Neurotrope announced the first patient has been enrolled into its confirmatory Phase 2 clinical trial with its lead Alzheimer's disease drug, Bryostatin-1. Patient recruitment will take place at approximately 30 clinical sites in the United States. This follow-on confirmatory clinical trial is planned to include 100 patients with moderate to severe Alzheimer's disease (AD) (defined as a Mini Mental State Exam 2 score of 4-15). Patients will be randomized 1:1 to be treated with either Bryostatin-1 20ug or placebo, receiving 7 doses over 12 weeks. Patients on memantine, an NMDA receptor antagonist, will be excluded unless they have been discontinued from memantine treatment for a 30-day washout period prior to study enrollment. The primary efficacy endpoint is the change in the Severe Impairment Battery (SIB) score between the baseline and the average of weeks 13 and 15. In the previous Phase 2 trial, patients in the bryostatin 20ug dose group not receiving concurrent memantine treatment exhibited a SIB score improvement from baseline of over 6 points. There was no corresponding treatment effect for memantine-treated patients. Both bryostatin and memantine, an N-Methyl-D-aspartate (NMDA) receptor antagonist, engage the NMDA receptor. This convergence of memantine and PKC on the NMDA receptor may explain why patients who were not taking memantine during the trial exhibited a consistent cognitive improvement as measured by the SIB. In the absence of memantine, which blocks the NMDA receptor, bryostatin-activated PKC epsilon contributes to the regulation of this receptor.
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"The potentially important persistence of the bryostatin-induced improvement in the SIB scores in our recently completed Phase 2 trial, even one month after completion of all dosing, is an effect that we hope to repeat in this confirmatory trial. Immunologic A Beta degradation has recently been the target of Biogen trials that appear to reduce the rate of cognitive decline in prodromal and early AD patients. Bryostatin's mechanism also contributes to the elimination of A Beta oligomers and amyloid plaques through activation of brain A Beta degradation enzymes. In addition, we believe the persistent reversal of cognitive decline in advanced AD patients may result from the multi-modal efficacies of bryostatin that include growth of new synapses and prevention of neuronal death. In late-stage AD patients in our Phase 2 trial, bryostatin appeared to cause an increase in cognition – i.e. sustained improvement of SIB scores over baseline. Bryostatin's sustained cognitive improvement is consistent with a long-lasting consequence of PKC epsilon-growth factor effects that could induce the growth and/or maturation of synaptic networks in the brain. Our hope is that this might translate into long lasting cognitive function benefit in advanced AD patients, and earlier stage patients," said Dr. Daniel Alkon, Neurotrope's President and Chief Scientific Officer.
"Since February 2018, when I joined Neurotrope, I have reviewed a more extensive data set from the previous Phase 2 trial that gives me even more confidence that bryostatin had a positive effect on the patients in that study. I have also been receiving very positive feedback from key opinion leaders and I am very encouraged that this confirmatory Phase 2 study is initiating," said Dr. Charles Ryan, Chief Executive Officer of Neurotrope.