The company expects to dose the first patient later this year.
“We are very excited to advance Bryostatin-1 to its next phase of development,” Daniel Alkon, MD, president and chief scientific officer of Neurotrope said in a press release.
Bryostatin-1 is a small molecule designed to penetrate the blood-brain barrier and specifically activate the protein kinase C, which plays an important role in learning and memory, and in maintaining the health of synapses — junctions where nerve cells come into contact and communicate with each other.
The new Phase 2 clinical trial intends to enroll approximately 100 patients with moderate and moderately severe Alzheimer’s disease, as measured by Mini-Mental State Exam scores.
“Conducting a clinical trial longer in duration may help address some of the placebo effect seen in earlier studies,” said Marwan Sabbagh, MD, director of Cleveland Clinic Lou Ruvo Center for Brain Health.
The trial will focus on evaluating sustained cognitive benefit measured by the Severe Impairment Battery (SIB) score — a test designed to assess cognitive function in people with dementia who are unable to complete other psychological tests. Higher scores indicate better functionality (i.e., less evidence of dementia).
The study will be conducted in partnership with the National Institutes of Health, who has awarded nearly $2.7 million in funding to Neurotrope.
“Given the high unmet need for new therapies to treat [Alzheimer’s disease], recognized by the NIH and highlighted by their financial and scientific support, we plan to move this program forward as rapidly as possible, with the goal of demonstrating Bryostatin-1’s potential benefit in this setting,” Alkon said.
The effects of bryostatin-1 on cognition have been tested in a previous Phase 2 trial (NCT02431468), which enrolled 147 patients with moderate-to-severe Alzheimer’s disease. Participants were randomly assigned to receive bryostatin-1 at 20 or 40 microgram (mcg) doses, or a placebo, administered intravenously (into the vein) every other week for 12 weeks.
Bryostatin-1 was seen to be safe and have a good tolerability profile. SIB scores showed that only patients treated with 20 mcg doses of bryostatin-1 had sustained improvements in cognitive function compared to the placebo group.
In that trial, patients with moderately severe Alzheimer’s improved their SIB scores by 5.0 from the start of the study, which persisted for four weeks after treatment was completed.
A subsequent Phase 2 trial (NCT03560245) enrolled 108 patients with moderate-to-severe Alzheimer’s disease who were randomly assigned to receive 20 mcg of bryostatin-1 or a placebo, given intravenously every other week for 12 weeks.
In this trial, a similar improvement in SIB scores was seen for patients with moderately severe Alzheimer’s. However, from the trial’s start, the average SIB score for patients of all disease severities had increased by 1.3 points in the bryostatin-1-treated group compared to a 2.1-point increase in the placebo group. This meant that the trial failed to meet its primary goal of lesser evidence of dementia in people with more severe disease.
In these earlier trials, patients with moderate and moderately severe Alzheimer’s were seen to benefit the most from bryostatin-1 treatment (in contrast to those with more severe disease).
“Central to this new development effort is to study Bryostatin-1’s efficacy over a longer course of treatment and in patients whom we believe show the most potential for clinical benefit,” Alkon said.
“We believe that the valuable insights gained from our previous studies have provided crucial guidance for our next trial to increase the possibility of observing clinically meaningful benefits for Alzheimer’s patients with concrete evidence of dementia, benefits that may also possibly translate to MS [multiple sclerosis], stroke and Fragile X, as preclinical studies suggest,” he added.
Neurotrop has engaged Worldwide Clinical Trials to start site recruitment and activation for the trial.
The company has also entered into a definitive merger with Metuchen Pharmaceuticals, which will result in a newly formed company named Petros Pharmaceuticals. After the merger is complete, bryostatin-1 and other Neurotrope holdings will be spun out into a new, separately traded company named Neurotrope Bioscience.
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