Please can you give an introduction to Prana’s IMAGINE trial of PBT2 in Alzheimer’s patients?
Approval for the IMAGINE trial was granted by the Austin Health Research Ethics Committee in November 2011, with the first patients dosed in March the following year. However, well before the trial was approved, PBT2 had already shown promise in significantly changing Abeta levels in spinal fluid while improving cognition in a previous 12-week trial conducted in 2006.
The 12-month IMAGINE trial really aims to cement PBT2’s credentials as a safe and effective treatment for Alzheimer’s disease, and the first treatment to target the cause of the disease, not the symptoms.
What are the aims of this study?
IMAGINE is a double-blind, placebo controlled Phase II clinical research trial to examine the effect of PBT2 on amyloid deposition in the brains of patients with prodromal or mild Alzheimer’s disease. For this study, we have a cohort of 41 patients aged 55 and over, who will take 250mg of PBT2 or a placebo once daily for 52 weeks.
The primary objective is to evaluate the effect of PBT2 on brain amyloid levels. Secondary to this, we want to evaluate the safety and tolerability of PBT2 by performing physical, neurological and optical examinations, vital signs, ECGs, haematology, biochemistry and urinalysis throughout the study. We will also measure the effect of PBT2 on brain metabolic activity and brain volume, particularly hippocampal and grey matter volume.
Finally, we will measure the effect of PBT2 on cognition as determined by a number of validated cognition questionnaires and its effect on everyday functional abilities.
How do you measure the effect of PBT2 on amyloid deposition in the brains of Alzheimer’s patients?
To evaluate the safety and tolerability of PBT2 and its effect on brain amyloid levels, we are using a brain scan called Positron Emission Tomography (PiB-PET). PiB is a chemical tagged with the radioisotope Carbon 11, which binds to amyloid and is scanned using PET to provide images of the brain.
How many participants have finished the full 12 months of treatment?
As of July, 15% of the 41 patients have now finished the full 12 months of treatment, while all have completed at least six months of dosing.
When do you expect to report the results of the IMAGINE trial?
Results from the IMAGINE trial are due for release in March. Currently we see no reason why that date would be extended.
The Austin Health Human Research Ethics Committee (HREC) has recently granted a year-long extension of Prana Biotechnology’s IMAGINE trial. What are the reasons behind this extension and what do you hope it will achieve?
Patients who have completed the full 12-month of dosing are eligible to participate in the open label extension study, where they will receive 250mg of PBT2 once daily for an additional 12 months. The first patient began dosing in July.
Approval from Austin Health was granted following a review of the potential benefits to patients and safety data collected during the IMAGINE trial. The opening label extension will be incredibly helpful as it will provide ongoing information to support the safety, tolerability and efficacy of PBT2 over a two year period.
PBT2 is also being tested in Huntington’s patients. Please can you tell us more about this?
Normally occurring metals the brain play a role in both Alzheimer’s and Huntington’s disease and researchers are now identifying ways to interrupt these interactions to prevent the deterioration of brain cells. Animal models of HD have indicated that PBT2 may be able to improve motor function and control, increase life span and reduce brain cell deterioration.
We are hopeful PBT2 can work in two ways against Huntington’s disease; prevent the accumulation of toxic huntintin proteins and the resultant damage inside neurons, and improve neuronal health and function by restoring normal copper and zinc levels which are disturbed when neurodegeneration takes place.
FDA approval to commence the Reach2HD trial of PBT2 in Huntington’s disease was granted in January last year and results from this Phase II trial are due in October this year.
Reach2HD is a six month trial in 109 patients with early to mid-stage Huntington’s disease, in 20 sites in the US and Australia. We are aiming to demonstrate safety, motor and behavioural benefits, and identify where patients could be showing a clinical benefit from PBT2. This will inform the design the next trial in the process of having PBT2 approved for marketing.
What are Prana’s plans for the future?
Prana has a pipeline of products we are very excited about; It’s part of what makes Prana such a unique company in that we don’t have a single product we are pinning our hopes to.
PBT2 is in Phase II testing for AD and HD, however, we have another compound, PBT434, which is targeted at movement disorders, including Parkinson’s disease and Atypical Parkinson’s diseases, which is currently in the preclinical toxicology stage but is on track to start clinical trials in 2015. In June, new data presented at a the 17th Annual Congress of Parkinson’s disease and Movement Disorders in Sydney showed PBT434 had significant disease-modifying capability in multiple animal models of Parkinson’s disease and has potential utility in a range of other movement disorders.
PBT434 has two major benefits. First, it prevents cell death by inhibiting the interaction between dopamine and iron, and secondly stops the accumulation of alpha synuclein in the brain.
Another compound, PBT519, is in very early preclinical screening as a treatment for brain cancer. The other exciting part of our portfolio is that we have a library of more than 900 other compounds under research.
Where can readers find more information?
All our press releases are lodged to the Australian Stock Exchange (ASX) and our website, which we will be re-launching later this year with a new look and new features. We thought it was time for an overhaul!
About Geoffrey Kempler
Mr Kempler has served as Chairman of the Board of Directors since November 1997, and served as Chief Executive Officer from November 1997 to August 2004. He assumed the position of Chief Executive Officer in June 2005.
A qualified psychologist, Mr Kempler is one of the founders of Prana and has extensive experience in investment and business development. He has managed Prana’s operations to date and is responsible for the implementation of Prana’s strategic plan and the commercialization of its technology.
Mr. Kempler holds a B.Sc degree in science from Monash University and Grad. Dip. App. Soc. Psych. degree from Swinburne University.
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