The Hoodia Cactus
P57 in human testing
Proof of Principle Clinical Study of P57 for
Obesity - Successful Completion of Second Stage (Phase 2)
http://www.phytopharm.co.uk/index.htm
05 July 2003
Phytopharm plc (PYM: London Stock Exchange) (Phytopharm) announces today the
successful completion of the second stage of its clinical study of P57 for
obesity. The objectives of this stage of the study include evaluation of the
safety, tolerability and pharmacokinetic profile of P57, a patented oral product
licensed to Pfizer Inc., which is under development as an appetite suppressant for the treatment of obesity.
The third and final stage of the study has been designed to assess the safety,
tolerability, pharmacokinetics and effects on daily calorie intake of P57
compared to placebo when administered repeatedly over at least 10 days to
healthy, overweight volunteers. .
Obesity is a global problem, which affects more than 100 million people
seriously enough to warrant medical intervention. It is a direct causal
contributor to the pathophysiology of many diseases and exacerbates numerous
others. Among these are five of the leading causes of death in the
industrialized world: stroke, atherosclerosis, cardiovascular disease, diabetes
and cancer. According to the World Heath
Organization (WHO), obesity accounts for tens of billions of pounds in direct
healthcare costs worldwide. A panel of experts convened by WHO stated on 12 June
1997 that 'obesity's impact is so diverse and extreme that it should now be
regarded as one of the greatest neglected public health problems of our time. It
has an impact on health, which may well prove to be as great as that of smoking'
(World Health Organization, 1997)
Dr Richard Dixey, Chief Executive of Phytopharm, said:
'We are very encouraged by the results of the second stage of the study and
await the completion in early November of the third and final stage of this
proof of principle study'
P57 - Background to Anti-Obesity Drugs
Obesity
Obesity is a global problem which affects more than 100 million people seriously
enough to warrant medical intervention. It is a direct causal contributor to the
pathophysiology of multiple diseases and disorders and exacerbates numerous
others. Among these are five of the leading causes of death in the
industrialized work: stroke, atherosclerosis, cardiovascular disease, diabetes
and cancer. According to the World Heath Organization, obesity accounts for tens
of billions of pounds in direct healthcare costs world-wide. A panel of experts
convened by WHO stated on 12 June 1997 that 'obesity's impact is so diverse and
extreme that it should now be regarded as one of the greatest neglected public
health problems of our time with an impact on health which may well prove to be
as great as that of smoking'.
Etiology
Very little is known about the precise disease mechanism in obesity. Excessive
dietary intake of fats contributes to obesity but at the same time an imbalance
between energy input and energy output is also a cause. It is believed there is
a hereditary component and socio-economic factors are known to play a role,
particularly in developed countries. Management of obesity can include medical
intervention, exercise and diet routines, but the compliance and success rate is
typically poor.
The Market
http://www.phytopharm.co.uk/metabframe.htm
Prevalence of Obesity (BMI > 30) in a
representative sample between 16-64 years
16-24 25-34 35-49 50-64
Europe 6% 2.1m 10% 5.8m 16% 12.2 m 21% 11.3m
USA 9% 2.7m 18% 7.1m 29% 15m 36% 14m
Total 4.8m 12.9m 27.2m 25.3m
*Adapted from data of White et al 1991, UK Office of Population Consensures and
statistics (OPCS) and US National Institute of Health, Office of Health
Economics 1994.
Pharmaceutical Market
Prior to the decision to remove dexfenfluramine and fenfluramine from the world
market in September 1997, the prescription market was estimated at approximately
US$ 400 million in the United States alone. The underlying medical need for an
effective anti-obesity pharmaceutical can be estimated by the dramatic increase
in sales of fenfluramine from US$ 600,000 in 1991 to $188 million in 1996
following its approval as a treatment for obesity by the FDA.
The growth potential for an effective pharmaceutical is very high as the obese
populations in Europe and the US continue to increase. The current low growth
rates and relative market sizes reflects the lack of safe and effective
treatments for a condition which is not fully understood.
Few drugs are specifically approved for obesity and those that are suffer from
limited efficacy and/or side effects. Most patients become tolerant to these
drugs and weight loss greater than 5 -10% is rarely achieved.
P57: A Naturally Occurring Appetite Suppressant
http://www.phytopharm.co.uk/metabframe.htm
P57 is a plant based product for the
treatment of obesity which is now in clinical development. The product was
licensed to Pfizer Inc in 1998 in a global licensing agreement
The cactus from which P57 was
derived.
The Hoodia Cactus
P57 is a fully characterized extract derived from a single plant which is
subject to patent applications covering raw materials, active substances and
mode of action. It appears to have novel pharmacological properties and may in
fact be the first ever true appetite suppressant to be discovered. Unlike many
of the conventional treatments currently available it has no effects on
behavior. The mechanism of action is novel and distinct from those of recently
available compounds. Efficacy has been established with a profound weight loss and a good emergent safety profile.
Considerable progress has been achieved
with this project. Phase I clinical development continues alongside an extensive
research program. In parallel to these activities, additional plantations for
the plant material have been established world-wide in collaboration with the
CSIR and Pfizer and a clinical supplies unit, dedicated to the manufacture of
the material, has been opened in South Africa.
Pharmacology
Anecdotal reports of the use of P57 in humans show that it significantly reduces
appetite, food intake and body weight. Considerable work has been undertaken to
fractionate this plant material and a number of compounds have been isolated
from the mixture, some of which have biological activity. The mechanism of
action of P57 and its active constituents is currently under investigation.
Additional pharmacological properties have recently been established.
Clinical
To date 24 obese (BMI>26) and 42 non-obese non-patient volunteers have received
doses of P57P ranging from 3 to 4000 mg. Primary measures in these studies
included clinical toleration, hematological and biochemical assessments of
safety and pharmacokinetics. No treatment related serious adverse events have
been reported.
Intellectual Property
Through an extensive program of research a molecule has been identified which
appears to be responsible for part if not all of the desired therapeutic
activity. This molecule and synthetic derivatives are subjects for patent
activity.
Development Status
A program designed to achieve registration of a product as a prescription
medicine for human use in Europe and USA has been initiated.