some comparison of trials

The advantages of drug PBT-2 have been discussed today in a couple of post.

It was mentioned that it is a superior drug than PBT-1; however the latter is not exactly a push-over either according to these comments:
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Date 16 Dec. 2003. Announcement, extract:

The study, performed through the Mental Health Research Institute in Melbourne (MHRI),
enrolled 36 patients who were assessed for indicators of cognitive performance such as memory, orientation, language, attention and reasoning using a cognitive score on the Alzheimer’s Disease Assessment Scale, the so-called ADAS-cog score.

The scores range from 0 to 70. A healthy normal adult has a very low score but as dementia progresses, the score increases.

Eighteen of the patients were assigned to placebo and 18 received Prana’s Alzheimer’s Disease drug, PBT-1, the first of Prana’s metal protein attenuating compounds (MPACs) to be developed for Alzheimer’s Disease.

PBT-1 is a chemical that binds zinc and copper, and has been shown to lower the levels of amyloid beta and the associated toxicity in the brains of transgenic mice used as a model of Alzheimer’s Disease.

+ + + + The more affected patients entering Prana’s pilot clinical trial (ie those with higher ADAS-cog
scores) showed an average deterioration in score at 24 weeks of about 1.5 points on PBT-1 and
about 8.9 on placebo, a difference of 7.4 in favour of PBT-1.

Generally, untreated patients with mild to moderate disease could be expected to gain six to 12 points in their ADAS-cog score over 12 months.

A panel convened by the Food and Drug Administration in the US deemed that an improvement of four points would be clinically significant.

“It is extremely encouraging to see findings like this in a clinical setting,” said Professor Colin Masters, a Director of Prana based at the University of Melbourne and the MHRI. Professor Masters jointly discovered the association between metals and aggregated proteins in the brains of patients with Alzheimer’s Disease.

“We designed the trial to detect only conspicuous effects on cognition, and that was exactly what
we were able to show. In addition, we showed decreased blood levels of amyloid beta, the major protein associated with plaques in the brain.

This is the first time any drug has been shown to
lower blood levels of this indicator of Alzheimer’s Disease,” he said.

Professor Masters added: “It is also heartening that the drug appears to be well tolerated. To date, ten patients who elected to continue taking PBT-1 at completion of the formal 36-week period of the trial have completed 18 months of treatment with no clinically significant adverse events attributable to the treatment”.

There is currently no cure for Alzheimer’s Disease. It is estimated to affect between 80,000 and 120,000 Australians, a figure that is likely to increase significantly with the ageing of the population .

+ + + + The most widespread treatment is a drug called Aricept that acts by improving the transmission of a particular type of nerve in the brain.

+ + + The clinical trials of Aricept showed a difference at 24 weeks of about three points between active treatment and placebo.

“This pilot Phase 2 trial has broad significance” said Geoffrey Kempler, Executive Chairman of
Prana Biotechnology. “Our technology platform is based on a proprietary understanding of the biochemistry and chemistry of protein-metal interactions and how these influence neurodegenerative diseases. This trial gives strong support to the use of our MPACs in further
trials ”
(end)
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This comparison of drug PBT-1 and drug "Aricept" is interesing and I have accentuated the relevant sections with + + + +.

Let us taske smaller sections and then we read:

+ + + The clinical trials of "Aricept" showed a difference at 24 weeks of about *three points* between active treatment and placebo.

+ + + + + + + + The more affected patients entering Prana’s pilot clinical trial (ie those with higher ADAS-cog
scores) showed an average deterioration in score at 24 weeks of about 1.5 points on PBT-1 and
about 8.9 on placebo, a difference of 7.4 in favour of PBT-1.

And that is using PBT-1. Now, let us have a go with the much more powerful drug PBT-2 later in the year.


Gerry