Charles S. Ryan, JD, PhDCharles S. Ryan, JD, PhD
Neurotrope has announced that its phase 2 study of Bryostatin-1, an investigational treatment for moderate to severe Alzheimer disease (AD), did not meet its primary end point of change from baseline to week 13 in Severe Impairment Battery (SIB) total score.1

The novel therapeutic, a potent activator of protein kinase C epsilon, has demonstrated benefits for synaptic loss and maturation in animal models of AD, as well as other neurological disorders including stroke and Fragile X syndrome.2

The phase 2, randomized, placebo-controlled, multi-center trial sought to assess the safety, efficacy, and tolerability of intravenous Bryostatin-1 20µg in 108 participants with AD who were not taking memantine (NCT03560245). Participants were randomly assigned 1:1 to Bryostatin-1 or placebo for 12 weeks for a total of 7 doses. Secondary end points included evaluated of change from baseline in SIB total score across weeks 5, 9, 13, and 15 among patient groups stratified by Mini Mental State Exam-2. Participants were aged 55 to 85 and had to have been off treatment with memantine for at least 30 days prior to initiation of the study drug.

At week 13, an average increase in SIB total score of 1.3 and 2.1 points was observed in the Bryostatin-1 and placebo groups, respectively. No statistically significant differences in change from baseline were observed across other weekly time points between the treatment and placebo groups.

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"We are disappointed in the topline results from the confirmatory Phase 2 study," said Charles S. Ryan, JD, PhD, Neurotrope's chief executive officer, in a statement.1 "Having just received the data, we are conducting a full review to determine potential next steps and will provide an update of our plans when appropriate.”

Previous results of a dose-finding phase 2 study published in the Journal of Alzheimer’s Disease did demonstrate a potential reversal of disease progression in patients treated with the drug, though statistical significance was still not achieved.3

While the fate of bryostatin-1 in AD is unknown, Neuotrope is continuing preclinical studies of the drug in multiple sclerosis, stroke, Niemann-Pick type C, Rett syndrome, traumatic brain injury, and Fragile X syndrome, for which it was granted orphan drug designation by the FDA.
1. Neurotrope Announces Top-line Results From Confirmatory Phase 2 Study of Bryostatin-1 in Moderate to Severe Alzheimer's Disease [news release]. New York, NY: Neurotrope, Inc. September 9, 2019. Accessed September 9, 2019.
2. Nelson TJ, Sun MK, Lim C, et al. Bryostatin effects on cognitive function and PKCɛ in Alzheimer's disease phase IIa and expanded access trials. J Alzheimers Dis. 2017;58(2):521-535.
3. Neurotrope Announces Publication of Phase 2 Study of Bryostatin-1 in Moderate to Severe Alzheimer's Disease in the Journal of Alzheimer's Disease [news release]. New York, NY: Neurotrope, Inc. December 17, 2018. Accessed September 9, 2019.