Seth Ettenberg, BlueRock Therapeutics CEO
August 28, 2023 02:00 AM EDTUpdated 06:17 AM R&D
BlueRock, Bayer’s stem cell group, details glimpses of efficacy in Parkinson’s disease therapy
Ryan Cross
Senior Science Correspondent
A treatment that aims to restore the damaged and dying brain cells that cause uncontrollable movements in Parkinson’s disease is showing promising, albeit early, signs of being safe and effective.
BlueRock Therapeutics, Bayer’s stem cell therapy subsidiary, on Monday revealed the first detailed look at the results from a Phase I trial of bemdaneprocel, a therapy made from lab-grown neurons surgically implanted in the brains of 12 patients with Parkinson’s.
In an interview ahead of the company’s presentation at a Parkinson’s meeting in Copenhagen, BlueRock CEO Seth Ettenberg told Endpoints News that the company hoped to answer three questions with the study: Would the cells engraft after implanting them in a patient’s brain? Would the treatment be safe enough to justify the invasive procedure? And was there any indication that it helped patients?
Earlier this summer, the company announced that the treatment was safe enough to begin planning for a larger study. BlueRock disclosed that one patient temporarily developed seizures a day after the surgery, although the cells themselves did not cause any serious side effects. That 70-year-old man recovered after receiving medication and hasn’t had any seizures since, Ettenberg said.
One year after the surgery, the seven patients who got the high dose of the therapy had a 13-point reduction on a scale that doctors use to measure the motor symptoms of Parkinson’s, and the five patients who got a low dose had a 7.6-point reduction. A 5-point reduction has historically been considered clinically significant. Patients receiving the high dose also cut their time spent with uncontrollable movements — so-called “off time” — each day by about 2 hours.
“We saw an almost around 50% decrease in their off time, which means they’re gaining control of those movement disorders,” Ettenberg said. “If we were writing the script two years ago, this is what we would be hoping for. We’ve gotten everything we need to move this to Phase II.”
Glimpses of safety and efficacy
BlueRock is among the most prominent biotechs in the early stages of developing new stem cell-derived therapies. Rather than injecting stem cells directly into a patient, the company grows its stem cells into dopaminergic neuronal precursor cells in the lab before a surgeon implants them into each side of a patient’s skull.
The goal is to help rebuild the network of dopamine-producing cells in a brain region called the putamen, which is vital for controlling movement but is damaged in Parkinson’s disease. The patients in the study were diagnosed with the condition nine years earlier, on average. And although they were still getting some benefit from levodopa — essentially a dopamine replacement that is the standard of care — all started to lose the full benefit of the treatment over time.
Most of the mild and moderate adverse events were related to immunosuppressant drugs that patients took for one year after the surgery, Ettenberg said. There were no serious adverse events related to the cell therapy, he added, and the seizures one man developed were “somewhat expected for us, and for the field, given that you’re passing a cannula into each side of the brain.”
Since no one got a placebo in the study and there was no control arm, Ettenberg was careful to note that this study was not a true test of the therapy’s effectiveness. “It’s not powered to speak to the clinical benefit here. But of course, we’re all interested in that. And the patients are interested in that. And we need to speak to it,” he said.
The randomized placebo-controlled Phase II trial will seek to more strongly answer questions about the treatment’s efficacy and durability. “We’re still in discussion with the FDA of exactly what that trial design would look like,” Ettenberg said.
Stem cell sources
Much of the excitement around stem cells is centered on the Nobel Prize-winning discovery that enables scientists to turn skin cells or other easily obtainable cells from adults into so-called induced pluripotent stem cells, or iPSCs.
These iPSCs partly resemble embryonic stem cells that can be turned into any other cell but with fewer ethical quandaries, and therapies made from iPSCs are only beginning to move from the lab bench and into the clinic. BlueRock’s treatment was made from a cell line that originally came from embryos — fertilized eggs that were never implanted in a patient.
Ettenberg said academic work on those cells started in 2009, three years after iPSCs were made in a petri dish for the first time. Using embryonic stem cells “was the fastest” way forward, he said, adding that there was no fetus involved in making the stem cells, and that the company can perpetually generate new cells from the ones they already have.
“All of the source for this material is already in the freezer. And we will never go back and create another source for that,” he said. “It’s what attracted me to this field in general. You’re making a reproducible, reliable, indefinite source of this material, which can become more drug-like in its characteristics.”
The Parkinson’s treatment is BlueRock’s most advanced program, though the rest of the company’s earlier-stage work focuses on therapies made from iPSCs. BlueRock is getting ready for a Phase I clinical trial with Opsis Therapeutics, a subsidiary of Fujifilm, to make retinal cells for inherited vision diseases. Another program focused on making cardiomyocytes — heart muscle cells — is close behind.
Earlier this month, BlueRock laid off about 50 employees, and Ettenberg said the cuts were expected to help tighten the company’s focus on the next phase of its Parkinson’s program and upcoming retinal disease treatment.
AUTHOR
Ryan Cross
Senior Science Correspondent
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