Peptide Therapeutics: it‘s All in the Delivery

• Klerman EB , AdlerGK, JinM, MaliszewskiAM, BrownEN. A statistical model of diurnal variation in human growth hormone. Am. J. Physiol. Endocrinol. Metab.285(5), E1118–E1126 (2003).
   PubMed Web of Science ®Google Scholar
• Hindmarsh PC . The impact of hormone physiology on clinical practice with reference to two papers spanning 40 years of endocrinology. Arch. Dis. Child.90(11), 1144–1147 (2005).
   PubMed Web of Science ®Google Scholar
• Frolik CA , BlackEC, CainRLet al. Anabolic and catabolic bone effects of human parathyroid hormone (1–34) are predicted by duration of hormone exposure. Bone 33(3), 372–379 (2003).
   PubMed Web of Science ®Google Scholar
• Basu A , ManCD, BasuR, ToffoloG, CobelliC, RizzaRA. Effects of Type 2 diabetes on insulin secretion, insulin action, glucose effectiveness, and postprandial glucose metabolism. Diabetes Care32(5), 866–872 (2009).
   PubMed Web of Science ®Google Scholar
• Rave K , BottS, HeinemannLet al. Time-action profile of inhaled insulin in comparison with subcutaneously injected insulin lispro and regular human insulin. Diabetes Care 28(5), 1077–1082 (2005).
   PubMed Web of Science ®Google Scholar
• Bolli GB , LuzioS, MarzottiSet al. Comparative pharmacodynamic and pharmacokinetic characteristics of subcutaneous insulin glulisine and insulin aspart prior to a standard meal in obese subjects with Type 2 diabetes. Diabetes Obes. Metab. 13(3), 251–257 (2011).
   PubMed Web of Science ®Google Scholar
• Steiner S , HompeschM, PohlRet al. A novel insulin formulation with a more rapid onset of action. Diabetologia 51(9), 1602–1606 (2008).
   PubMed Web of Science ®Google Scholar
• Salinari S , BertuzziA, AsnaghiS, GuidoneC, MancoM, MingroneG. First-phase insulin secretion restoration and differential response to glucose load depending on the route of administration in Type 2 diabetic subjects after bariatric surgery. Diabetes Care32(3), 375–380 (2009).
   PubMed Web of Science ®Google Scholar
• Lefèbvre PJ , PaolissoG, ScheenAJ, HenquinJC. Pulsatility of insulin and glucagon release: physiological significance and pharmacological implications. Diabetologia30(7), 443–452 (1987).
   PubMed Web of Science ®Google Scholar
• Ihlo CA , LauritzenT, SturistJ, SkyggebjergO, ChristiansenJS, LarsenT. Treatment pharmacokinetics and pharmacodynamics of different modes of insulin pump delivery. A randomized, controlled study comparing subcutaneous and intravenous administration of insulin aspart. Diabetic Med.28(2), 230–236 (2011).
   PubMed Web of Science ®Google Scholar
• Wasan KM . The role of lymphatic transport in enhancing oral protein and peptide drug delivery. Drug Dev. Ind. Pharm.28(9), 1047–1058 (2002).
   PubMed Web of Science ®Google Scholar
• Mahato RI Narang AS, Thoma L, Miller DD. Emerging trends in oral delivery of peptide and protein drugs. Crit. Rev. Ther. Drug Carrier Syst.20(2–3), 153–214 (2003).
   PubMed Web of Science ®Google Scholar
• Hamman JH , EnslinGM, KotzeAF. Oral delivery of peptide drugs. Biodrugs19(3), 165–177 (2005).
   PubMed Web of Science ®Google Scholar
• Aungst BJ . Intestinal permeation enhancers. J. Pharm. Sci.89(4), 429–442 (2000).
   PubMed Web of Science ®Google Scholar
• Sharma P , VarmaMVS, ChawlaHPS, PanchagnulaR. Absorption enhancement, mechanistic and toxicity studies of medium chain fatty acids, cyclodextrins and bile salts as peroral absorption enhancers. Il Farmaco60(11–12), 884–893 (2005).
   PubMedGoogle Scholar
• Mehta N , EricksonK, SternWet al. nighttime dosing with an oral calcitonin tablet significantly reduces plasma CTx-1. J. Bone Miner. Res. 24(Suppl. 1), (2009).
   Google Scholar
• Binkley N , BologneseM, Sidorowicz-BialynickaAet al. A Phase 3 trial of the efficacy and safety of oral recombinant calcitonin: the ORACAL trial. J. Bone Miner. Res. doi:10.1002/jbmr.1602 (2012) (In Press).
   Web of Science ®Google Scholar
• Karsdal MA , ByrjalsenI, RiisBJ, ChristiansenC. Investigation of the diurnal variation in bone resorption for optimal drug delivery and efficacy in osteroporosis with oral calcitonin. BMC Clin. Pharmacol.8(12), (2008).
   Google Scholar
• Karsdal MA , ByrjalsenI, AziraMet al. Influence of food intake on the bioavailability and efficacy of oral calcitonin. Br. J. Clin. Pharmacol. 67(4), 413–420 (2009).
   PubMed Web of Science ®Google Scholar
• Karsdal MA , ByrjalsenI, RiisBJ, ChristiansenC. Optimizing bioavailability of oral administration of small peptides through pharmacokinetic and pharmacodynamic parameters: the effect of water and timing of meal intake on oral delivery of salmon calcitonin. BMC Clin. Pharmacol.8(5), (2008).
   Google Scholar
• Kapitza C , ZijlstraE, HeinemannL, CastelliMC, RileyG, HeiseT. Oral insulin: a comparison with subcutaneous regular human insulin in patients with Type 2 diabetes. Diabetes Care33(6), 1288–1290 (2010).
   PubMed Web of Science ®Google Scholar
• Clement S , DandonaP, StillJG, KosuticG. Oral modified insulin (HIM2) in patients with Type 1 diabetes mellitus: results from a phase I/II clinical trial. Metabolism53(1), 54–58 (2004).
   PubMed Web of Science ®Google Scholar
• Khedkar A , IyerH, AnandAet al. A dose range finding study of novel oral insulin (IN-105) under fed conditions in Type 2 diabetes mellitus subjects. Diabetes Obes. Metab. 12(8), 659–664 (2010).
   PubMed Web of Science ®Google Scholar
• Goodman MP . Are all estrogens created equal? A review of oral vs. transdermal therapy. J. Womens Health21(2), 161–169 (2012).
   PubMed Web of Science ®Google Scholar
• Kalluri H , BangaAK. Transdermal delivery of proteins. AAPS PharmSciTech12(1), 431–441 (2011).
   PubMed Web of Science ®Google Scholar
• Prausnitz MR , LangerR. Transdermal drug delivery. Nat. Biotechnol.26(11), 1261–1268 (2008).
   PubMed Web of Science ®Google Scholar
• Patel YR . Altea Therapeutics Transdermal PassPort™ system: freedom from insulin injections for superior diabetes management. In: Drug Delivery in Diabetes: Making Effective Treatment Tolerable. Furness G (Ed.). ONdrugDelivery Ltd, Newtimber, UK, 4–7 (2006).
   Google Scholar
• Shalom SI , KenanY, MatsumotoT, NeerR. Repetitive rapid delivery of pharmacologically-active hPTH 1–34 across human skin without injection. Presented at: 30th ASMBR Annual Meeting. Montreal, Canada, 12–16 September 2008.
   Google Scholar
• Daddona PE , MatrianoJA, MandemaJ, Maa Y-F. Parathyroid hormone (1-34)-coated microneedle patch system: clinical pharmacokinetics and pharmacodynamics for treatment of osteoporosis. Pharm. Res.28(1), 159–165 (2011).
   PubMed Web of Science ®Google Scholar
• Jadhav KR , GambhireMN, ShaikhI, KadamV, PisalSS. Nasal drug delivery system – factors affecting and applications. Curr. Drug Ther.2(1), 27–38 (2007).
   Google Scholar
• Pires A , FortunaA, AlvesG, FalcãoA. Intranasal drug delivery: how, why and what for? J. Pharm. Pharmaceut. Sci.12(3), 288–311 (2009).
   PubMed Web of Science ®Google Scholar
• Henkin RI . Intranasal insulin: from nose to brain. Nutrition26(6), 624–633 (2010).
   PubMed Web of Science ®Google Scholar
• Ozsoy Y , GungorS, CevherE. Nasal delivery of high molecular weight drugs. Molecules14, 3754–3779 (2009).
   PubMed Web of Science ®Google Scholar
• Leary AC , StoteRM, CussenK, O‘BrienJ, LearyWP, BuckleyB. Pharmacokinetics and pharmacodynamics of intranasal insulin administered to patients with Type 1 diabetes: a preliminary study. Diabetes Technol. Ther.8(1), 81–88 (2006).
   PubMed Web of Science ®Google Scholar
• Leary AC , DowlingM, CussenK, O‘BrienJ, StoteRM. Pharmacokinetics and pharmacodynamics of intranasal insulin spray (Nasulin™) administered to healthy male volunteers: influence of the nasal cycle. J. Diabetes Sci. Technol.2(6), 1054–1060 (2008).
   PubMedGoogle Scholar
• Henkin RI . Inhaled insulin – intrapulmonary, intranasal, and other routes of administration: mechanisms of action. Nutrition26(1), 33–39 (2010).
   PubMed Web of Science ®Google Scholar
• Grim M , CarlsonBM. Alkaline phosphatase and dipeptidyldipeptidase IV staining of tissue components of skeletal muscle: a comparative study. J. Histochem. Cytochem.38(12), 1907–1912 (1990).
   PubMed Web of Science ®Google Scholar
• Ryan JW . Peptidase enzymes of the pulmonary vascular surface. Am. J. Physiol. Lung Cell Mol. Biol.257(2), L53–L60 (1989).
   PubMedGoogle Scholar
• Cefalu WT . Concept, strategies, and feasibility of noninvasive insulin delivery. Diabetes Care27(1), 239–246 (2004).
   PubMed Web of Science ®Google Scholar
• Siekmeier R , ScheuchG. Systematic treatment by inhalation of macromolecules – principles, problems, and examples. J. Physiol. Pharmacol.59(Suppl. 6), 53–79 (2008).
   PubMed Web of Science ®Google Scholar
• Rave K , HeiseT, PfütznerA, BossAH. Coverage of postprandial blood glucose excursions with inhaled Technosphere insulin in comparison to subcutaneously injected regular human insulin in subjects with Type 2 diabetes. Diabetes Care30(9), 2307–2308 (2007).
   PubMed Web of Science ®Google Scholar
• Rave K , HeiseT, HeinemannL, BossAH. Inhaled Technosphere insulin in comparison to subcutaneous regular human insulin: time action profile and variability in subjects with Type 2 diabetes. J. Diabetes Sci. Technol.2(2), 205–212 (2008).
   PubMedGoogle Scholar
• Heinemann L , HeiseT. Current status of the development of inhaled insulin. Br. J. Diabetes Vasc. Dis.4(5), 295–301 (2004).
   Google Scholar
• Bergenstal RM , KapsnerPL, RendellMSet al. Comparative efficacy and safety of AFRESA™ and a rapid-acting analog both given with glargine in subjects with T1DM in a 52-week study. Presented at: American Diabetes Association‘s 69th Scientific Sessions. New Orleans, LA, USA, 5–7 June 2009.
   Google Scholar
• Lorber D , HowardCP, RenH, RossiterA, BossAH. Reduced incidence and frequency of hypoglycemia in an integrated analysis from clinical trials of subjects with Type 2 diabetes using prandial inhaled Technosphere® insulin. Presented at: AACE 19th Annual Meeting and Clinical Congress. Boston, MA, USA, 21–25 April 2010.
   Google Scholar
• Raskin P , PhillipsMD, RossiterA, BossAH, RichardsonPC. A1C and hypoglycemia in patients with Type 2 diabetes mellitus incorporating prandial inhaled Technosphere insulin into their usual antihyperglycemic regimen vs continuing their usual antihyperglycemic regimen. Presented at: American Diabetes Association‘s 70th Scientific Sessions. Orlando, FL, USA, 25–29 June 2010.
   Google Scholar
• Rosenstock J , LorberDL, GnudiLet al. Prandial inhaled insulin plus basal insulin glargine versus twice daily biaspart insulin for Type 2 diabetes: a multicentre randomised trial. Lancet 375(9733), 2244–2253 (2010).
   PubMed Web of Science ®Google Scholar
• Comulada AL , RenardE, NakanoMet al. Efficacy and safety of AIR inhaled insulin compared to insulin lispro in patients with Type 1 diabetes mellitus in a 6-month, randomized, noninferiority trial. Diabetes Technol. Ther. 11(Suppl. 2), S17–S25 (2009).
   PubMed Web of Science ®Google Scholar
• Garg SK , MathieuC, RaisNet al. Two-year efficacy and safety of AIR inhaled insulin in patients with Type 1 diabetes: an open-label randomized controlled trial. Diabetes Technol. Ther. 11(Suppl. 2), S5–S16 (2009).
   PubMed Web of Science ®Google Scholar
• Hollander PA , KrasnerA, KliozeS, SchwartzP, DugganW. Body weight changes associated with insulin therapy. Diabetes Care30(10), 2508–2510 (2007).
   PubMed Web of Science ®Google Scholar
• Moses RG , BartleyP, LuntHet al. Treatment safety and efficacy of inhaled insulin (AERx iDMS1) compared with subcutaneous insulin therapy in patients with Type 1 diabetes: 1-year data from a randomized, parallel group trial. Diabetic Med. 26(3), 260–267 (2009).
   PubMed Web of Science ®Google Scholar
• D‘Alessio DA , VahlTP. Glucagon-like peptide 1: evolution of an incretin into a treatment for diabetes. Am. J. Physiol. Endocrinol. Metab.286(6), E882–E890 (2004).
   PubMed Web of Science ®Google Scholar
• Zander M , MadsbadS, MadsenJL, HolstJJ. Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and beta-cell function in Type 2 diabetes: a parallel-group study. Lancet359(9309), 824–830 (2002).
   PubMed Web of Science ®Google Scholar
• Vilsb⊘ll T , Agers⊘H, KrarupT, Holst.JJ. Similar elimination rates of glucagon-like peptide-1 in obese Type 2 diabetic patients and healthy subjects. J. Clin. Endocrinol. Metab.88(1), 220–224 (2003).
   PubMed Web of Science ®Google Scholar
• Vrang N , LarsenPJ. Preproglucagon derived peptides GLP-1, GLP-2 and oxyntomodulin in the CNS: role of peripherally secreted and centrally produced peptides. Prog. Neurobiol.92(3), 442–462 (2010).
   PubMed Web of Science ®Google Scholar
• Leone-Bay A , GrantM, GreeneSet al. Evaluation of novel particles as an inhalation system for GLP-1. Diabetes Obes. Metab. 11(11), 1050–1059 (2009).
   PubMed Web of Science ®Google Scholar
• Marino MT , CostelloD, BaughmanRet al. Pharmacokinetics and pharmacodynamics of inhaled GLP-1 (MKC253): proof of concept studies in healthy normal volunteers and in patients with Type 2 diabetes. Clin. Pharmacol. Ther. 88(2), 243–250 (2010).
   PubMed Web of Science ®Google Scholar
• Vilsb⊘ll T , Toft-Nielsen M-B, Krarup T, Madsbad S, Dinesen B, Hulst JJ. Evaluation of b-cell secretory capacity using glucagon-like peptide-1. Diabetes Care23(6), 807–812 (2000).
   PubMed Web of Science ®Google Scholar
• Körner M , StöckliM, WaserB, ReubiJC. GLP-1 receptor expression in human tumors and human normal tissues: potential for in vivo targeting. J. Nuclear Med.48(5), 736–743 (2007).
   PubMed Web of Science ®Google Scholar
• Steinert RE , PollerB, CastelliMC, DreweJ, BeglingerC. Oral administration of glucagon-like peptide 1 or peptide YY 3–36 affects food intake in healthy males. Am. J. Clin. Nutr.92(4), 810–817 (2010).
   PubMed Web of Science ®Google Scholar
• Beglinger C , PollerB, ArbitEet al. Pharmacokinetics and pharmacodynamic effects of oral GLP-1 and PYY3–36: a proof-of-concept study in healthy subjects. Clin. Pharmacol. Ther. 84(4), 469–474 (2008).
   Web of Science ®Google Scholar
• Leone-Bay A . Mimicking endogenous peptide secretion by inhalation. Presented at: 21st American Peptide Symposium ‘Peptides: Breaking Away‘. Bloomington, IN, USA, 7–12 June 2009.
   Google Scholar
• Leone-Bay A , BaughmanR, SmutneyC, KocinskyJ. Innovation in drug delivery by inhalation. In: Orally Inhaled and Nasal Drug Delivery: Innovations from Major Delivery System Developers. Furness G (Ed.). ONdrugDelivery Ltd, Newtimber, UK, 4–8 (2010).
   Google Scholar

Websites

• Tarsa advances OSTORA NDA filing through $28M Series B financing. www.news-medical.net/news/20120317/Tarsa-advances-OSTORA-NDA-filing-through-2428M-Series-B-financing.aspx
   Google Scholar
• Palmer A. Oppenheimer 22nd Annual Healthcare Conference. www.unigene.com/wp-content/uploads/2011/11/UniGene_1.pdf
   Google Scholar
• Atlanta Business Chronicle. $60M later, biotech Altea calls it quits. www.bizjournals.com/atlanta/print-edition/2011/12/09/60m-later-biotech-altea-calls-it-quits.html?s=print
   Google Scholar
• ClinincalTrials.gov. A study to evaluate the effect of nasal insulin on postprandial glycemic control in Type 2 diabetic patients. http://clinicaltrials.gov/ct2/show/NCT00624767
   Google Scholar
• ClinincalTrials.gov. A study of nasal PYY3–36 and placebo for weight loss in obese subjects. http://clinicaltrials.gov/ct2/show/NCT00537420
   Google Scholar
• ClinincalTrials.gov. Study to evaluate effect of intranasal teriparatide on bone mineral density in postmenopausal women with low BMD. http://clinicaltrials.gov/ct2/show/NCT00624481
   Google Scholar
• New Hampshire Business Review. CPEX drops Nasulin development. www.nhbr.com/businessnews/statenews/704288–257/cpex-drops-nasulin-development.html
   Google Scholar