1st Patient Dosed With Bryostatin as Developer Seeks Best Regimen
The first patient has been dosed in an open-label dose optimization trial of bryostatin, an investigational treatment for Alzheimer’s disease.
According to the therapy’s developer, Synaptogenix — previously called Neurotrope — the dose-finding trial will prepare the company to move forward with bryostatin’s next phase of clinical development.
The therapy is designed to improve cognitive function in people with moderate to severe Alzheimer’s.
The announcement comes on the heels of recently published pooled data from two pilot placebo-controlled Phase 2 trials: NCT02431468 and NCT03560245. Together, these trials cumulatively evaluated the effects of bryostatin against a placebo over three months in 255 people whose Alzheimer’s was moderate to severe.
Bryostatin in clinical trials
Data from the publication indicated that a 12-week course of intravenous (into-the-vein) bryostatin at a dose of 20 micrograms (mcg) led to a statistically significant improvement in cognition. Such an effect was not seen in the placebo group among patients with moderate disease who were not using Namenda (memantine), an approved medication for Alzheimer’s.
“While the current dosing has been found to produce clear cognitive improvement over baseline, the company has planned a dose-ranging study to optimize the extent and duration of benefits,” Daniel Alkon, MD, president and chief scientific officer of Synaptogenix, said in a press release.
“With the encouraging data reported in our recent article, we want to be well positioned to conduct a registration study and to enter the clinic as soon as possible,” Alkon added.
Bryostatin is a molecule designed to increase the activity of the protein kinase C (PKC) enzyme in brain cells. Evidence suggests that PKC activity may be involved in cognitive function, and is required for the maintenance of synapses — the sites where nerve cells communicate with each other. It’s thought that the medication may be able to protect against the loss of synapses seen in Alzheimer’s disease, thus improving cognitive function.
An ongoing Phase 2b clinical trial (NCT04538066), which began dosing in October 2020, is investigating the long-term efficacy of bryostatin against a placebo in about 100 people with moderate Alzheimer’s. These individuals, who are not using Namenda, are the subset of patients who appeared to benefit most in the earlier pilot trials.
Participants will receive seven doses of intravenous bryostatin (20 mcg) or a placebo during the first 12 weeks (about three months). A second seven-dose course will begin 30 days after the final dose in the first treatment period.
Cognitive tests will be administered throughout the study, and for four months after the final dose. In addition to safety, the study’s primary efficacy goal is to assess changes in the Severe Impairment Battery (SIB) score between the study’s start and at week 28 — after both rounds of treatment.
The SIB is an assessment of cognition in people with moderate to severe Alzheimer’s and encompasses facets of cognition including attention, language, orientation, memory, sensory processing, and social skills. The test allows for nonverbal responses, making it easier to use for individuals with limited verbal abilities.
As secondary goals, SIB scores also will be determined periodically throughout the trial, and at the last study visit at week 42, or just before 11 months.
Enrollment in the trial is complete and clinical testing is ongoing, according to Synaptogenix. Topline data from the trial, which is sponsored by the National Institutes of Health, is expected in the last quarter of 2022.
“We continue to believe Bryostatin is uniquely positioned to target synaptic loss and are looking forward to announcing a read out of our Phase 2 topline data later this year,” said Alan Tuchman, MD, CEO of Synaptogenix.