Diabetes 2

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Diabetes 2

  1. 1. Atreyi Banerjee Pipeline products in Phase III
  2. 2. <ul><li>Introduction </li></ul><ul><li>Major mechanism of action </li></ul><ul><li>End points employed in clinical trials </li></ul><ul><li>Duration of trials </li></ul><ul><li>Route of administration </li></ul>Outline
  3. 3. Diabetes <ul><li>Diabetes is a chronic disease that occurs either when the pancreas does not produce enough insulin or when the body cannot effectively use the insulin it produces. Insulin is a hormone that regulates blood sugar. Hyperglycaemia, or raised blood sugar, is a common effect of uncontrolled diabetes and over time leads to serious damage to many of the body's systems, especially the nerves and blood vessels. </li></ul><ul><ul><li>Type 1 Diabetes (previously known as insulin-dependent, juvenile or childhood-onset) is characterized by deficient insulin production and requires daily administration of insulin. </li></ul></ul><ul><ul><li>Type 2 Diabetes (formerly called non-insulin-dependent or adult-onset) results from the body’s ineffective use of insulin. Type 2 diabetes comprises 90% of people with diabetes around the world, and is largely the result of excess body weight and physical inactivity. </li></ul></ul><ul><ul><li>Gestational Diabetes is hyperglycaemia with onset or first recognition during pregnancy. </li></ul></ul>
  4. 4. Epidemiology of Diabetes <ul><li>An estimated 285 million people, corresponding to 6.4% of the world's adult population, will live with diabetes in 2010. The number is expected to grow to 438 million by 2030, corresponding to 7.8% of the adult population. </li></ul><ul><li>The prevalence of diabetes is higher in men than women, but there are more women with diabetes than men. </li></ul><ul><li>While the global prevalence of diabetes is 6.4%, the prevalence varies from 10.2% in the Western Pacific to 3.8% in the African region. However, the African region is expected to experience the highest increase. </li></ul><ul><li>The number of deaths attributable to diabetes in 2010 shows a 5.5% increase over the estimates for the year 2007. This increase is largely due to a 29% increase in the number of deaths due to diabetes in the North America & Caribbean Region, a 12% increase in the South East Asia Region and an 11% increase in the Western Pacific Region. </li></ul><ul><li>Almost 80% of diabetes deaths occur in low- and middle-income countries. </li></ul><ul><li>WHO projects that diabetes deaths will double between 2005 and 2030. </li></ul><ul><li>50% of all diabetics are unaware of their condition. </li></ul><ul><li>The vast majority of people with type 2 diabetes suffer from a range of co-morbidities, such as obesity, hypertension and dyslipidaemia. </li></ul>
  5. 5. Major marketed products in the Type-2 diabetes market <ul><li>Actos (pioglitazone) ‏ Takeda </li></ul><ul><li>Avandia (rosiglitazone) GlaxoSmithKline </li></ul><ul><li>Januvia (sitagliptin) ‏ Merck & Co., Inc. </li></ul><ul><li>Starlix (nateglinide) ‏ Novartis </li></ul><ul><li>Byetta (exenatide) ‏ Amylin Pharmaceuticals, Inc. and Lilly USA, LLC. </li></ul><ul><li>Lantus (insulin glargine) ‏ Sanofi Aventis </li></ul><ul><li>Levemir (insulin detemir) ‏ Novo Nordisk </li></ul>
  6. 6. Primary drugs candidates undergoing phase III clinical trial for Type -2 diabetes <ul><li>BMS-512148 (dapagliflozin) </li></ul><ul><li>Victoza </li></ul><ul><li>D-Tagatose </li></ul><ul><li>JNJ-28431754 (canagliflozin) ‏ </li></ul><ul><li>Albiglutide </li></ul><ul><ul><li>According to New Pharmaceuticals research report from GlobalData 2010 </li></ul></ul>
  7. 7. Five major drugs under phase III clinical trial for Type-2 diabetes
  8. 8. <ul><li>Sodium Glucose Co-transporter (SGLT2 inhibitor) ‏ </li></ul><ul><li>Responsible for at least 90% of the glucose reabsorption in the kidney. </li></ul><ul><li>Subsides as blood glucose concentrations decrease and approach euglycemia </li></ul><ul><li>Oral dosage </li></ul><ul><li>Glycemic control, trend to weight loss </li></ul>BMS- 512148 (dapagliflozin) ‏
  9. 9. <ul><li>Analog of human GLP-1 and acts as a GLP-1 receptor agonist. </li></ul><ul><li>Liraglutide increases intracellular cyclic AMP (cAMP) leading to insulin release in the presence of elevated glucose concentrations. </li></ul><ul><li>Liraglutide also decreases glucagon secretion in a glucose-dependent manner. </li></ul><ul><li>The mechanism of blood glucose lowering also involves a delay in gastric emptying. </li></ul><ul><li>Glycemic control, trend to weight loss </li></ul>Victoza <ul><ul><li>Significant decrease in blood glucose levels as compared to those receiving metformin and rosiglitazone </li></ul></ul>
  10. 10. <ul><li>In the GI tract, tagatose blocks the digestion of sucrose,maltose, and other carbohydrates </li></ul><ul><li>Slows absorption of glucose, and results in little or no spike in glucose after meals. </li></ul><ul><li>In the liver, Tagatose competitively blocks the enzyme that metabolizes glucose to be referentially stored as glycogen. </li></ul><ul><li>Oral dosage </li></ul><ul><li>Glycemic control determined by a statistically significant decrease in hemoglobin </li></ul>D-Tagatose
  11. 11. JNJ-28431754 (canagliflozin) ‏ <ul><li>Sodium Glucose Co-transporter (SGLT2 inhibitor) ‏ </li></ul><ul><li>Oral dosage </li></ul><ul><li>glycemic control,stable blood pressure, weight loss </li></ul><ul><li>But has some effect on renal function </li></ul>
  12. 12. <ul><li>GLP-1 (Glucagon-like peptide 1) agonist </li></ul><ul><li>DPPIV resistance and fusion to human albumin </li></ul><ul><li>Once-weekly or less frequent; subcutaneous injection using pen with small gauge needle </li></ul><ul><li>Demonstrated effective glycemic control, trend to weight loss, low incidence of GI side effects and low immunogenicity </li></ul>Albiglutide <ul><ul><li>Albiglutide is the only medication which fuses human GLP-1 to human albumin.  It is designed to have an extended duration of action and allow for weekly or less-frequent injections. </li></ul></ul>
  13. 13. Major mechanism of action under development <ul><li>SGLT-2 inhibitors </li></ul><ul><li>Interleukin-1¦Â antagonists </li></ul><ul><li>CCR2 antagonists </li></ul><ul><li>GLP-1 agonists </li></ul><ul><li>DPP-IV Inhibitors </li></ul><ul><li>11¦Â HSD inhibitors </li></ul><ul><li>Immune modulators </li></ul><ul><li>Antisense drugs targeting glucagon receptor </li></ul>
  14. 14. End points employed in clinical trials <ul><li>Survival </li></ul><ul><li>Completes response </li></ul><ul><li>Objective Response Rate </li></ul><ul><li>Progression Free Survival </li></ul><ul><li>Clinical benefit </li></ul><ul><li>Endpoints for selected drugs were HbA1c change from baseline and safety and tolerability with minimised or no adverse effects. </li></ul><ul><li>The secondary endpoints were change from baseline mean morning fasting body weight and renal glucose threshold maintenance. </li></ul>
  15. 15. X X The average duration of study is 2 years and 6 months as calculated from www.clinicaltrials.gov Disease Progression Duration of trials Survival (X) ‏ X X X Censored
  16. 16. Route of administration <ul><li>Oral </li></ul><ul><ul><li>Digestive tract (enteral)‏ </li></ul></ul><ul><ul><li>Sublingual/ Sublabial </li></ul></ul><ul><ul><li>Respiratory tract </li></ul></ul><ul><li>Parenteral </li></ul><ul><ul><li>Subcutaneous Injection </li></ul></ul><ul><ul><li>e.g. Byetta (exenatide)‏ </li></ul></ul><ul><li>Surgical </li></ul><ul><ul><li>Islet cell transplant predominantly Allogenic. The shortage of human donor pancreases for islet cell transplantation has led to a search for alternative sources of islet cells. Autologous is used to treat Type-1 patients when diabetes is not already present. </li></ul></ul>
  17. 17. WHO activities to prevent and control Diabetes <ul><li>WHO aims to stimulate and support the adoption of effective measures for the surveillance, prevention and control of diabetes and its complications, particularly in low and middle-income countries. To this end, WHO: </li></ul><ul><ul><li>provides scientific guidelines for diabetes prevention; </li></ul></ul><ul><ul><li>develops norms and standards for diabetes care; </li></ul></ul><ul><ul><li>builds awareness on the global epidemic of diabetes; including partnership with the International Diabetes Federation in the celebration of World Diabetes Day (14 November); </li></ul></ul><ul><ul><li>conducts surveillance of diabetes and its risk factors. </li></ul></ul><ul><li>The WHO Global Strategy on Diet, Physical Activity and Health complements WHO's diabetes work by focusing on population-wide approaches to promote healthy diet and regular physical activity, thereby reducing the growing global problem of overweight and obesity. </li></ul>
  18. 18. Overall categorization of diabetes treatments
  19. 19. The key market players at present are Hoffmann-La Roche, Novo Nordisk, Merck & Co., Novartis Ag, Sanofi-aventis, Eli Lilly & Company and GlaxoSmithKline reinstated by the figure above. Competitive dynamics of the leading players in the global diabetes market, 2005
  20. 20. Global* market share of leading insulins (%), 1999-2003 , The leading giant still is the US with more than 50% market share while the Pacific region is still growing owing to the large population of Diabetic patients in Japan and South Asia.
  21. 21. Conclusion <ul><li>The U.S. diabetes market has grown to more than $5 billion as the disease becomes more prevalent. Thus a rise in competitors. </li></ul><ul><li>Seven out of ten marketed diabetic drugs are oral proving that patients prefer oral administration of medicines. </li></ul><ul><li>The presently developed drugs have good toxicity profile which is very essential in today's market. </li></ul>
  22. 22. References <ul><li>www.clinicaltrials.gov </li></ul><ul><li>www.worlddiabetesfoundation.org </li></ul><ul><li>www.who.int/en/ </li></ul><ul><li>www.gsk.com </li></ul><ul><li>www.globaldata.com/reportstore/ </li></ul><ul><li>www.uchospitals.edu </li></ul><ul><li>www.msnbc.msn.com </li></ul>

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