BlueRock Therapeutics Assessing the Potential of Cell Therapy for Parkinson Disease With Phase 1 Trial for Bemdaneprocel
In honor of World Brain Day, observed annually on July 22 by patient and clinician communities, CGTLive is taking a closer look at this ongoing study.
BlueRock Therapeutics’ bemdaneprocel (also known as MSK-DA01 and BRT-DA01), an investigational neuronal cell therapy, is currently being evaluated for the treatment of Parkinson disease (PD) in a phase 1 clinical trial (NCT04802733).1 In honor of World Brain Day, observed annually on July 22 by patient and clinician communities, CGTLive® is taking a closer look at this ongoing study.
The trial was initiated on May 3, 2021 and is being conducted by Claire Henchcliffe, MD, chair of the Department of Neurology, UCI School of Medicine, University of Califorina, Irvine, and colleagues. According to BlueRock’s website, the study remains active, but is no longer recruiting new patients, and according to the clinicaltrials.gov page the study’s actual enrollment was 12 patients.2
In the multicenter, open-label, nonrandomized, noncontrolled trial, all participants received a surgical transplantation of 1 of 2 different dose levels of bemdaneprocel cells to the postcommissural putamen bilaterally.2 The lower dose level comprised 0.9 million cells per putamen, and was administered to 5 patients in cohort A of the study. On the other hand, cohort B treated 7 patients at the higher dose level, which comprised 2.7 million cells per putamen.
The trial recruited patients at locations that included Weill Cornell Medicine in New York; University of California, Irvine; and University Health Network (UNH) in Toronto, Canada.3 Viviane Tabar, MD, chair of the Department of Neurosurgery at Memorial Sloan Kettering (MSK) Cancer Center and Andres Lozano, MD, PhD, FRCSC, FRSC, FCAHS, neurosurgeon and senior scientist, Krembil Brain Institute, University Health Network, Alan & Susan Hudson cornerstone chair in neurosurgery, Toronto Western Hospital, University Health Network and chairman of the Division of Neurosurgery at the University of Toronto(UoT) carried out the transplant surgeries for the trial.1 Henchcliffe is responsible for following patients at University of California, Irvine, Harini Sarva, MD, is following patients at Weill Cornell Medicine, and Alfonso Fasano, MD, PhD, the chair in neuromodulation and multi-disciplinary care at UHN and UoT, is following patients at the UNH site.
“Bemdaneprocel is a pluripotent stem cell therapy that's under investigational use for PD...” Daniel Kremens, MD, JD, an associate professor of neurology and codirector of the Parkinson’s Disease and Movement Disorders Center at Thomas Jefferson University, told CGTLive’s sister site NeurologyLive® at the 2024 American Academy of Neurology (AAN) Annual Meeting, held April 13-18, in Denver, Colorado. “I think this is really exciting time in PD, where we're looking at these truly not just symptomatic therapies, but disease-modifying therapies by introducing these pluripotent stem cells that are dopaminergic precursors to see whether we could really impact the actual disease state long-term.”
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The primary end point for the trial is safety and tolerability as assessed by the incidence of serious adverse events (SAEs) or abnormal tissue overgrowth related to the presence of the transplanted cells within the 1 year posttreatment timeframe. The trial’s secondary end points include the change in 18F-DOPA uptake using positron emission tomography (PET) as measured from baseline to 1 and 2 years; changes in the MDS-Unified Parkinson's Disease Rating Scale (UPDRS) motor sub-score in the "OFF" state and in the number of waking hours in the “OFF” state as measured from baseline to 2 years posttransplant; the incidence of SAEs at 2 years posttransplant; and the incidence and type of AEs at 1 year and 2 years posttransplant.
The study was open to patients aged 60 to 78 years old in the United States and patients aged 50 to 78 years old in Canada. Patients were required to have been diagnosed with PD from 3 to 20 years prior. Furthermore, patients were required to be taking levopoda, but with complications from the therapy, such as wearing off and/or dyskinesia. Participants were additionally required to be able to participate in all visits and assessments for the trial and to have a study partner who could act as a potential surrogate for long-term ongoing consent.
Patients who had a primary mitochondrial disorder, epilepsy, stroke, multiple sclerosis, or other neurodegenerative diseases were excluded from participation in the trial. Additional criteria for exclusion were prior treatment with deep brain stimulation, lesion therapy, or gene therapy for PD; prior surgery or radiation therapy on the brain or spinal cord; the inability to temporarily cease use of antiplatelet agents or other anticoagulant medications; any medical condition that would cause a high risk for use of immunosuppressants; any history of active malignancy within the past 5 years excepting treated basal cell carcinoma or in situ uterine cervical carcinoma; inability to undergo surgery or general anesthesia; a weight of over 350 lbs; or any other condition deemed by the investigator to make a patient unsuitable for participation. Patients who were pregnant or breastfeeding were also excluded.
In March 2024, BlueRock reported 18-month posttreatment data from the 12 patients who received bemdaneprocel in the study.1 The company noted that at this time point, the cell therapy remained well-tolerated and no major safety issues had occurred in the treated patients. Furthermore, at 18 months posttreatment, the patients treated at the high dose experienced a mean increase from baseline of 2.7 hours in the “ON” state and a 2.7 hour decrease for time in the “OFF” state. For patients treated at the low dose, a mean increase of 0.2 hours in the “ON” state compared to baseline was observed at 18 months posttreatment, with a corresponding mean decrease of 0.8 hours spent in the “OFF” state.
“It’s exciting that bemdaneprocel met safety and tolerability criteria at 12 months, and now the 18-month results suggest that these allogeneic cells survive and have potentially positive effects even after discontinuation of immunosuppressants,” Henchcliffe said in a March 2024 statement.1 “We should not overinterpret results of a phase 1 study, but this is a promising step that deserves to be followed up with further studies.”
BlueRock announced at the time that it planned to initiate a phase 2 clinical trial for bemdaneprocel at some point this year. More recently, in May 2024, bemdaneprocel was granted regenerative medicine advanced therapy (RMAT) designation by the FDA.4
“We are excited about the positive data from the bemdaneprocel phase 1 clinical trial and believe it has great potential to help patients living with PD regain functions they have lost to the disease,” Seth Ettenberg, the president and CEO of BlueRock Therapeutics said in a statement at the time.4 “Now with this RMAT designation in hand, we look forward to closely collaborating with the FDA to ready this program for phase 2 clinical studies.”
