Lorcaserin: drug profile and illustrative model of the regulatory challenges of weight-loss drug development

References

• Bray GA. Medical consequences of obesity. J. Clin. Endocrinol. Metab.89(6), 2583–2589 (2004).
   PubMed Web of Science ®Google Scholar
• Kushner RF, Roth JL. Assessment of the obese patient. Endocrinol. Metab. Clin. North Am.32(4), 915–933 (2003).
   PubMed Web of Science ®Google Scholar
• Powers KA, Rehrig ST, Jones DB. Financial impact of obesity and bariatric surgery. Med. Clin. North Am.91(3), 321–338, ix (2007).
   PubMedGoogle Scholar
• Tsai AG, Wadden TA. Systematic review: an evaluation of major commercial weight loss programs in the United States. Ann. Intern. Med.142(1), 56–66 (2005).
   PubMed Web of Science ®Google Scholar
• Bays HE. ‘Sick fat,’ metabolic disease, and atherosclerosis. Am. J. Med.122(1 Suppl.), S26–S37 (2009).
   PubMed Web of Science ®Google Scholar
• Bays H, Abate N, Chandalia M. Adiposopathy: sick fat causes high blood sugar, high blood pressure, and dyslipidemia. Future Cardiol.1(1), 39–59 (2005).
   PubMedGoogle Scholar
• Bays H, Ballantyne C. Adiposopathy: why do adiposity and obesity cause metabolic disease? Future Lipidol.1(4), 389–420 (2006).
   Web of Science ®Google Scholar
• Bays H, Blonde L, Rosenson R. Adiposopathy: how do diet, exercise, weight loss and drug therapies improve metabolic disease? Expert Rev. Cardiovasc. Ther.4(6), 871–895 (2006).
   PubMedGoogle Scholar
• Bays HE, Rodbard RW, Schorr AB, González-Campoy JM. Adiposopathy: treating pathogenic adipose tissue to reduce cardiovascular disease risk. Curr. Treat. Options Cardiovasc. Med.9(4), 259–271 (2007).
   PubMedGoogle Scholar
• Bays H. Phentermine, topiramate and their combination for the treatment of adiposopathy (‘sick fat’) and metabolic disease. Expert Rev. Cardiovasc. Ther.8(12), 1777–1807 (2010).
   PubMedGoogle Scholar
• Bays HE, Gonzalez-Campoy JM, Bray GA et al. Pathogenic potential of adipose tissue and metabolic consequences of adipocyte hypertrophy and increased visceral adiposity. Expert Rev. Cardiovasc. Ther.6(3), 343–368 (2008).
   PubMedGoogle Scholar
• Greenway FL, Caruso MK. Safety of obesity drugs. Expert Opin. Drug Saf.4(6), 1083–1095 (2005).
   PubMedGoogle Scholar
• Bays H. Perspective: is bias behind the lack of new obesity drug therapies? Clin. Endocrinol. News5(8), 10 (2010).
   Google Scholar
• Bays HE. Lorcaserin and adiposopathy: 5-HT2C agonism as a treatment for ‘sick fat’ and metabolic disease. Expert Rev. Cardiovasc. Ther.7(11), 1429–1445 (2009).
   PubMedGoogle Scholar
• Coleman E. FDA briefing document. NDA 22529 Lorqess (lorcaserin hydrochloride) Tablets, 10 mg Sponsor: Arena Pharmaceuticals Advisory Committee (2010).
   Google Scholar
• Smith SR, Prosser WA, Donahue DJ, Morgan ME, Anderson CM, Shanahan WR. Lorcaserin (APD356), a selective 5-HT(2C) agonist, reduces body weight in obese men and women. Obesity (Silver Spring)17(3), 494–503 (2009).
   PubMed Web of Science ®Google Scholar
• Dattilo AM, Kris-Etherton PM. Effects of weight reduction on blood lipids and lipoproteins: a meta-analysis. Am. J. Clin. Nutr.56(2), 320–328 (1992).
   PubMed Web of Science ®Google Scholar
• Smith SR, Weissman NJ, Anderson CM et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N. Engl. J. Med.363(3), 245–256 (2010).
   PubMed Web of Science ®Google Scholar
• Smith SR, Weissman NJ, Stubbe S, Anderson CM, Shanahan WR. Lorcaserin reduces body weight in obese and overweight subjects: behavioral modification and lorcaserin for overweight and obese management; the BLOOM Trial. Abstract Poster Presentation no. 96. Presented at: American Diabetes Association 69th Scientific Session. New Orleans, LA, USA, 5–9 June 2009.
   Google Scholar
• Bays H. Adiposopathy: the endocannabinoid system as a therapeutic treatment target for dysfunctional ‘sick’ fat. CJHP19(1), 32–39 (2007).
   Google Scholar
• Fong TM, Heymsfield SB. Cannabinoid-1 receptor inverse agonists: current understanding of mechanism of action and unanswered questions. Int. J. Obes. (Lond).33(9), 947–955 (2009).
   PubMed Web of Science ®Google Scholar
• Topol EJ, Bousser MG, Fox KA et al. Rimonabant for prevention of cardiovascular events (CRESCENDO): a randomised, multicentre, placebo-controlled trial. Lancet376(9740), 517–523 (2010).
   PubMed Web of Science ®Google Scholar
• No authors listed. Rimonabant: marketing authorization suspended… at last: withdrawal. Half-measures. Prescrire Int.18(100), 61 (2009).
   Google Scholar
• Rosenzweig-Lipson S, Dunlop J, Marquis KL. 5-HT2c receptor agonists as an innovative approach for psychiatric disorders. Drug News Perspect.20(9), 565–571 (2007).
   PubMedGoogle Scholar
• Beck AT, Steer RA, Ball R, Ranieri W. Comparison of Beck Depression Inventories-IA and -II in psychiatric outpatients. J. Pers. Assess.67(3), 588–597 (1996).
   PubMed Web of Science ®Google Scholar
• CDC. Cardiac valvulopathy associated with exposure to fenfluramine or dexfenfluramine: US Department of Health and Human Services interim public health recommendations, November 1997. MMWR Morb. Mortal. Wkly. Rep.46, 1061–1066 (1997).
   PubMedGoogle Scholar
• Contrera JF, Matthews EJ, Kruhlak NL, Benz RD. Estimating the safe starting dose in Phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose. Regul. Toxicol. Pharmacol.40(3), 185–206 (2004).
   PubMed Web of Science ®Google Scholar
• Wade JM, Juneja P, MacKay AW et al. Synergistic impairment of glucose homeostasis in ob/ob mice lacking functional serotonin 2c receptors. Endocrinology149(3), 955–961 (2008).
   PubMed Web of Science ®Google Scholar
• Nonogaki K, Kaji T, Ohba Y, Sumii M, Wakameda M, Tamari T. Serotonin 5-HT2c receptor-independent expression of hypothalamic NOR1, a novel modulator of food intake and energy balance, in mice. Biochem. Biophys. Res. Commun.386(2), 311–315 (2009).
   PubMedGoogle Scholar
• Hayashi A, Sonoda R, Kimura Y et al. Antiobesity effect of YM348, a novel 5-HT2c receptor agonist, in Zucker rats. Brain Res.1011(2), 221–227 (2004).
   PubMedGoogle Scholar
• Thomsen WJ, Grottick AJ, Menzaghi F et al. Lorcaserin, a novel selective human 5-hydroxytryptamine 2c agonist: in vitro and in vivo pharmacological characterization. J. Pharmacol. Exp. Ther.325(2), 577–587 (2008).
   PubMed Web of Science ®Google Scholar
• Gross L, Dreyfuss Y. Spontaneous tumors in Sprague–Dawley and Long–Evans rats and in their F1 hybrids: carcinogenic effect of total-body x-irradiation. Proc. Natl Acad. Sci. USA76(11), 5910–5913 (1979).
   PubMedGoogle Scholar
• Cohen SM, Klaunig J, Meek ME et al. Evaluating the human relevance of chemically induced animal tumors. Toxicol. Sci.78(2), 181–186 (2004).
   PubMed Web of Science ®Google Scholar
• Ghoshal A, Preisegger KH, Takayama S, Thorgeirsson SS, Snyderwine EG. Induction of mammary tumors in female Sprague–Dawley rats by the food-derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and effect of dietary fat. Carcinogenesis15(11), 2429–2433 (1994).
   PubMed Web of Science ®Google Scholar
• Welsch CW, Nagasawa H. Prolactin and murine mammary tumorigenesis: a review. Cancer Res.37(4), 951–963 (1977).
   PubMed Web of Science ®Google Scholar
• Welsch CW, Nagasawa H, Meites J. Increased incidence of spontaneous mammary tumors in female rats with induced hypothalamic lesions. Cancer Res.30(9), 2310–2313 (1970).
   PubMedGoogle Scholar
• Bjerre Knudsen L, Madsen LW, Andersen S et al. Glucagon-like peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation. Endocrinology151(4), 1473–1486 (2010).
   PubMed Web of Science ®Google Scholar
• Soffritti M, Belpoggi F, Degli Esposti D et al. First experimental demonstration of the multipotential carcinogenic effects of aspartame administered in the feed to Sprague–Dawley rats. Environ. Health Perspect.114(3), 379–385 (2006).
   PubMed Web of Science ®Google Scholar
• Yang Q. Gain weight by ‘going diet?’ Artificial sweeteners and the neurobiology of sugar cravings: Neuroscience 2010. Yale J. Biol. Med.83(2), 101–108 (2010).
   PubMedGoogle Scholar
• James WP, Caterson ID, Coutinho W et al. Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N. Engl. J. Med.363(10), 905–917 (2010).
   PubMed Web of Science ®Google Scholar
• Sawbridge DT, Fitzgerald R. ‘Lazy, slothful and indolent’: medical and social perceptions of obesity in Europe to the eighteenth century. Vesalius15(2), 59–70 (2009).
   PubMedGoogle Scholar
• Bluher M. Adipose tissue dysfunction in obesity. Exp. Clin. Endocrinol. Diabetes117(6), 241–250 (2009).
   PubMed Web of Science ®Google Scholar
• Bays HE, Gonzalez-Campoy JM, Henry RR et al. Is adiposopathy (sick fat) an endocrine disease? Int. J. Clin. Pract.62(10), 1474–1483 (2008).
   PubMed Web of Science ®Google Scholar
• Kummar S, Rubinstein L, Kinders R et al. Phase 0 clinical trials: conceptions and misconceptions. Cancer J.14(3), 133–137 (2008).
   PubMed Web of Science ®Google Scholar
• Collins S, Surwit RS. Pharmacologic manipulation of ob expression in a dietary model of obesity. J. Biol. Chem.271(16), 9437–9440 (1996).
   PubMed Web of Science ®Google Scholar
• Li X, Grundy SM, Patel SB. Obesity in db and ob animals leads to impaired hepatic very low density lipoprotein secretion and differential secretion of apolipoprotein B-48 and B-100. J. Lipid Res.38(7), 1277–1288 (1997).
   PubMedGoogle Scholar
• Akagiri S, Naito Y, Ichikawa H et al. A mouse model of metabolic syndrome; increase in visceral adipose tissue precedes the development of fatty liver and insulin resistance in high-fat diet-fed male KK/Ta mice. J. Clin. Biochem. Nutr.42(2), 150–157 (2008).
   PubMedGoogle Scholar
• Kobayashi K, Forte TM, Taniguchi S, Ishida BY, Oka K, Chan L. The db/db mouse, a model for diabetic dyslipidemia: molecular characterization and effects of Western diet feeding. Metabolism49(1), 22–31 (2000).
   PubMed Web of Science ®Google Scholar
• Strauss V, Wiemer J, Leibold E et al. Influence of strain and sex on the metabolic profile of rats in repeated dose toxicological studies. Toxicol. Lett.191(1), 88–95 (2009).
   PubMedGoogle Scholar
• Clause BT. The Wistar rat as a right choice: establishing mammalian standards and the ideal of a standardized mammal. J. Hist. Biol.26(2), 329–349 (1993).
   PubMed Web of Science ®Google Scholar
• Kurtz TW, Morris RC, Pershadsingh HA. The Zucker fatty rat as a genetic model of obesity and hypertension. Hypertension13(6 Pt 2), 896–901 (1989).
   PubMed Web of Science ®Google Scholar
• Cusin I, Rohner-Jeanrenaud F, Stricker-Krongrad A, Jeanrenaud B. The weight-reducing effect of an intracerebroventricular bolus injection of leptin in genetically obese fa/fa rats. Reduced sensitivity compared with lean animals. Diabetes45(10), 1446–1450 (1996).
   PubMed Web of Science ®Google Scholar
• Li S, Zhang HY, Hu CC et al. Assessment of diet-induced obese rats as an obesity model by comparative functional genomics. Obesity (Silver Spring)16(4), 811–818 (2008).
   PubMed Web of Science ®Google Scholar