Acta Scientific Pharmaceutical Sciences (ASPS)(ISSN: 2581-5423)

Review Article Volume 5 Issue 10

The Current Landscape of Long-acting Growth Hormone Therapy

Srushti Sodha*

University of the Sciences in Philadelphia, Philadelphia, USA

*Corresponding Author: Srushti Sodha, University of the Sciences in Philadelphia, Philadelphia, USA.

Received: August 05, 2021; Published: September 06, 2021

Abstract

  Growth hormone deficiency is a rare disease characterized by short stature, delay in maturation and growth of children due to poor development of the skeletal tissue. The current market for GHD treatment consists of once daily injections as a replacement therapy to growth hormone. The review commences by summarizing the existing FDA approved formulations, with their indications, challenges and dosage regimen. Furthermore, we have reviewed the progress and challenges associated with the long acting formulations undergoing clinical trials currently. Various research projects have implemented alternative routes of delivery such as pulmonary and transdermal, or used nano-systems for controlled release of hGH, thereby reducing the dosing frequency. Our aim is to shed some light on these approaches, while also evaluating their feasibility of traversing from bench to bedside. In this rapidly transient field, we aim to emphasize this review on the research published during or after 2015.

Keywords: Long-acting hGH; PEGylation; Fusion Proteins; Lipidation

References

  1. S R Rose. “Management options for pediatric growth hormone deficiency”. Expert Opinion on Orphan Drugs 2 (2019).
  2. B C Cunningham and J A Wells. “High-resolution epitope mapping of hGH-receptor interactions by alanine-scanning mutagenesis”. Science (80-. ) 4908 (1989): 1081-1085.
  3. Y Cai., et al. “Developments in human growth hormone preparations: sustained-release, prolonged half-life, novel injection devices, and alternative delivery routes”. International Journal of Nanomedicine 9 (2014): 3527.
  4. M T Larsen., et al. “Albumin-based drug delivery: harnessing nature to cure disease”. Molecular Therapy 1 (2016): 3.
  5. U Fiedler., et al. “Recombinant binding proteins targeting her2 and serum albumin, and their uses”. Google Patents, 07-Jun (2018).
  6. J Cho., et al. “Generation of therapeutic protein variants with the human serum albumin binding capacity via site-specific fatty acid conjugation”. Scientific Report1 (2017): 18041.
  7. E Adabi., et al. “Evaluation of an albumin-binding domain protein fused to recombinant human IL-2 and its effects on the bioactivity and serum half-life of the cytokine”. Iranian Biomedical Journal 2 (2017): 77.
  8. EM Bech., et al. “Chemical Strategies for Half-Life Extension of Biopharmaceuticals: Lipidation and Its Alternatives”. ACS Publications (2018).
  9. P Thygesen., et al. “Preclinical characterisation of NNC0195-0092, a long-acting GH”. in 15th European Congress of Endocrinology 32 (2012).
  10. M H Rasmussen., et al. “A reversible albumin-binding growth hormone derivative is well tolerated and possesses a potential once-weekly treatment profile”. The Journal of Clinical Endocrinology and Metabolism10 (2014): E1819-E1829.
  11. MH Rasmussen., et al. “Reversible albumin-binding GH possesses a potential once-weekly treatment profile in adult growth hormone deficiency”. The Journal of Clinical Endocrinology and Metabolism3 (20186): 988-998.
  12. MH Rasmussen., et al. “Sc Injections of a Reversible Albumin-Binding GH Derivative (NNC0195-0092) in Adult Subjects with GH Deficiency is Well Tolerated”. in ESPE 2014 (2014): 82.
  13. N Zuckerman-Levin., et al. “A Novel Reversible Albumin-Binding GH Derivative Possesses a Promising Once-Weekly Treatment Profile in Children with GH Deficiency”. in 54th Annual ESPE (2015): 84.
  14. C A R T-Cells. “New phase 2 data for somapacitan demonstrate its potential as an efficacious once-weekly treatment for childhood growth hormone deficiency”.
  15. “Substance Name: Somapacitan USAN:INN” (2019).
  16. R A Ningrum., et al. “Overproduction, purification and characterization of human interferon alpha2a-human serum albumin fusion protein produced in methilotropic yeast Pichia pastoris”. in Journal of Physics: Conference Series1 (2017): 12013.
  17. B Guan., et al. “Effects of co‐overexpression of secretion helper factors on the secretion of a HSA fusion protein (IL2‐HSA) in pichia pastoris”. Yeast11 (2016): 587-600.
  18. S Xia., et al. “Construction and expression of releasable glucagon-like peptide-1 and human serum albumin fusion proteins and preliminary evaluation of their pharmacodynamics and pharmacokinetics”. Military Medical Research 8 (2015): 587-592.
  19. Cohen-Barak., et al. “Safety, pharmacokinetic and pharmacodynamic properties of TV-1106, a long-acting GH treatment for GH deficiency”. European Journal of Endocrinology 5 (2015): 541-551.
  20. N Ashkenazi., et al. “Safety and PK/PD correlation of TV-1106, a recombinant fused human albumin-growth hormone, following repeat dose administration to monkeys”. Growth Hormone and IGF Research 30 (2016): 16-21.
  21. Cohen‐Barak., et al. “Assessment of the Pharmacokinetics, Pharmacodynamics, and Safety of Single Doses of TV‐1106, a Long‐Acting Growth Hormone, in Healthy Japanese and Caucasian Subjects”. Clinical Pharmacology in Drug Development 4 (2017): 331-342.
  22. Cohen-Barak., et al. “The Pharmacokinetics and Pharmacodynamics of TV-1106, a Once Weekly GH Supplement: Results from a Phase 2 Study of TV-1106 in Adults with GH Deficiency”. in 54th Annual ESPE 84 (2015).
  23. L Hou., et al. “Comparative pharmacokinetics and pharmacodynamics of a PEGylated recombinant human growth hormone and daily recombinant human growth hormone in growth hormone-deficient children”. Drug Design, Development and Therapy 10 (2016): 13.
  24. Y Guan., et al. “A long‐acting pegylated recombinant human growth hormone (Jintrolong®) in healthy adult subjects: Two single‐dose trials evaluating safety, tolerability and pharmacokinetics”. Journal of Clinical Pharmacy and Therapeutics 5 (2018): 640-646.
  25. M Karbasian., et al. “Design, development and evaluation of PEGylated rhGH with preserving its bioactivity at highest level after modification”. International Journal of Pharmaceutics 557 (2019): 9-17.
  26. X Luo., et al. “A long‐acting pegylated recombinant human growth hormone (Jintrolong®) in healthy adult subjects: Two single‐dose trials evaluating safety, tolerability and pharmacokinetics”. European Journal of Endocrinology 2 (2017): 195-205.
  27. , et al. “In vitro and in vivo characterization of MOD-4023, a long-acting carboxy-terminal peptide (CTP)-modified human growth hormone”. Molecular Pharmaceutics 13.2 (2016): 631-639.
  28. WG Kramer., et al. “Pharmacokinetics, Pharmacodynamics, and Safety of a Long‐Acting Human Growth Hormone (MOD‐4023) in Healthy Japanese and Caucasian Adults”. Clinical Pharmacology in Drug Development 5 (2018): 554-563.
  29. N Zelinska., et al. “Long-Acting C-Terminal Peptide-Modified hGH (MOD-4023): Results of a Safety and Dose-Finding Study in GHD Children”. The Journal of Clinical Endocrinology and Metabolism5 (2017): 1578-1587.
  30. C J Strasburger., et al. “MOD-4023, a long-acting carboxy-terminal peptide-modified human growth hormone: results of a Phase 2 study in growth hormone-deficient adults”. European Journal of Endocrinology 3 (2017): 283-294.
  31. K Sprogøe., et al. “The rationale and design of TransCon Growth Hormone for the treatment of growth hormone deficiency”. Endocrine Connection8 (2017): R171-R181.
  32. P Chatelain., et al. “A randomized phase 2 study of long-acting TransCon GH vs daily GH in childhood GH deficiency”. The Journal of Clinical Endocrinology and Metabolism5 (2017): 1673-1682.
  33. D Gilfoyle., et al. “A first-in-man phase 1 trial for long-acting TransCon Growth Hormone”. Growth Hormone and IGF Research 39 (2018): 34-39.
  34. C Höybye., et al. “A phase 2 trial of long-acting TransCon growth hormone in adult GH deficiency”. Endocrine Connection3 (2017): 129-138.
  35. V Schellenberger., et al. “A recombinant polypeptide extends the in vivo half-life of peptides and proteins in a tunable manner”. Nature Biotechnology12 (2009): 1186.
  36. J L Cleland., et al. “A novel long‐acting human growth hormone fusion protein (vrs‐317): enhanced in vivo potency and half‐life”. Journal of Pharmaceutical Sciences 8 (2012): 2744-2754.
  37. W V Moore., et al. “A randomized safety and efficacy study of somavaratan (VRS-317), a long-acting rhGH, in pediatric growth hormone deficiency”. The Journal of Clinical Endocrinology and Metabolism 3 (2016): 1091-1097.
  38. BS Miller., et al. “3-year safety and efficacy Update of the VERTICAL and VISTA trials of somavaratan (VRS-317), a long-acting rhGH, in children with Growth Hormone Deficiency (GHD)”. in 19th European Congress of Endocrinology 49 (2017).
  39. J S Patil and S Sarasija. “Pulmonary drug delivery strategies: A concise, systematic review”. Lung India: Official Organ of Indian Chest Society's 1 (2012): 44.
  40. YZ Li., et al. “Inhalable microparticles as carriers for pulmonary delivery of thymopentin-loaded solid lipid nanoparticles”. Pharmaceutical Research 9 (2010): 1977-1986.
  41. F Andrade., et al. “Nanocarriers for pulmonary administration of peptides and therapeutic proteins”. Nanomedicine1 (2011): 123-141.
  42. J S Patton., et al. “Methods and compositions for pulmonary delivery of insulin”. Google Patents 21-Apr- (2009).
  43. L Illum., et al. “CriticalSorbTM: A novel efficient nasal delivery system for human growth hormone based on Solutol HS15”. Journal of Control Release1 (2012): 194-200.
  44. D Kilian., et al. “Vesicular carriers for skin drug delivery: the PheroidTM technology”. Current Pharmaceutical Design 20 (2015): 2758-2770.
  45. D Steyn., et al. “Nasal delivery of recombinant human growth hormone: in vivo evaluation with PheroidTM technology and N-trimethyl chitosan chloride”. Journal of Pharmacy and Pharmaceutical Sciences2 (2010): 263-273.
  46. JJ Arnold., et al. “Reestablishment of the nasal permeability barrier to several peptides following exposure to the absorption enhancer tetradecyl-β-D-maltoside”. Journal of Pharmaceutical Sciences (2010).
  47. M Ameri., et al. “Human growth hormone delivery with a microneedle transdermal system: preclinical formulation, stability, delivery and PK of therapeutically relevant doses”. Pharmaceutics2 (2014): 220-234.
  48. Y Song., et al. “Transdermal delivery of human growth hormone via laser-generated micropores”. Drug Delivery and Translational Research 2 (2018): 450-460.
  49. S J Kim and C W Kim. “Development and characterization of sodium hyaluronate microparticle-based sustained release formulation of recombinant human growth hormone prepared by Spray-Drying”. Journal of Pharmaceutical Sciences 2 (2016): 613-622.
  50. D Y Yoon and JC Kim. “In vivo residence duration of human growth hormone loaded in nanogels comprising cinnamoyl alginate, cinnamoyl Pluronic F127 and cinnamoyl poly (ethylene glycol)”. International Journal of Pharmaceutics 1-2 (2016): 229-236.
  51. B Deutel., et al. “In vitro characterization of insulin containing thiomeric microparticles as nasal drug delivery system”. European Journal of Pharmaceutical Sciences 81 (2016): 157-161.
  52. Y Gao., et al. “Sustained release of recombinant human growth hormone from bioresorbable poly (ester urea) nanofibers”. ACS Macro Letter8 (2017): 875-880.
  53. B Ramalapa., et al. “Protein-polysaccharide complexes for enhanced protein delivery in hyaluronic acid templated calcium carbonate microparticles”. Journal of Materials Chemistry B35 (2017): 7360-7368.
  54. “Common Injection challenges”.
  55. “Nutropin Depot somatropin (rDNA origin) for injectable suspension” (2019).
  56. ICIS news. “US firms announce discontinuance of ‘Nutropin Depot’” (2004).
  57. “Genentech and Alkermes Announce Decision to Discontinue Commercialization of Nutropin Depot” (2004).
  58. W R Strohl. “Fusion proteins for half-life extension of biologics as a strategy to make biobetters”. BioDrugs4 (2015): 215-239.
  59. H Hatakeyama., et al. “The polyethyleneglycol dilemma: advantage and disadvantage of PEGylation of liposomes for systemic genes and nucleic acids delivery to tumors”. Biological and Pharmaceutical Bulletin 6 (2013): 892-899.
  60. S B van Witteloostuijn., et al. “Half‐life extension of biopharmaceuticals using chemical methods: alternatives to PEGylation”. ChemMedChem22 (2016): 2474-2495.
  61. P Hazra., et al. “Development of a process to manufacture PEGylated orally bioavailable insulin”. Biotechnology Progress 6 (2010): 1695-1704.
  62. H Shi., et al. “Site-specific PEGylation of Human Growth Hormone by Mutated Sortase A”. Chemical Research in Chinese Universities3 (2018): 428-433.
  63. A Grigoletto., et al. “Chemical and Enzymatic Site Specific PEGylation of hGH: The Stability and in vivo Activity of PEG‐N‐Terminal‐hGH and PEG‐Gln141‐hGH Conjugates”. Macromolecular Bioscience 1 (2016): 50-56.
  64. D Bobo., et al. “Nanoparticle-based medicines: a review of FDA-approved materials and clinical trials to date”. Pharmaceutical Research 10 (2016): 2373-2387.
  65. “Humatrope® (Somatropin, rDNA Origin, for Injection)”.
  66. “GENOTROPIN:somatropin rDNA origin”.
  67. “Saizen®somatropin (rDNA origin) for injection.,For subcutaneous or intramuscular injection”.
  68. “Norditropin® (somatropin) injection, for subcutaneous use” (2019).
  69. “TEV-TROPIN®somatropin (rDNA origin) for injection” (2019).
  70. “OMNITROPETM somatropin (rDNA origin) injection., for subcutaneous use” (2019).

Citation

Citation: Srushti Sodha. “The Current Landscape of Long-acting Growth Hormone Therapy". Acta Scientific Pharmaceutical Sciences 5.10 (2020): 09-20.

Copyright

Copyright: © 2021 Srushti Sodha. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.




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