Parkinson’s therapy Bemdaneprocel shows benefits up to 2 years
Patients had more time with controlled symptoms, per final trial data
Patients treated with bemdaneprocel, a cell therapy that Bluerock Therapeutics is developing for Parkinson’s disease, continue to spend more time with well-controlled symptoms and less time in off periods, when symptoms aren’t adequately controlled despite medication use.
That’s according to final data from exPDite (NCT04802733), a completed Phase 1 trial that involved 12 adults with Parkinson’s where bemdaneprocel — given as a high or low dose — was also found to be safe and well tolerated for up to 24 months.
“We are very excited to share the 24-month data from the exPDite trial which shows that bemdaneprocel could be a potentially meaningful treatment option for individuals living with Parkinson’s disease,” Amit Rakhit, chief development and medical officer at Bluerock, a subsidiary of Bayer, said in a company press release.
Rakhit said the study’s completion “sets the stage for the next phase of clinical development.” Patients who have completed the exPDite trial can roll over into a five-year extension (NCT05897957) study to be monitored for safety and clinical outcomes, and the company also plans to advance testing of bemdaneprocel into a placebo-controlled Phase 2 trial, expected to begin enrolling later this year.
The safety and efficacy data were scheduled to be presented at the International Congress of Parkinson’s Disease and Movement Disorders, held Sept. 27-Oct.1 in Philadelphia, and “support the continued development and evaluation of bemdaneprocel for the treatment of people with [Parkinson’s disease],” researchers wrote in an abstract.
Dopamine and Parkinson’s therapy
Parkinson’s symptoms occur when the brain’s dopaminergic neurons, or dopamine-producing nerve cells, are damaged and die over time. Dopamine is a chemical that helps control movement, so its gradual loss causes motor symptoms such as tremors and stiffness.
Levodopa is a mainstay treatment for Parkinson’s, and is converted into dopamine in the brain. While initially effective, continuous use of levodopa can lead to its effectiveness diminishing before the next scheduled dose, resulting in off periods marked by a resurgence or worsening of symptoms. These motor fluctuations become more frequent as the disease progresses.
Bemdaneprocel, previously known as BRT-DA01, involves transplanting dopamine-producing nerve cells into the brain through a surgical procedure. The therapy uses dopamine-making cells generated from human embryonic stem cells. The goal is for the transplanted cells to give rise to new neurons, easing symptoms.
“There is considerable momentum in the concept of restoring dopamine inputs in the brain using transplanted cells, and the positive results from the exPDite trial leads the drive forward,” said Claire Henchcliffe, MD, professor and chair of neurology at the University of California, Irvine, and one of the trial’s principal investigators.
The exPDite trial tested the safety and tolerability of bemdaneprocel in 12 adult patients who were experiencing off episodes despite being on levodopa. Their median age was 67 years, with a median time of nine years since Parkinson’s diagnosis.
Participants were randomly assigned to receive either a low dose (0.9 million cells) or a high dose (2.7 million cells) of bemdaneprocel into the putamen, a region of the brain that is involved in movement control, followed by a one-year course of immunosuppression to prevent the immune system from attacking the transplanted cells.
Consistent with earlier data, bemdaneprocel continued to be safe two years after the surgical procedure, with no side effects related to the cell therapy. Even after stopping immunosuppression, the transplanted cells continued to survive and form connections in the brain.
Patients who received the higher dose saw a reduction of 21.9 points in part III of the MDS-Unified Parkinson’s Disease Rating Scale, which measures motor symptoms, while those in the low-dose group saw a reduction of 8.3 points. Lower scores on the scale indicate less severe symptoms. These reductions were observed while patients were off medication.
On time, off time
The study also tracked the time patients spent with well-controlled symptoms and off episodes. Those in the high-dose group had a mean increase of 1.8 hours in good on state when compared to the beginning of the study. Good on state refers to periods of time when a patient experiences satisfactory control of their motor symptoms due to the optimal effect of levodopa.
Patients in the high-dose group also experienced a reduction in the time spent in the off state, with an average decrease of 1.9 hours from the beginning of the study.
Those in the low dose group had a mean decrease of 0.8 hours in good on time and a mean increase of 0.4 hours in off time, compared with the beginning of the study.
Participants who received the high dose of bemdaneprocel were better able to perform daily tasks, based on the MDS-UPDRS part II scale, with an average decrease of 3.4 points compared with the initial measurements. Those in the low dose cohort experienced a decline, as indicated by a mean increase of 2.0 points on this scale.
“The transplanted cells survive and there are early signs that bemdaneprocel can potentially help patients to better control their motor symptoms,” Henchcliffe said. “These are exciting results that warrant further exploration in a next phase placebo-controlled study.”
Christian Rommel, head of research and development at Bayer’s pharmaceuticals division, called the results “encouraging, saying they ““support our commitment in developing innovative therapies that can significantly improve patient lives.”
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