BlueRock Advances Cell Therapy For Parkinson's Disease

By Erin Harris, Editor-In-Chief, Cell & Gene
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BlueRock Therapeutics has moved decisively into the Phase III pivotal phase with the exPDite-2 study evaluating bemdaneprocel for Parkinson’s disease. Drawing lessons from earlier research, Senior Vice President and Project Lead Gabi Belfort, M.D., Ph.D., emphasized two central findings from the open-label Phase I trial. “At two different dose levels, bemdaneprocel had a favorable safety profile with no adverse events related to the treatment over the 2-year duration of the study,” Dr. Belfort explained. “The higher dose also delivered ‘encouraging changes on clinical measures used to assess Parkinson’s disease,’ according to a result published in Nature following an 18-month data cut.”

The decision to progress with the high dose in exPDite-2 is a direct response to these promising results. “Given the data from the Phase I study, the high dose was selected for testing in the exPDite-2 randomized control trial,” said Dr. Belfort. Unlike Phase I, exPDite-2 is a double-blind, randomized trial introducing a sham control arm, designed to establish a significant difference in efficacy relative to placebo under controlled conditions. “Participants randomized to sham will have the opportunity to receive active bemdaneprocel if they wish at the end of the study,” he said.

The endpoints in the Phase III trial reflect an evolution in regulatory priorities. “Whereas a clinician-reported outcome was the primary efficacy endpoint in Phase I, exPDite-2 will utilize a patient-reported outcome, specifically the change from baseline in the Parkinson’s disease diary measure of ON-time without troublesome dyskinesia, adjusted for a 16-hour waking day,” Dr. Belfort shared. This approach was shaped in discussions with the FDA to better capture patient experience.

A Novel Cell-Based Approach to Improving Motor and Non-Motor Function

What sets bemdaneprocel apart is its unique characterization as the first allogeneic pluripotent stem cell-derived therapy for Parkinson’s. Rather than bathing the brain indiscriminately with dopamine, Dr. Belfort explained that bemdaneprocel is comprised of living cells that aim to integrate into local neural circuits providing regulated dopaminergic synaptic input to the specific brain regions that support normal motor function. He anticipates that this approach will both reduce motor symptoms and avoid causing side effects.

Beyond motor improvements, bemdaneprocel could also affect non-motor symptoms such as mood and social engagement, albeit indirectly. “A person with Parkinson’s disease who has significantly more ON-time without troublesome dyskinesia after receiving bemdaneprocel may be more inclined to integrate socially into their community, which could have positive effects on their mood,” he said.

Current therapies for Parkinson’s focus on dopamine replacement, but these often lose efficacy within three to five years and can cause intolerable side effects, particularly dyskinesia. Dr. Belfort shared that they are not aware of any treatments available now that are clearly neuroprotective, underscoring the urgent need for more robust, long-lasting interventions.

Meaningful Endpoints for Patient Quality of Life

FDA guidance has increasingly emphasized endpoints that reflect how a treatment changes patient experience, function, and survival. The exPDite-2 trial’s primary endpoint (i.e. change in ON-time without troublesome dyskinesia at 78 weeks) was chosen to align with this priority. “The diaries used in exPDite-2 are a patient reported outcome, and changes in the duration of ON-time without troublesome dyskinesia is considered an acceptable measure for improvement of motor function,” he said.

The trial also incorporates the MDS-UPDRS Part 2 scale, which quantifies activities of daily living, and the PDQ-39, a validated Parkinson’s disease-specific quality-of-life measure. Dr. Belfort is confident that a robust effect 78 weeks after a single dose would be impactful for patients.

Transforming the Care Paradigm for Parkinson’s Disease

If Phase III confirms bemdaneprocel’s efficacy and safety, the consequences for patient care could be dramatic. “If exPDite-2 demonstrates that bemdaneprocel is well tolerated and has a large beneficial effect compared to sham surgery, the treatment paradigm for Parkinson’s disease could change significantly,” said Dr. Belfort.

Unlike current therapies, bemdaneprocel seeks to restore regulated dopamine transmission to affected regions rather than simply masking symptoms. “If bemdaneprocel is able to reverse symptoms and provide years of improved motor function over what the current standard of care can provide, then we believe it will become a very important new drug for millions of people with Parkinson’s disease worldwide,” said Dr. Belfort.

Partnering with Bayer and the Pathway to Approval

As a wholly owned yet independently operated subsidiary of Bayer, BlueRock benefits from substantial resources and expertise. Dr. Belfort explained that Bayer has been instrumental in the conduct of the exPDite-2 study including supporting site activation, safety monitoring, and many other aspects. Should bemdaneprocel succeed, Bayer will lead commercialization efforts, as stipulated in the Arm’s Length agreement.

With exPDite-2 now underway and the first patient having been treated, BlueRock Therapeutics is at the forefront of developing a cell-based therapy that could redefine Parkinson’s disease management. The therapy’s ability to precisely target and restore dopamine signaling combined with its strong early safety data and robust partnership with Bayer may create substantial momentum for the next era in cell therapy. “If bemdaneprocel is able to reverse symptoms and provide years of improved motor function over what the current standard of care can provide, then we believe it will become a very important new drug,” said Dr. Belfort.