Press Release

ALIZYME ANNOUNCES PRELIMINARY RESULTS FROM ITS SUCCESSFUL PHASE IIb CLINICAL TRIAL OF CETILISTAT IN OBESE DIABETICS

Results confirm cetilistat’s competitive profile and qualification for
Phase III clinical development

Cambridge UK, 12 December 2005: Alizyme plc (LSE:AZM) is pleased to announce the preliminary results of its successful Phase IIb clinical trial of cetilistat in clinically obese diabetic patients.

Highlights of the results:

• Primary endpoint met with statistically significant weight loss with cetilistat

• Statistically significant reduction in diabetes marker HbA1c

• No difference between the cetilistat groups and placebo group in treatment discontinuations due to gastro-intestinal adverse events, nor in the level of severe gastro-intestinal adverse events

• Treatment discontinuations were notably higher in the Xenical® group, which showed similar weight loss and reduction in HbA1c to that for cetilistat

• Adverse events, gastro-intestinal adverse events and severity of such events were notably lower in the cetilistat groups than in the Xenical® group

• Cetilistat treatment was safe and generally well tolerated

This multi-centre clinical trial for cetilistat enrolled 612 clinically obese patients and was performed in 37 centres in 5 European countries, including the UK. It was a randomised, double-blind, parallel group design, dose-ranging study comparing three doses of cetilistat (40mg, 80mg and 120mg) with placebo and with Xenical® (120mg), all taken three times daily. The objectives of the study were to determine the effect of cetilistat on weight loss and on markers of diabetes, together with its safety and tolerability profile, in clinically obese diabetic patients having a Body Mass Index (BMI, see Editor’s Notes) between 28 and 45, with their diabetes managed with the anti-diabetic drug, metformin.

The trial met its primary endpoint of statistically significant weight loss (3.85kg and 4.32kg loss at 80mg (p=0.01) and 120mg (p=0.0002)) compared with placebo (2.86kg). Xenical® caused comparable weight loss (3.78kg, p=0.008). These levels of weight loss (Intent To Treat (ITT) population with Last Observation Carried Forward; LOCF) measured over the twelve week treatment period, were consistent with that of other approved obesity drugs.

Cetilistat, at the two active doses (80mg and 120mg), also caused statistically significant (p<0.02) reductions in HbA1c (see Editor’s Notes), a marker of diabetic control, of between 0.5% and 0.6%, from a baseline of approximately 7.2%. Similar results were obtained with Xenical® (p<0.05). This level of reduction is similar to that reported in clinical trials with other obesity drugs. Consistent with a patient population with baseline values for total cholesterol, LDL-cholesterol or HDL-cholesterol within the normal range, there were no significant changes observed in these parameters in any treatment group.

The proportion of subjects discontinuing treatment during the trial was lower in the cetilistat groups (15.7%, 14.0% and 11.7% for the 40mg, 80mg and 120mg doses respectively) than that in the placebo (17.5%) and Xenical® (18.5%) groups. Furthermore, the proportion of subjects discontinuing for reasons of adverse events were 2.5%, 5.0% and 2.5% for the cetilistat treated groups respectively and 6.4% for the placebo group with the Xenical® group being substantially higher at 11.6%. Subjects discontinuing treatment due to gastro-intestinal adverse events were fewer at 0.8%, 2.5%, 1.7% for the cetilistat treated groups and 4.0% for placebo group whereas all the discontinuations in the Xenical® group at 11.6%, were attributable to gastro-intestinal adverse events.

The total number of gastro-intestinal adverse events reported in the placebo group were 153 and cetilistat treatment groups were 294, 282 and 339 respectively, with a substantially higher number of 431 being reported in the Xenical® treated group. In addition, the number of gastro-intestinal adverse events classified as moderate or severe was substantially higher in the Xenical® group at 179, than in the cetilistat groups at 97, 104, 125 respectively or placebo at 53.  Overall, cetilistat was safe and generally well tolerated.

Professor Peter Kopelman, Principal Investigator commented:

“This trial has confirmed the potential utility of cetilistat for the management of obese diabetic patients. The substantial reduction in the number and severity of the adverse events experienced by patients taking cetilistat is very encouraging. A crucial element for the successful management of obesity is the patient’s adherence to their prescribed medication�.

Dr. Richard Palmer, Chief Executive Officer commented:

“We are delighted with these results, which demonstrate a level of efficacy for cetilistat consistent with that achievable by other weight loss drugs. In addition, the improvement in HbA1c, a key marker of diabetic control, supports the potential utility of additional drug treatment in the management of obese diabetic patients. The generally inconsequential adverse event profile in this patient population, which is consistent with  the differentiated product profile shown in our previous Phase Ib trials and our previous Phase IIb trial in obese subjects, supports the attractiveness and competitiveness of cetilistat’s product profile. These results confirm the commercial potential of cetilistat, and allow us to prepare for Phase III development, whilst continuing dialogue with potential licensing partners.

“These excellent results now mean Alizyme has its third proprietary product in, or appropriate for, Phase III clinical development.�

For further information, please contact:

Dr Richard Palmer, Chief Executive Officer
Mr Tim McCarthy, Finance Director
ALIZYME plc 

Tel No: + 44 (0) 1223 896000

Lisa Baderoon/Rebecca Skye Dietrich
BUCHANAN COMMUNICATIONS 
Tel No: + 44 (0) 20 7466 5000

Further information on Alizyme can be found on the Company’s website: www.alizyme.com
 
EDITOR’S NOTES

Alizyme plc
Alizyme is a speciality biopharmaceutical development company, based in Cambridge, UK, targeting the treatment and management of gastrointestinal disorders, obesity and diabetes. It has a portfolio of products which, in addition to cetilistat, includes renzapride (Phase III for the treatment of constipation-predominant irritable bowel syndrome in the US), COLAL-PRED® (Phase III for the treatment of acute ulcerative colitis in Europe), and ATL-104 (completed recruitment into a Phase IIa trial for mucositis).

Cetilistat
Cetilistat, an inhibitor of gastrointestinal lipases, is designed to cause weight loss by reducing the digestion and thus the absorption of fat from the diet.

In August 2003, Alizyme’s wholly owned subsidiary, Alizyme Therapeutics Limited, granted Takeda Chemical Industries, Ltd. rights to an exclusive licence to develop, manufacture and market cetilistat in Japan for the treatment of obesity coupled with its associated conditions, such as Type II diabetes. Alizyme currently retains all rights to cetilistat in the rest of the world, and will now continue discussions with interested parties for a licence to the global rights (excluding Japan), whilst continuing to complete activities in preparation for Phase III clinical development.

Obesity Incidence
The incidence of obesity has shown a substantial increase over the past twenty years. The World Health Organisation (WHO) has identified obesity as an epidemic and as the largest global, chronic health problem in adults. In 2003, the WHO estimated that worldwide, over 300 million adults are estimated to be clinically obese (Body Mass Index over 30 or over 28 with co-morbidities - see below for definitions), while 1 billion are overweight. Figures for the UK show the problem is increasing with 13.2% and 17.0% of men and 16.4% and 19.7% of women, in 1993 and 1997 respectively, being classified as clinically obese. Although the disease is becoming high profile, as it is increasingly being recognised as a significant factor in the development of serious medical complications, the market currently represents a substantial unmet medical need.

Health Implications
Obesity is a poorly understood disease. It is considered to be a complex syndrome involving many different physiological processes. What is clear is that health risks increase as the degree of obesity increases. In particular, there is an increased risk of Type II diabetes, cardiovascular and joint diseases. These health risks are substantially reduced with loss of weight. Obesity and these associated conditions are chronic and therefore, have major consequences for healthcare spending. Conservative estimates of the economic costs of obesity range from 2% to 8% of the total costs of healthcare of the developed world. The National Institutes of Health (NIH) indicate that healthcare costs attributable to obesity in the US are approximately $100 billion annually.

Drug Treatment of Obesity
Drug treatment is being recommended for individuals with a Body Mass Index of over 30 (see definition below). In the past, treatments have included appetite suppressants or bulking agents. Meridia®/Reductil® (sibutramine), an appetite suppressant that acts on the central nervous system (centrally acting), was launched by Knoll/BASF (now Abbott) in the USA in 1998, is now approved in Europe and was launched in the UK during 2001.

Roche’s Xenical® (orlistat), inhibits lipases (fat splitting enzymes in the digestive tract) to reduce fat absorption. This leads to fewer calories being absorbed, thus resulting in weight loss. Xenical® was first approved in 1997 and is now marketed in more than 100 countries with current sales of approximately $450 million per annum.

Cetilistat, an inhibitor of lipases, is designed to cause weight loss by blocking the digestion and thus the absorption of fat from the diet. Cetilistat acts in a similar way to Xenical®. Weight loss with Xenical® significantly improves various risk factors for cardiovascular and metabolic disease, including elevated cholesterol and insulin levels. Xenical® has also shown benefit for the treatment of Type II diabetes in obese patients and is also approved for adolescents.

HbA1c
The red blood cells contain high levels of a chemical called haemoglobin, which transports oxygen around the body. Glucose can attach to the haemoglobin to form a ‘glycosylated haemoglobin’ called HbA1c. The more glucose in the blood, the more HbA1c will be present. Measuring HbA1c is a way of checking that blood sugar level and thus diabetes, is under control. The normal range is below 6.0%.

Body Mass Index: Definition

The classification of overweight and obesity is based on the Body Mass Index (BMI) measurement, calculated as:

BMI = Weight (kg)
  Height (m)2

Body Mass Index Ratios (BMI) and classification of obesity

BMI Medical Classification
> 30 Clinical obesity leading to a dramatic rise in likelihood of suffering Type II diabetes, high blood pressure, heart disease, osteoarthritis etc
 Mortality increases significantly.
> 28 Clinical obesity when other certain medical conditions are present
25-29.9 Overweight. There is a significant increase in obesity related diseases.
20-25 Most appropriate for long term health.

 

 

The identification of compounds for successful research, their progress through development and the obtaining of regulatory approvals or authorisations before marketing, manufacture and/or distribution of products is not certain or a formality.

 

 

Last updated on: 27/08/2010 11:40:18