Neurotrope Announces Publication of Phase 2 Alzheimer's Study

Neurotrope Inc. announced that data from its Phase 2, multidose, exploratory trial evaluating Bryostatin-1 as a treatment of cognitive deficits in moderate to severe Alzheimer's disease were published online in the Journal of Alzheimer's Disease. 

The double-blind, placebo-controlled, Phase 2 trial, which was completed in May 2017, randomized patients 1:1:1 into 20 μg Bryostatin-1, 40 μg Bryostatin-1, and placebo arms. This peer-reviewed article provides what we believe is the first comprehensive data presentation of the Phase 2 trial of a drug with a new mechanistic approach for advanced AD. 

"Neurotrope's Phase 2 trial of Bryostatin for advanced Alzheimer's patients has shown promising positive signals of improvement," said Dr. Marwan Sabbagh, MD, director of the Cleveland Clinic Lou Ruvo Center for Brain Health. "This drug's observed sustained reversal of cognitive deterioration is consistent with the restorative, synaptogenic findings that Dr. Alkon and his teams have described during the years of pre-clinical research that preceded this potentially breakthrough clinical approach for treating neurodegeneration."

"Therapeutic strategies for AD have focused on immunotherapy, and enhancement or blockade of neurotransmitters at synaptic junctions, approaches which may offer some symptomatic efficacy but have not demonstrated the ability to reverse the relentless progression of AD," said Dr. Martin R. Farlow, MD, Professor Emeritus in the Department of Neurology at Indiana University and co-director of the Alzheimer's Disease Center at Indiana University. "Preclinically, Bryostatin-1 has demonstrated the ability to restore synaptic loss, prevent neuronal apoptosis, reduce A Beta oligomers, lower hyperphosphorylated tau and reduce oxidative stress.  These Phase 2 results show the early promise of translating this preclinical work, supported by years of research at the NIH and Blanchette Rockefeller Neurosciences Institute, into clinical outcomes.  I look forward to seeing them expanded upon in further ongoing studies."

The study was designed to assess the safety and efficacy of Bryostatin-1 as a treatment of cognitive deficits in patients with moderate to severe AD (n=147).  Patients enrolled in the study were allowed to continue on background therapy, including cholinergic and/or anti-glutamatergic treatment.  These therapies are known to yield symptomatic efficacy, but their effect has not been shown to treat underlying disease progression.  The primary efficacy analysis for this Bryostatin-1 trial was change in Severe Impairment Battery (SIB) scores. For patients in the 20 µg Bryostatin-1 dose group (n=49, with 38 completers), SIB scores were greater than baseline, indicating persistence of improvement in cognitive function. A pre-specified ANCOVA for baseline memantine interaction with Bryostatin-1 and positive post-hoc trend analyses were statistically significant.

The magnitude of improvement was greater in a pre-specified exploratory analysis of patients not on memantine therapy (n=16).  Analyses of patients in this group showed evidence of sustained SIB improvement over baseline compared to placebo patients not on memantine (> 6.30 points, 8.4 points when compared to all placebo). Individual patient SIB scores over time revealed that 15 out of 16 patients (94%) in the 20 μg Bryostatin-1, non-memantine group showed improvement in SIB at 2 – 4 weeks post-dosing. For placebo patients and for patients on baseline memantine, there were no consistent increases in SIB measures over time. In addition, the safety profile was similar for patients treated with 20 μg Bryostatin-1 and placebo.

"We believe the findings of this exploratory trial suggest that the neurorestorative potential for Bryostatin-1 to generate new, mature synaptic connections and prevent neuronal death could potentially lead to a meaningful reversal of disease progression," stated Dr. Daniel Alkon, president and chief scientific officer of Neurotrope. "For patients receiving 20 μg Bryostatin-1 and no background memantine therapy, the totality of these analyses suggest that the trial showed evidence of Bryostatin-1's SIB improvement signals.  These promising exploratory Phase 2 results support further trials of 20 μg Bryostatin-1, without memantine, to treat AD. A confirmatory Phase 2 clinical trial, in patients with moderate to severe AD, is well underway, and we look forward to the results in the coming months."

Neurotrope is currently evaluating Bryostatin-1 (20 µg) in 100 moderate to severe AD patients not on memantine in a confirmatory, placebo-controlled, Phase 2 trial, initiated in July 2018.  Enrollment is proceeding as planned, and data from this study are expected during the third quarter of 2019.