First Patient Dosed in Phase 2 Trial of Bryostatin-1 in Long-term Use

A first patient has been dosed in a Phase 2 trial investigating the safety and long-term efficacy of bryostatin-1 in treating moderate and moderately severe Alzheimer’s disease, the therapy’s developer, Neurotrope, announced.

The trial (NCT04538066), which is recruiting patients at several sites across the U.S., will build on data from previous studies assessing bryostatin-1. Specifically, it is looking at the investigative therapy’s long-term effectiveness on aiding cognition in people not using Namenda (memantine), an approved Alzheimer’s treatment marketed by Allergan.

The study, which opened this year, aims to enroll about 100 patients with moderate and moderately severe Alzheimer’s, as measured by the mini-mental state examination (MMSE-2). Those enrolled will be randomly assigned to either bryostatin-1 or a placebo — both in the absence of Namenda — for two 11-week dosing cycles, given over six months.

Its main goal will be to assess the long-term effects of bryostatin-1 on patients’ cognitive function, as measured by the Severe Impairment Battery (SIB), a test used to assess cognition in people with advanced dementia who are unable to complete other psychological tests.

SIB scores here will be calculated after the completion of both treatment cycles, at week 28, and compared to scores recorded at the study’s start in both patient groups.

As secondary efficacy endpoints, these scores will also be determined periodically throughout the trial, as well as at the last study visit at week 42.

“Dosing the first patient in our Phase 2 study of Bryostatin-1 in AD [Alzheimer’s disease] is an important milestone for Neurotrope, and we remain grateful for the ongoing support and validation from the National Institute on Aging at the NIH,” Josh Silverman, chairman of the board of Neurotrope, said in a press release.

“AD remains among the most significant public health challenges of our modern era and, with support from the NIH, we hope to deliver progress toward advancing a new and innovative, disease modifying treatment,” Silverman added.

Bryostatin-1 is a molecule that is designed to cross the blood-brain barrier — the semi-permeable barrier that separates and protects the brain from the circulating blood — and to increase the activity of the enzyme protein kinase C (PKC) in brain cells. Evidence suggests PKC activity is linked to cognitive function, and required for the maintenance of healthy synapses — the sites where nerve cells come into contact and communicate with each other.

A previous Phase 2 trial (NCT02431468), assessing the efficacy of two doses of bryostatin-1 in 147 patients with moderate to severe Alzheimer’s, showed the therapy’s lowest dose (20 micrograms, mcg) was safe and led to improvements in cognitive function. This benefit was seen to be more pronounced in a subgroup of patients not taking Namenda.

In those with moderately severe disease, improvements in cognition were sustained for four weeks after the end of treatment.

A follow-up Phase 2 trial (NCT03560245), assessing an 11-week treatment course of 20 mcg of bryostatin-1 without Namenda, showed treatment led to similar cognitive improvements in patients with moderately severe disease. However, the study failed to meet its primary efficacy goal of demonstrating bryostatin-1’s superiority over a placebo at improving cognitive function in those with more severe disease.

“After reviewing data from previous trials of Bryostatin-1 with both key opinion leaders and the NIH, we determined that a study to evaluate its long-term therapeutic effects in the absence of Namenda in patients with AD was a priority,” said Daniel Alkon, MD, president and chief scientific officer of Neurotrope.

“We have made rapid progress in commencing this study, and are very pleased to announce today that the first patient has been dosed after significant progress in patient enrollment,” Alkon added.

The new Phase 2 trial is being supported by a $2.7 million grant issued by the U.S. National Institutes of Health (NIH). It is also being supported by the National Cancer Institute, which is providing the natural source of bryostatin that will be used in the study.