BELVIQ POWERPOINT UPDATE SUMMER 2013

1. BELVIQ POWERPOINT UPDATE SUMMER 2013 Steven Vig md

2. BELVIQ, a new centrally acting pill for weight loss 2013 Steven Vig M.D.

3. Obesity is a huge problem • 2/3 of Americans are overweight. • 1/3 of Americans are obese. • Type two diabetes is on the rise. • Pediatric obesity is increasing. • Mexico has the highest rate of obesity. • The United States has the second highest rate of obesity.

4. Welcome to America !

5. The Beltline of Americais increasing.

6. Obesity in America in 2012

7. Too much fast food.

8. Too many sweets.

9. Too many desserts.

10. Too many high calorie beverages.

11. What is the result ?

12. A boatload of trouble !

13. A truckload of trouble !(double trouble)

14. A syringe full of trouble ! (diabetes)

15. A chest full of trouble ! (heart disease)

16. A brain full of trouble ! (stroke)

17. Joints full of trouble(osteoarthritis)

18. Trouble for the pediatricians. • “Supersize it !”

19. Trouble for the sleep apnea doctors.

20. Trouble for the whole world.

21. Higher rates of cancer due to obesity.

22. Even the vets are seeing it.

23. How do we get to the bottom of this problem ?

24. How do we get unstuck from this problem ?

25. Legislation ?

26. Consumer education ?

27. BELVIQ (lorcaserin) • Take one 10 mg tablet twice a day with or without food for weight loss.

28. Chemical Structure • BELVIQ (lorcaserin)

29. Belviq • 5HT2c serotonin receptor agonist. • Works in hypothalamus to decrease appetite. • Belviq was FDA approved on 6 /27 /2012. • For obese patients with BMI at or above 30. • For overweight patients with BMI 27 to 30 who have at least one condition related to excess weight, such as type two diabetes, high lipids, or high blood pressure.

30. Arena Pharmaceuticals • A Biotechnology company in San Diego, California. • Publicly traded on the Nasdaq. • Ticker symbol is ARNA. • The CEO is Jack Lief. • Web site is WWW. ARENAPHARM. COM • Belviq arrived in pharmacies in the USA on 6/11/2013.

31. Partnership with Eisai • Arena Pharmaceuticals has partnered with the large Japanese pharmaceutical company Eisai for sales of Belviq in the United States, Canada, Brazil, Mexico, and other western hemisphere countries. • Arena will get 31.5 to 36.5 % of net sales of Belviq in the United States, plus milestone payments. • Belviq is made in Arena’s manufacturing facility in Switzerland.

32. Don’t forget…. • Belviq is indicated for weight loss ALONG WITH DIET AND EXERCISE .

33. Eat healthy food !

34. Exercise !

35. Patents and partnerships • Belviq patents will continue until at least 2023 in most jurisdictions, plus extensions. • Arena has partnered with Eisai for sales of Belviq in most of the western hemisphere. • Arena has partnered with Ildong Pharmaceutical for sales of Belviq in Korea. • Arena is working to try to obtain approval of Belviq in Europe.

36. Serotonin Receptors • 7 families 5HT1 through 5HT7. • 14 subtypes of 5HT receptors. • Belviq is a 5HT2c serotonin receptor agonist… it “stimulates” the 5HT2c receptor).

37. 5HT serotonin receptor subtypes • 5HT 2c receptor : decreases appetite • 5HT 2b receptor : aortic/mitral valve regurgitation • 5HT 2a receptor : hallucinations (LSD) • 5HT 1b receptor : pulmonary artery hypertension

38. Phentermine/ dexfenfluramine • “Phen-fen” was taken off the market due to heart valve (5HT2b receptor) and pulmonary artery hypertension(5HT1b receptor) problems related to dexfenfluramine. Phentermine is still available as a pill for weight loss. • Belviq stimulates mainly the 5HT2c receptor, and has minimal effect on the 5HT2b receptor , the 5HT2a receptor, and the 5HT1b receptor.

39. Echocardiograms • Over 20,000 echocardiograms were performed during the Bloom, Blossom, and Bloom DM studies. Just under 8,000 total patients in those 3 studies.

40. Circulation Article • Circulation: Cardiovascular Imaging • Neil Weissman et al • Spring 2013 • “In 3 prospective placebo-controlled trials with integrated data for 5,249 patients, the rate of echocardiographic valvulopathy was similar with lorcaserin and placebo.”

41. BELVIQ MECHANISM • Belviq (and serotonin) stimulates 5HT2c serotonin receptors on the POMC/CART neurons (pro-opiomelanocortin/cocaine and amphetamine regulated transcript neurons) in the arcuate nucleus , which causes release of alpha MSH (melanocyte stimulating hormone) which then acts on MC3/4 receptors in the paraventricular nucleus to decrease appetite. Brain dopamine levels fall.

42. Lorcaserin (Belviq) is in the lower right corner of this diagram …

43. Belviq is not a “fat burner”.

44. Belviq decreases appetite.

45. 5HT2c knockout mice lack the 5HT2c receptor and overeat.

46. BELVIQ PHARMACOLOGY • Half life is 11 hours. • T max is 2.3 hours. • One 10mg tablet twice a day with or without food. • Steady state within 3 days. • Concentrates in the brain. • Mild to moderate cytochrome P450 2d6 inhibitor.

47. Unlikely to be an interaction between Belviq and warfarin. • Belviq is a moderate inhibitor of cytochrome p450 2d6. • S-warfarin is metabolized by cytochrome p450 2c9. • R-warfarin is metabolized by cytochrome p450 1A2 and 3A4.

48. Likely to be an interaction between Belviq and tamoxifen. • Belviq is a CYP2D6 inhibitor. • Tamoxifenis metabolized by CYP2D6 to active (helpful) metabolites. • Belviq could decrease the amount of the active (helpful) metabolites of tamoxifen. • If you are on tamoxifen, avoid 2D6 inhibitors like Prozac, Paxil, Wellbutrin, Cymbalta, Zoloft, and Benadryl. • Celexa, Lexapro, and Effexor are not 2D6 inhibitors.

49. BELVIQ METABOLISM Initial metabolism is in the liver by multiple pathways, and then 92% is recovered in the urine. • Use with caution if renal impairment is moderate. Do not use if renal impairment is severe (creatinine clearance less than 30) or if on dialysis. • No dose change for mild to moderate liver disease. Not studied in severe liver disease.

50. Belly Fat (intraabdominal fat): waist circumference often correlates with risk of diabetes and heart disease.