Optimism Surrounds Highly Anticipated PBT2 Alzheimer's Trial
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EmailMelbourne - Prana Biotechnology announced that it has received approval from the Austin Health Research Ethics Committee to commence a 12 month Phase II Imaging trial testing PBT2, the Company’s drug in development for Alzheimer’s Disease.
The purpose of the trial, which builds on the success of an earlier Phase IIa clinical trial of PBT2, is to measure physical changes in the brains of participants treated with PBT2 for 12 months, and to consolidate the evidence, over a longer period, of the positive effects of PBT2 on patients’ cognition reported in the earlier trial.1,2
“This is an important milestone for the Company. Given that PBT2 has already been shown both to significantly change A-beta levels in spinal fluid and improve the cognition of Alzheimer’s Disease patients in a 12 week trial, we believe that in this 12 month trial PBT2 will establish its credentials as a safe and effective treatment for Alzheimer’s Disease”, commented Prana’s Executive Chairman, Mr Geoffrey Kempler.
The double blind placebo controlled trial will enroll 40 patients with prodromal or mild Alzheimer’s Disease in 3 sites in Melbourne, Australia. Brain Imaging will be used to measure PBT2’s effect on amyloid deposits in the brain (using PiB-PET scanning) and
effects on increasing brain activity (F-FDG PET). Cognition effects will be measured by the Neuropsychological Test Battery (NTB). The protocol synopsis appears below in Appendix 1.
Funding and Key Opinion Leader support
The trial has received funding from the Alzheimer’s Drug Discovery Foundation (ADDF). Howard Fillit, MD, the ADDF’s Executive Director commented that “PBT2 stands out as one of the few remaining orally available agents with clinical trial evidence of cognitive benefit for Alzheimer’s patients.3 Success in this trial will demonstrate target engagement by PBT2 in the brain of people with Alzheimer’s Disease, and accelerate the clinical development of PBT2 to patients”.
Commercial Strategy
AD and dementia affects over 26 million people worldwide. The cost to society has been reported as $600 billion per annum. Currently all available treatments are approved to provide some degree of symptomatic relief. None change the course of the disease and the eventual decline in patient’s cognition and health. Over the past few years several high profile Phase III trials have failed to reach their primary endpoints. PBT2 has the potential to be an effective treatment for AD that is supported by an extensive body of scientific and clinical work. Prana’s earlier clinical data was for a 12 week trial in 78 patients, the new PBT2 Imaging Trial provides the opportunity to treat patients for 12 months, providing significantly more safety data as well as efficacy data. The study design aims to demonstrate PBT2’s potential as an effective disease modifying treatment available to patients.
Previous Clinical Evidence
Patients with mild AD treated with 250mg of PBT2 (a once-a-day capsule) demonstrated a significant improvement in cognition (NTB Executive Function Composite z-score, p=.042). The effect was noteworthy because of the sample size of patients on the effective dose (n=27) and the period of treatment (12 weeks). The new PBT2 Imaging Trial will have the same number of patients treated with the same effective dose (n=27) but for the much longer period of 12 months. The clinical data from earlier trials can be viewed here.
Strong Scientific Evidence
The scientific data supporting the belief that PBT2 will bring meaningful clinical benefit to patients is extensive. A position paper on PBT2’s mechanism of action can be viewed here. PBT2 restores neuronal health by selectively binding and redistributing brain metals (copper, zinc) that have become imbalanced due to disease or the ageing process. The positive effects on brain function delivered by PBT2’s actions are:
1. Anti amyloid effects:
- Reduces Abeta Aggregation4
- Promotes Dissolution of Abeta Oligomers4
- Prevents toxicity of Abeta oligomers (preventing binding to NMDA receptors)4
- Promotes Abeta Degradation and Clearance4,6
- Redistributes Abeta-Sequestered Metals back into neurons and other cells4,6
2. Neuroprotective and neurotrophic effects
- Redistributes metals into neurons and modulates intracellular signalling pathways4,6
- Reduces potential for glutamate excitotoxicity
- Restores Synaptic Plasticity (LTP and Spine Density) ie promotes neuronal regrowth4,5
- Prevents free radical production (silences redox activity of redox active metals)4
- Reduces tau hyperphosphorylation5
Appendix 1
Protocol synopsis
| Title | A randomised, double-blind, placebo-controlled study to assess the safety and tolerability of PBT2, and its effect on amyloid deposition in the brains of patients with prodromal or mild Alzheimer's disease |
|---|---|
| Study Number | PBT2-204 |
| Study Design | Randomised, double-blind, placebo-controlled, Phase IIa study |
| Objectives |
Primary Objective
Secondary Objectives
|
| Number of Patients | It is planned that 40 patients will be randomised in to the study |
| Key Patient Criteria |
|
| Doses | Placebo (0mg PBT2) and 250mg PBT2, once daily capsules |
| Per Patient Duration | 60 weeks: Four week Screening period, 12 months (52 weeks) Treatment period and Follow-up 4 weeks post treatment |
| Endpoints |
Primary
Secondary
|
| Trial Locations | Approximately 3 sites in Melbourne, Victoria |
| Trial Standard | Study will be conducted according to ICH GCP |
Related Videos & Articles
More Information
Links:
1. Lannfelt et al. “Safety, Efficacy, and biomarker findings of PBT2 in targeting Abeta modifying
therapy for Alzheimer’s disease: a controlled phase IIa, double-blind, randomized, placebocontrolled trial”, Lancet Neurology (2008) vol. 7, pp. 779-86.
2. Lannfelt et al. Errata: Lancet Neurology (2009) vol. 8, pp. 981.
3. Faux et al “PBT2 Rapidly Improves Cognition in Alzheimer's Disease: Additional Phase II Analyses”, Journal of Alzheimer’s Disease (2010) vol. 20 pp. 509-516
5. Crouch et al. “The Alzheimer’s therapeutic PBT2 promotes amyloid-B degradation and GSK phosphorylation via a metal chaperone activity”, Journal of Neurochemistry (2011) vol. 119, pp.220- 230
About Prana Biotechnology Limited
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