MELBOURNE, Australia,
July 17, 2014 /PRNewswire/
-- Prana Biotechnology (NASDAQ: PRAN; ASX: PBT) has today
provided an update on its clinical development program for
Alzheimer's disease.
Professor Colin Masters, the
Florey Institute of Neuroscience and Mental Health, The
University of Melbourne, will today
include data from Prana's Phase 2 IMAGINE and EURO trials in his
presentation at the Alzheimer's Association International
Conference in Copenhagen,
Denmark.
The presentation is entitled: "How to change and monitor the
rates of ABeta amyloid accumulation and cognitive decline in
Alzheimer's disease". The presentation can be viewed here: AAIC
Panel Presentation_Colin Masters
The IMAGINE trial top-line draft results were released on
31 March 2014. Further sub-analyses
of the top line imaging data have been performed, including
PiB-PET, MRI and FDG analysis of the effects of a once daily, 250
mg dose of PBT2 over 12 months. IMAGINE enrolled 42 patients, 27 in
the PBT2 group and 15 in placebo.
The primary objective of the IMAGINE trial was to explore
whether amyloid burden, as measured by PiB-PET would decrease in
participants treated with PBT2 relative to placebo. However, in
contrast to published literature, the average amyloid burden in the
placebo group fell during the trial.
Prana conducted a sub-analysis to better understand the
behaviour of the placebo group and what can be learned in the trial
about the utility of such exploratory biomarkers for future
trials.
In Professor Masters' presentation, he noted that the starting
amyloid burden level (baseline) in the PBT2 treated participant
group had an important bearing on the decrease of amyloid over time
in that participant (p=0.035), whereas there was no such
correlation in the placebo group.
Prof Masters further investigated the response of participants
with baseline amyloid burden levels above and below the mean for
the IMAGINE cohort (SUVR of 2.5). He showed that in the subgroup of
PBT2 treated participants with a baseline of SUVR above 2.5, there
was a significant decrease in amyloid burden that was not observed
in participants on placebo nor PBT2 participants with a SUVR less
than 2.5. In summary, whilst the utility of PiB in small trials may
be questioned, it was interesting to note the impact of baseline
SUVR amyloid burden level on the response of a cohort, for future
trial design.
Separately, Prana has confirmed the top line finding that there
is a very promising trend towards the preservation of brain volume
(as measured by MRI) in PBT2 treated patients compared to placebo
patients.
Mechanism of action of PBT2 in AD
PBT2 prevents
formation and toxicity of pathological ABeta species (primarily
soluble oligomers) and promotes their clearance. In Professor
Masters' presentation he proposes the observed effect upon amyloid
burden is due to increased clearance by PBT2 of pools of
PIB-detectable non-fibrillar soluble and membrane bound ABeta.
Through its metal chaperone
activity, PBT2 activates intracellular signalling pathways which
promote neuronal health and plasticity and suppress pathobiological
processes including the abnormal phosphorylation of tau. The trend
towards reduced hippocampal atrophy seen in the PBT2 treatment
group mirrors the Company's preclinical observations and reinforces
a similar trend observed in the Reach2HD Huntington's disease
study.
"Understanding the limitations of a small trial, the atypical
placebo group response, previous clinical findings (the EURO
trial), the strong body of peer reviewed science, along with the
sub-analyses of IMAGINE, the company remains enthusiastic about the
prospects of a large trial statistically powered to demonstrate
cognitive benefit," Prof. Masters said.
IMAGINE EXTENSION TRIAL UPDATE
Patients who
completed the full 12-month term of the IMAGINE trial were eligible
for participation in an open-label Extension study. All
participants in the Extension study receive a 250mg once daily oral
dose of PBT2 for an additional 12 months during which PiB-PET and
MRI imaging will continue.
Thirty three patients elected to join the Extension trial and of
these, 30 remain on the trial. Of those participants, 21 have now
been identified as being randomized to the PBT2 treatment arm in
the IMAGINE study. Of these, all 21 patients have completed 14
months of PBT2 administration, 20 have completed 18 months of PBT2
administration and nine have completed 21 months of PBT2
administration.
We are very pleased with the continuing safety profile of the
drug. The data safety monitoring board has met a further two times
and has not expressed any concerns in relation to adverse
events.
Contacts:
Investor Relations
Rebecca Wilson,
T: +61 3 8866 1216,
E:
rwilson@buchanwe.com.au
Media Relations
Ben
Oliver,
T: +61 3 8866 1233
, E: boliver@buchanwe.com.au
About Prana Biotechnology Limited
Prana
Biotechnology was established to commercialise research into
Alzheimer's disease, Huntington disease and other neurodegenerative
and movement disorders. The Company was incorporated in 1997 and
listed on the Australian Stock Exchange in March 2000 and listed on NASDAQ in September 2002. Researchers at prominent
international institutions including The University of Melbourne, The Mental Health Research
Institute (Melbourne) and
Massachusetts General Hospital, a teaching hospital of Harvard Medical School, contributed to the
discovery of Prana's technology.
Forward Looking Statements
This press
release contains "forward-looking statements" within the meaning of
section 27A of the Securities Act of 1933 and section 21E of the
Securities Exchange Act of 1934. The Company has tried to identify
such forward-looking statements by use of such words as "expects,"
"intends," "hopes," "anticipates," "believes," "could," "may,"
"evidences" and "estimates," and other similar expressions, but
these words are not the exclusive means of identifying such
statements. Such statements include, but are not limited to any
statements relating to the Company's drug development program,
including, but not limited to the initiation, progress and outcomes
of clinical trials of the Company's drug development program,
including, but not limited to, PBT2, and any other statements that
are not historical facts. Such statements involve risks and
uncertainties, including, but not limited to, those risks and
uncertainties relating to the difficulties or delays in financing,
development, testing, regulatory approval, production and marketing
of the Company's drug components, including, but not limited to,
PBT2, the ability of the Company to procure additional future
sources of financing, unexpected adverse side effects or inadequate
therapeutic efficacy of the Company's drug compounds, including,
but not limited to, PBT2, that could slow or prevent products
coming to market, the uncertainty of patent protection for the
Company's intellectual property or trade secrets, including, but
not limited to, the intellectual property relating to PBT2, and
other risks detailed from time to time in the filings the Company
makes with Securities and Exchange Commission including its annual
reports on Form 20-F and its reports on Form 6-K. Such statements
are based on management's current expectations, but actual results
may differ materially due to various factions including those risks
and uncertainties mentioned or referred to in this press release.
Accordingly, you should not rely on those forward-looking
statements as a prediction of actual future results.
SOURCE Prana Biotechnology
