ASX Announcement 31 January 2006
adds
value to Metabolic’s obesity drug
• Animal study showing orally delivered obesity drug AOD9604 has potential
as a treatment for osteoporosis
• The world market for osteoporosis drugs in 2004 was US$6 billion,
projected to grow significantly as the population ages
• Study confirms efficacy of oral delivery of AOD9604 in another model
Metabolic has received data from collaborators demonstrating that daily oral administration of
AOD9604 shows an effect in preventing bone loss and maintaining bone quality in a rat model of
osteoporosis. This potential new indication for AOD9604 is in addition to its use for obesity,
currently under investigation in the clinic.
The osteoporosis study which includes approximately 90 rats, was conducted by a team of
scientists under the direction of Dr Marc Grynpas at the Samuel Lunenfeld Research Institute of
Mount Sinai Hospital (New York) affiliated with the University of Toronto.
This result confirms a
previous study performed at the same site in 2002 with injected AOD9604 at slightly higher doses.
Dr Roland Scollay, CEO of Metabolic, said “a new indication for an existing investigational drug is
always positive news.
AOD9604 already has the potential to be a multi-billion dollar drug through
its effects on obesity. An additional indication would increase the potential market size, and
therefore royalty flow, while much of the knowledge gained for the primary indication, such as
safety profiles, manufacturing, formulation and drug stability could be used to support the new
indication.”
The Company has been investigating the biology of AOD9604 in a variety of models, and
commissioned this study using a well accepted animal model of osteoporosis. In this model, post
menopausal estrogen loss was simulated in retired female breeder rats by surgical removal of the
ovaries, which results in substantial fat gain and loss of bone quality and strength over the study
period.
Once daily oral treatment with AOD9604 (10-15 animals per group) for 12 weeks at both
doses used, 0.25 mg/kg/day and 0.5 mg/kg/day, reduced the post ovariectomy weight gain by
approximately 50% compared to untreated controls (statistically highly significant at p<0.001), but
also prevented the loss of bone mass and bone strength in cortical bone (one of the two major
bone types) seen in the untreated controls (statistically significant at p<0.05). This indicates that
AOD9604 could be useful in the prevention of osteoporosis, in a similar way to estrogen,
bisphosphonates or other preventive treatments.
This study has also provided third party confirmation of the efficacy of AOD9604 in the treatment of
obesity, the primary indication, after once daily oral delivery in a new model.
While these animal studies will need confirmation in a human context, they indicate that AOD9604
may have a beneficial role in another major area of health concern. Planning is now under way for
additional animal studies to learn more about the effects of AOD9604 on bone.
Background
As humans age, the levels of several hormones gradually decline, including estrogen, testosterone
and growth hormone, creating imbalances in a variety of metabolic functions, including fat and
bone metabolism.
The age related decline in growth hormone levels is a substantial contributor to
weight gain in older people and, in addition to estrogen (in women) and testosterone (in men), is
known to have a role in the loss of bone quality usually seen in old age.
AOD9604 is a 16-amino acid, orally active peptide modelled on one segment of the growth
hormone molecule, effective with once daily oral dosing. It has been shown in several studies to
have similar effects on fat metabolism as the intact growth hormone, but none of the unwanted
effects of the hormone on body growth which limit the use of the whole hormone as a therapeutic.
The rationale for the use of AOD9604 as a treatment for obesity, currently under investigation in a
Phase 2B trial, is to avoid the side effects, but to restore the fat metabolic actions of growth
hormone, since the production of hormone by the body is suppressed both by age and by obesity
itself. The study reported here suggests that the same rationale may apply to AOD9604 as a
treatment for osteoporosis.
The osteoporosis study outlined in this announcement, and the related previous study was
performed at an independent academic institution, but both were funded by Metabolic and used
drug material provided by the Company.
The Osteoporosis Market
In the US, there are about 30 million individuals over the age of 50 with osteoporosis and the
number is increasing as the population ages. In Australia, 1.9 million people had osteoporosis in
2002 and the number is expected to be three million by 2021.
According to Osteoporosis Australia,
one in two women and one in three men over the age of 60 will have a fracture due to
osteoporosis. Up to 20% of aged osteoporosis patients die from the complications of hip fracture
and 40% can no longer live independently. The World Health Organisation estimates that the total
treatment costs associated with osteoporosis are US$18 billion worldwide.
Worldwide sales of the top seven osteoporosis drugs in 2004 were over US$6 billion, with
Fosamax from Merck and Co (a bisphosponate) the number 12 drug in the world at just over US$3
billion. A recent addition, Forteo from Eli Lilly, is an injectable fragment of parathyroid hormone. It
had sales of US$238 million in 2004, a four-fold increase on 2003.
Current Phase 2B clinical trial for AOD9604 primary indication – Obesity
The Company’s key focus remains the progression of its low dose Phase 2B human clinical trial of
AOD9604, for its primary indication, obesity.
The current trial which commenced in October 2005
is proceeding on schedule, as advised in the ASX Announcement of 23 January 2006 which
provided the latest update on the trial (available via www.metabolic.com.au). The trial has been
designed to evaluate the drug’s efficacy following daily oral delivery of lower doses of AOD9604
than previously tested.
- ENDS -
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