Claus Kühl, Health Care Discovery
Diabetes is a serious, chronic disease and people with diabetes can expect to suffer from the symptoms throughout their lives. In the U.S.A., for example, diabetes is the third leading cause of death from disease - far exceeding that of many well-known cancers.
The current estimate is that more than 100 million people suffer from diabetes. This equals 2% of the world's population. The figure is even expected to double within 15 years.
Slide 3 - Facts on Diabetes - Expected growth in Type 1 and Type 2 diabetes 1994-2010
This slide shows the distribution of Type 1 and Type 2 diabetes in a number of main geographical regions and the expected growth of Type 1 and Type 2 diabetes in these markets.
As can be seen, Type 2 is by far the most common type of diabetes, and the ratio between Type 2 and Type 1 is expected to increase as standards of living in the developing countries approach those of the Western countries. Furthermore, Asia will increasingly, from a commercial point of view, become a leading potential diabetes market, increasing its proportion to around 60% of the total number of diabetics in the world within the next 15 years.
Slide 4 - Facts on Diabetes - Prevalence and current treatment
Current data from several sources in the U.S.A. estimate a total of 16 million people with diabetes in the U.S.A. alone. The estimates for 1995 have been extrapolated from regional registers as no national register exists.
It must be emphasised that half of these 16 million people are not diagnosed, and that almost all of the undiagnosed patients are supposed to have Type 2 diabetes, since the severity of symptoms most often lead to immediate recognition of Type 1 diabetes. It can reasonably be assumed, that the percentage of undiagnosed patients in, for example, Asia is at least of the same magnitude and probably even considerably larger. In rural India figures show approximately 70% undiagnosed patients (reference: IDF 1994).
The treatment of Type 2 diabetic patients begins with diet and exercise. As the disease progresses, treatment is extended with Oral Hypoclycaemic Agents (OHAs). 20% of the patients will later continue on to insulin.
The current trend within Type 2 treatment is that the percentage of patients where diet alone is sufficient to control the disease, is stable or slightly decreasing. Treatment with OHA is decreasing in most markets, except for Germany and the U.S.A. while the use of insulin or a combination of OHA and insulin is increasing in all markets.
Slide 5 - Facts on Diabetes - Distribution of costs
In the U.S.A. the annual cost of diabetes and its complications is more than USD 92 billion split equally between direct and indirect costs, driving up the overall health care costs more than any other single disease.
The drug costs of insulin and OHA represent only a very small proportion of the overall costs of diabetes. Again, in the U.S.A. this amounts to around 2% of the total costs of diabetes care. Even adding the costs of monitoring blood glucose levels brings the figure up to no more than 3%.
It is mainly the costs of treating the consequences of late complications to diabetes that are responsible for the huge economic burden on society. The only realistic option open to significantily contain the costs of treating diabetes is therefore to invest in the prevention of the development of late complications, and this is therefore also a main focus area of our discovery strategy within diabetes.
Slide 6 - Diabetic late complications - Prevalence and costs
Both Type 1 and Type 2 diabetes are associated with a high frequency of disabling and costly complications that occur late in the disease process.
Some of these, i.e. diabetic retinopathy and diabetic kidney disease, are particular to diabetes while others, i.e. cardiovascular complications are also related to other diseases. Especially in patients with Type 2 diabetes, cardiovascular complications are much more frequent than seen in the general population.
The costs of treating patients with diabetic late complications are dominated by the high expenses for treatment of kidney disease, i.e. haemodialysis and kidney transplantation. Rating second is the treatment of cardiovascular diseases, including treatment of hypertension, hyperlipidaemia, coronary by-pass surgery and amputations due to peripheral vascular diseases.
Among diabetes health care providers it is generally acknowledged that intensified insulin treatment and blood glucose monitoring can substantially reduce the frequency and severity and hence also the cost of these complications.
Slide 7 - Diabetic late complications - Prevention is key
A number of large, prospective studies including the U.S. DCCT (Diabetic Complications and Control Trial) have proven that good glycaemic control can reduce the frequency of serious diabetic late complications by around 50%.
It is Novo Nordisk's intention to continue to champion the concept of good glycaemic control in order to contain costs of treatment of diabetes and improve quality of life for these patients.
This will be achieved by offering a comprehensive package comprising key elements such as intensive insulin treatment regimens, home blood glucose monitoring and early intervention with insulin treatment in people with Type 2 diabetes.
It should be noted that Novo Nordisk already in 1985 started to promote the importance of tight glycaemic control and furthermore made it much more convenient for the patients to achieve this goal by the introduction of NovoPen®, the world's first truly convenient insulin injection device.
These concepts will be supported by education and training materials for physicians, nurses and patients, treatment guidelines and systematic collection of outcomes data to document the clinical and health economic effects of the implementation of these concepts.
Slide 8 - Novo Nordisk's focus within diabetes discovery
Novo Nordisk has been a major player in the treatment of people with diabetes since 1923, when we first began to produce insulin. Ever since we have been at the forefront of developing new and better insulin preparations and we have also, as previously mentioned, developed state-of-the-art insulin injection devices such as NovoPen® and NovoLet® (for the U.S.A.: Novolin Prefilled). For many years the main focus of our diabetes discovery was insulin chemistry.
However, during recent years, Novo Nordisk's diabetes discovery has broadened its scope quite significantly to now also encompass the areas of intervention and prevention of Type 1 diabetes, Type 2 diabetes, obesity and diabetic late complications. In particular, Type 2 diabetes has become a major area of discovery research; the number of patients is rapidly increasing and the need for more efficient therapy than what is available today is evident.
In the Type 1 diabetes area, we have major discovery programs within intervention and prevention, including a collaborative project with Anergen, Inc., of the U.S.A., which aims at stopping the autoimmune process which destructs the pancreatic beta-cells.
In the Type 2 field, we have launched several projects dealing with obesity, a condition that often either precedes or coincides with Type 2 diabetes. Furthermore, we are looking at programs that potentiate the insulin action on the cells. Also, projects aiming at a lowering of blood glucose due to inhibition of glucose production by the liver continue to be an important part of our discovery portfolio. Our long-acting insulin analogue has shown very promising preclinical results that were reported at the European Association for the Study of Diabetes meeting in Stockholm in September of last year. You will see some preliminary results on the next slide.
Finally, we are looking at orally active small molecule compounds which act like insulin and are therefore called "insulin mimetics". These would, undoubtedly, be highly appreciated by both Type 1 and Type 2 diabetic patients because they would render insulin injections superfluous. However, it is still early days in this respect.
As earlier mentioned, it is well known that poor diabetes control involves a high risk of leading to the development of late complications. Whereas there are more and more patients today, who by applying our state-of-the-art insulin products and insulin injection devices together with home monitoring of glucose, are capable of achieving and maintaining a very good control, it is, however, obvious that not all patients achieve good control. We will therefore, unfortunately, also in the future continue to see a high number of patients who develop late complications to diabetes. This is why we also have a discovery program aiming at the development of drugs for both the prevention and the treatment of late complications.
Slide 9 - Novo Nordisk's long acting insulin analogue
The slide shows that our long-acting insulin analogue has a longer half-life and a smoother action profile than NPH insulin which is today's most used long-acting insulin. The long-acting insulin analogue will enter into human trials this year.
Slide 10 - Current Diabetes Topics
Novo Nordisk is currently finishing the clinical development of a new and unique OHA called NovoNormTM. NovoNormTM has a short duration of action and it has proven to give rise to fewer cases of hypoglycaemia as compared to other OHAs even in patients who skip a meal.
Like Eli Lilly, Novo Nordisk is also developing a short-acting insulin analogue. These analogues can be injected at the beginning of a meal instead of 30 minutes before which is recommended for conventional short-acting insulins. Overall glycaemic control does not seem, however, to be better on the short-acting insulin analogue, so it is still debated whether they cover a true patient need. In contrast, the need for a long-acting analogue is much greater.
Transplantation of beta-cells has been tried in a limited number of patients on a strictly research basis and often in connection with kidney transplants. In some instances, a significant lowering of blood glucose have been achieved, but long-time survival of the beta cells, the requirement for a very high number of cells and the need for continuous immunosuppressive therapy remain unresolved problems. Likewise, pancreas transplantation will always remain a therapy for only a very low number of patients. The development of gene therapy for diabetes is complicated by the fact that neither Type 1 nor Type 2 diabetes are caused by single gene defects. This is why we believe that gene therapy is far away and it may not even ever happen.
Frequent control of blood glucose is a pre-requisite for good diabetes therapy. Today's procedures are all invasive, in that finger or earlobe pricking is required to obtain the blood sample. Non-invasive devices are currently being developed, but there are still significant technical hurdles that need to be overcome.
Slide 11 - Novo Nordisk - New technologies in diabetes discovery
Diabetes discovery has been strengthened considerably during recent years by the appliance of new technologies such as molecular biology and computational biology. These are focus areas for our diabetes discovery units in Denmark and the U.S.A. We continue to improve our skills in molecular modelling and combinatorial chemistry and to improve the sensitivity and capacity of our screening techniques.
