PF-05231023, a long-acting FGF21 analogue, decreases body weight by reduction of food intake in non-human primates

Journal of Pharmacokinetics and Pharmacodynamics

Volumn 43, Issue 4, 2016, Pages 411-425

  Thompson, W Clayton ^a,c   Zhou, Yingjiang ^a,b   Talukdar, Saswata ^a,b   Musante, Cynthia J ^a  

^a PFIZER INC   (United States)

^b MERCK RESEARCH LABORATORIES   (United States)

^c NONE   (United States)

Author keywords

Body weight; Energy balance; FGF21; K PD; Mathematical Model; Non human primate; Obesity

Indexed keywords

ANTIOBESITY AGENT; FIBROBLAST GROWTH FACTOR 21; PF 05231023; UNCLASSIFIED DRUG; FIBROBLAST GROWTH FACTOR; MONOCLONAL ANTIBODY; PF-05231023;

ANIMAL EXPERIMENT; ARTICLE; BODY COMPOSITION; CALORIC DENSITY; COMPARATIVE STUDY; CONTROLLED STUDY; DOSE RESPONSE; ENERGY BALANCE; ENERGY EXPENDITURE; FOOD INTAKE; IC50; MACACA FASCICULARIS; MALE; MATHEMATICAL MODEL; MOUSE; NONHUMAN; PRIORITY JOURNAL; WEIGHT REDUCTION; ANIMAL; BIOLOGICAL MODEL; BODY WEIGHT; DRUG EFFECTS; EATING; ENERGY METABOLISM; INTRAVENOUS DRUG ADMINISTRATION; METABOLISM; OBESITY;

ANIMALS; ANTI-OBESITY AGENTS; ANTIBODIES, MONOCLONAL, HUMANIZED; BODY WEIGHT; DOSE-RESPONSE RELATIONSHIP, DRUG; EATING; ENERGY METABOLISM; FIBROBLAST GROWTH FACTORS; INJECTIONS, INTRAVENOUS; MACACA FASCICULARIS; MALE; MODELS, BIOLOGICAL; OBESITY;

EID: 84978036565     PISSN: 1567567X     EISSN: 15738744     Source Type: Journal    
DOI: 10.1007/s10928-016-9481-1     Document Type: Article

References (49)

1. Narayan KMV, Boyle JP, Geiss LS, Saaddine JB, Thompson TJ (2006) Impact of recent increase in incidence on future diabetes burden: U.S., 2005–2050. Diabetes Care 29:2114–2116
2. Scully T (2012) Diabetes in numbers. Nature 485:S2–S3
3. James PT, Leach R, Kalamara E, Shayeghi M (2001) The worldwide obesity epidemic. Obes Res 9:228S–233S
4. Levin BE (2000) The obesity epidemic: metabolic imprinting on genetically susceptible neural circuits. Obes Res 8:342–347
5. Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS, Marks JS (2003) Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA 289:76–79
6. Ogden CL, Carroll MD, Kit BK, Flegal KM (2012) Prevalence of obesity in the United States, 2009–2010. NCHS Data Brief 2012:1–8
7. Kharitonenkov A, Shiyanova TL, Koester A, Ford AM, Micanovic R, Galbreath EJ et al (2005) FGF-21 as a novel metabolic regulator. J Clin Investig 115:1627–1635
8. Adams AC, Halstead CA, Hansen BC, Irizarry AR, Martin JA, Myers SR et al (2013) LY2405319, an engineered FGF21 variant, improves the metabolic status of diabetic monkeys. PLoS One 8:e65763
9. Foltz IN, Hu S, King C, Wu X, Yang C, Wang W et al (2012) Treating diabetes and obesity with an FGF21-mimetic antibody activating the klotho/FGFR1c receptor complex. Sci Transl Med 4:162ra153
10. Long YC, Kharitonenkov A (2011) Hormone-like fibroblast growth factors and metabolic regulation. BBA 1812:791–795
11. Potthoff MJ, Kliewer SA, Mangelsdorf DJ (2012) Endocrine fibroblast growth factors 15/19 and 21: from feast to famine. Genes Dev 26:312–324
12. Weng Y, Chabot JR, Bernardo B, Yan Q, Zhu Y, Brenner MB et al (2015) Pharmacokinetics (PK), pharmacodynamics (PD) and integrated PK/PD modeling of a novel long acting FGF21 clinical candidate PF-05231023 in diet-induced obese and leptin-deficient obese mice. PLoS One 10:e0119104
13. Ding X, Boney-Montoya J, Owen BM, Bookout AL, Coate KC, Mangelsdorf DJ, Kliewer SA (2012) β-klotho Is required for fibroblast growth factor 21 effects on growth and metabolism. Cell Metab 16:387–393
14. Holland WL, Adams AC, Brozinick JT, Bui HH, Miyauchi Y, Kusminski CM et al (2013) An FGF21-adiponectin-ceramide axis controls energy expenditure and insulin action in mice. Cell Metab 17:790–797
15. Lee DV, Li D, Yan Q, Zhu Y, Goodwin B, Calle R et al (2014) Fibroblast growth factor 21 improves insulin sensitivity and synergizes with insulin in human adipose stem cell-derived (hASC) adipocytes. PLoS One 9:e111767
16. Lin Z, Tian H, Lam KSL, Lin S, Hoo RCL, Konishi M et al (2013) Adiponectin mediates the metabolic effects of FGF21 on glucose homeostasis and insulin sensitivity in mice. Cell Metab 17:779–789
17. Adams AC, Coskun T, Irizarry Rovira AR, Schneider MA, Raches DW, Micanovic R et al (2012) Fundamentals of FGF19 & FGF21 action in vitro and in vivo. PLoS One 7:e38438
18. Huang J, Ishino T, Chen G, Rolzin P, Osothprarop TF, Retting K et al (2013) Development of a novel long-acting antidiabetic FGF21 mimetic by targeted conjugation to a scaffold antibody. J Pharmacol Exp Ther 346:270–280
19. Kim HW, Lee JE, Cha JJ, Hyun YY, Kim JE, Lee MH et al (2013) Fibroblast growth factor 21 improves insulin resistance and ameliorates renal injury in db/db mice. Endocrinology 154:3366–3376
20. Bookout AL, de Groot MHM, Owen BM, Lee S, Gautron L, Lawrence HL et al (2013) FGF21 regulates metabolism and circadian behavior by acting on the nervous system. Nat Med 19:1147–1152
21. Owen BM, Ding X, Morgan DA, Coate KC, Bookout AL, Rahmouni K et al (2014) FGF21 acts centrally to induce sympathetic nerve activity, energy expenditure, and weight loss. Cell Metab 20:670–677
22. Coskun T, Bina HA, Schneider MA, Dunbar JD, Hu CC, Chen Y et al (2008) Fibroblast growth factor 21 corrects obesity in mice. Endocrinology 149:6018–6027
23. Kharitonenkov A, Beals JM, Micanovic R, Strifler BA, Rathnachalam R, Wroblewski VJ et al (2013) Rational design of a fibroblast growth factor 21-based clinical candidate, LY2405319. PLoS One 8:e58575
24. Xu J, Lloyd DJ, Hale C, Stanislaus S, Chen M, Sivits G et al (2008) Fibroblast growth factor 21 reverses hepatic steatosis, increases energy expenditure, and improves insulin sensitivity in diet-induced obese mice. Diabetes 58:250–259
25. Gaich G, Chien JY, Fu H, Glass LC, Deeg MA, Holland WL et al (2013) The effects of LY2405319, an FGF21 analog, in obese human subjects with type 2 diabetes. Cell Metab 18:333–340
26. Talukdar S, Zhou Y, Li D, Rossulek M, Dong J, Somayaji V, Weng Y et al (2016) A long-acting FGF21 molecule, PF-05231023, decreases body weight and improves lipid profile in non-human primates and type 2 diabetic subjects. Cell Metab 23(3):427–440
27. Selimkhanov J, Thompson WC, Patterson TA, Hadcock JR, Scott DO, Mauer TS, Musante CJ (2016) Evaluation of a mathematical model of rat body weight regulation in application to caloric restriction and drug treatment studies. PLoS One 11:e0155674
28. Bauer SA, Arndt TP, Leslie KE, Pearl DL, Turner PV (2011) Obesity in rhesus and cynomolgus macaques: a comparative review of the condition and its implications for research. Comp Med 61:514–526
29. Jayo JM, Shively CA, Kaplan JR, Manuck SB (1993) Effects of exercise and stress on body fat distribution in male cynomolgus monkeys. Int J Obes 17:597–604
30. Shively CA, Wallace JM (2001) Social status, social stress, and fat distribution in primates. International Textbook of Obesity, pp 203–211
31. Guo J, Hall KD (2009) Estimating the continuous-time dynamics of energy and fat metabolism in mice. PLoS Comput Biol 5:e1000511
32. Guo J, Hall KD (2011) Predicting changes of body weight, body fat, energy expenditure and metabolic fuel selection in C57BL/6 Mice. PLoS One 6:e15961
33. Hall KD, Chow CC (2011) Estimating changes in free-living energy intake and its confidence interval. Am J Clin Nutr 94:66–74
34. Gennemark P, Jansson-Lfmark R, Hyberg G, Wigstrand M, Kakol-Palm D, Hkansson P et al (2013) A modeling approach for compounds affecting body composition. J Pharmacokinet Pharmacodyn 40:651–667
35. Göbel B, Sanghvi A, Hall KD (2014) Quantifying energy intake changes during obesity pharmacotherapy. Obesity 22:2105–2108
36. Calories in 100 g Apples and Nutrition Facts http://www.fatsecret.com/calories-nutrition/usda/apples?portionid=58449&portionamount=100.000. Accessed 16 May 2016
37. Household USDA Foods Fact Sheet: Infant Rice Cereal http://www.fns.usda.gov/sites/default/files/HHFS_INFANT-RICE-CEREAL_110241Nov2012. Accessed 16 May 2016
38. Chow CC, Hall KD (2008) The dynamics of human body weight change. PLoS Comput Biol 4:e1000045
39. Jacqmin P, Snoeck E, van Schaick EA, Gieschke R, Pillai P, Steimer JL, Girard P (2006) Modelling response time profiles in the absence of drug concentrations: definition and performance evaluation of the K-PD model. J Pharmacokinet Pharmacodyn 34:57–85
40. Banks HT, Tran HT (2009) Mathematical and experimental modeling of physical and biological processes. Chapman Hall/CRC Press, Cambridge, p 298
41. Banks HT, Kenz Z, Thompson WC (2012) An extension of RSS-based model comparison tests for weighted least squares. Intl J Pure Appl Math 79:155–183
42. Banks HT, Holm K, Robbins D (2010) Standard error computations for uncertainty quantification in inverse problems: asymptotic theory vs bootstrapping. Math Comput Model 52:1610–1625
43. Heymsfield SB, Gonzalez MCC, Shen W, Redman L, Thomas D (2014) Weight loss composition is one-fourth fat-free mass: a critical review and critique of this widely cited rule. Obes Rev 15:310–321
44. Hall KD (2006) Computational model of in vivo human energy metabolism during semistarvation and refeeding, AJP. Endocrinol Metab 291:E23–E37
45. Hall KD (2010) Predicting metabolic adaptation, body weight change, and energy intake in humans. AJP Endocrinol Metab 298:E449–E466
46. Sarruf DA, Thaler JP, Morton GJ, German J, Fischer JD, Ogimoto K, Schwartz MW (2010) Fibroblast growth factor 21 action in the brain increases energy expenditure and insulin sensitivity in obese rats. Diabetes 59:1817–1824
47. Forbes GB (1987) Lean body mass-body fat interrelationships in humans. Nutr Rev 45:225–231
48. Summers L, Clingerman KJ, Yang X (2012) Validation of a body condition scoring system in rhesus macaques (Macaca mulatta): assessment of body composition by using dual-energy X-ray absorptiometry. J Am Assoc Lab Anim Sci 51:88–93
49. Power ML, Toddes B, Koutsos L (2012) Nutrient requirements and dietary husbandry principles for captive nonhuman primates. In: Abee C, Mansfield K, Tardif S, Morris T (eds) Nonhuman Primates in Biomedical Research. Elsevier, New York