Second Phase 2 Trial of Byrostatin-1 for Alzheimer Disease Treatment Planned

Data has been reported from a phase 2 confirmatory clinical trial (NCT03560245) of bryostatin in individuals with moderately severe to severe Alzheimer disease (AD), who were not treated with concomitant memantine.

There was a statistically significant improvement over baseline in the mean severe impairment battery (SIB) at week 13 for subjects in the bryostatin-1 treatment group, 32 participants, paired t-test P<.0076, 2-tailed. As a further test of the robustness of this moderate stratum benefit signal, a pre-specified trend analysis, measuring increase of SIB improvement as a function of successive drug doses, was performed on the repeated SIB measures over time (Weeks 0, 5, 9, and 13).  These trend analyses showed a significant positive slope of improvement for the treatment groups in the study that was significantly greater than for the placebo group (P<.01).

In the placebo group (n= 33), there was also a statistically significant increase from baseline in the mean SIB at week 13, for paired t-test P<.0144, consistent with the placebo effect seen in the overall 203 study. "This smaller, placebo effect could possibly be due to the imbalance observed even for the moderate stratum in the study," stated Dr. Alkon. For the prespecified severe stratum (MMSE-2 baseline scores 4 – 9) participants, there was no statistically significant change from baseline for either the treatment or the placebo group.  

"A significant imbalance (4.8 points) in the baseline SIB scores occurred, by chance, between the bryostatin-1 treatment group and placebo group," stated Dr. Daniel Alkon, Neurotrope's president and chief scientific officer.  "After consulting with our Scientific Advisory Board and statistical experts, we were advised that, in a small study such as this, a baseline imbalance could prevent a definitive analysis of Bryostatin-1 treatment versus placebo in SIB scores at the primary (Week 13) and secondary endpoints as provided in the original statistical analysis plan (SAP)," stated Dr. Alkon. 
$2.7 million was awarded from the National Institute of Health (NIH) to support an additional phase 2 clinical study focused on the Moderate Stratum for which the Company saw improvement in the 203 study. The Bryostatin program is planning to meet with the Food and Drug Administration to present the totality of the clinical program data for Bryostatin-1.

"Due to the baseline imbalance observed in the study, and because a clear signal of benefit could be observed in the raw data from the prespecified moderate stratum, we conducted a posthoc analysis using paired data for individual patients, with each patient as his/her own control," stated Kazem Kazempour, chief executive officer of Amarex,  the biostatistician retained to analyze the data under the SAP.  

For the prespecified moderate stratum, the baseline value and the week 13 value were used, resulting in pairs of observations for each patient. The changes from baseline for each patient were calculated and a paired t-test was used to compare the mean change from baseline to week 13 for each participant. A total of 65 participants had both baseline and week 13 values, from which there were 32 participants in the Bryostatin-1 treatment group and 33 participants in the placebo group.