several cell therapies and gene therapies currently in development for the treatment of PD. Earlier this month, Aspen Neuroscience received clearance from the FDA for an investigational new drug application for ANPD001, an investigational autologous induced pluripotent stem cell derived therapy intended to treat PD.2 In February of this year, NKGen Biotech’s SNK01, also in development for the treatment of solid tumors, was approved by the FDA for compassionate use in a patient with PD.3 Seelos Therapeutics’ SLS-004, an investigational gene therapy candidate for the treatment of PD, has generated promising data in preclinical research.4 Furthermore, Bloomsbury Genetic Therapies is developing adeno-associated virus vector-based gene therapy BGT-DTDS for the treatment dopamine transporter deficiency syndrome, a disease that causes parkinsonism-like features.5

REFERENCES
1. BlueRock’s phase I study with bemdaneprocel in patients with Parkinson’s disease meets primary endpoint. News release. Bayer AG and BlueRock Therapeutics LP. August 28, 2023. Accessed August 28, 2023. https://www.bluerocktx.com/bluerocks-phase-i-study-with-bemdaneprocel-in-patients-with-parkinsons-disease-meets-primary-endpoint/
2. Aspen Neuroscience announces FDA clearance of investigational new drug application for ANPD001, autologous cell therapy for the treatment of Parkinson’s disease. News release. Aspen Neuroscience. August 8, 2023. Accessed August 28, 2023. https://aspenneuroscience.com/aspen-neuroscience-announces-fda-clearance-of-investigational-new-drug-application-for-anpd001-autologous-cell-therapy-for-the-treatment-of-parkinsons-disease/
3. NKMAX's NK cell therapy for Parkinson’s scores FDA compassionate use approval. News release. NKMAX. February 23, 2023. Accessed August 28, 2023. https://www.koreabiomed.com/news/articleView.html?idxno=20514
4. Seelos Therapeutics announces data demonstrating downregulation of alpha synuclein in an in vivo gene therapy study of SLS-004 utilizing CRISPR-dCas9 in Parkinson's disease. News release. Seelos Therapeutics, Inc. December 15, 2022. Accessed August 28, 2023. https://seelos.irpass.com/profiles/investor/NewsPrint.asp?v=6&b=2376&ID=114509&m=rl&g=1201
5. Bloomsbury Genetic Therapies receives rare paediatric disease designation from the U.S. FDA for BGT-DTDS for the treatment of dopamine transporter deficiency syndrome (DTDS). News release. Bloomsbury Genetic Therapies Limited. May 3, 2023. Accessed August 28, 2023. https://bloomsburygtx.com/bloomsbury-receives-rare-paediatric-disease-designation-from-the-u-s-fda-for-bgt-dtds-for-the-treatment-of-dopamine-transporter-deficiency-syndrome-dtds/
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