Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

New therapeutic agents for acromegaly

Nature Reviews Endocrinology volume 12, pages 90–98 (2016)Cite this article

Subjects

Key Points

  • Available medical therapies for acromegaly are limited by moderate and variable efficacy, the need for life-long monthly intramuscular and/or deep subcutaneous depot, or thrice-daily subcutaneous injections, as well as adverse effects

  • DG3173, an injectable somatostatin receptor ligand (SRL) in development, selectively suppresses secretion of growth hormone and seems to have negligible inhibitory effects on insulin secretion, which suggests it has a favourable hyperglycaemic adverse effect profile

  • The investigational agent CAM2029 slowly releases octreotide from a liquid crystal matrix and is administered subcutaneously via thin, prefilled syringes, which facilitates ease of use and delivery

  • Oral octreotide capsules (which are not yet approved) maintain biochemical control and improve symptoms in most patients who respond to injectable SRL therapy; they have a safety profile similar to that of injectable octreotide (except for injection-site reactions)

  • ATL1103, an antisense oligonucleotide in development, reduces serum levels of insulin-like growth factor 1 by blocking synthesis of growth hormone receptor, but might require frequent injections to maintain efficacy

  • Further investigation into new formulations of currently approved molecules, as well as those in clinical development, should optimize outcomes of medical therapy in patients with acromegaly

Abstract

The currently available somatostatin receptor ligands (SRLs) and growth hormone (GH) antagonists are used to control levels of GH and insulin-like growth factor 1 (IGF-1) in patients with acromegaly. However, these therapies are limited by wide variations in efficacy, associated adverse effects and the need for frequent injections. A phase III trial of oral octreotide capsules demonstrated that this treatment can safely sustain suppressed levels of GH and IGF-1 and reduce the severity of symptoms in patients with acromegaly previously controlled by injectable SRL therapy, with the added benefit of no injection-site reactions. Phase I and phase II trials of the pan-selective SRL DG3173, the liquid crystal octreotide depot CAM2029 and an antisense oligonucleotide directed against the GH receptor have shown that these agents can be used to achieve biochemical suppression in acromegaly and have favourable safety profiles. This Review outlines the need for new therapeutic agents for patients with acromegaly, reviews clinical trial data of investigational agents and considers how these therapies might best be integrated into clinical practice.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: GH secretion.
Figure 2: Mechanism of action of octreotide capsules.
Figure 3: Mechanism of action of ATL1103.

Similar content being viewed by others

References

  1. Clemmons, D. R. The relative roles of growth hormone and IGF-1 in controlling insulin sensitivity. J. Clin. Invest. 113, 25–27 (2004).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Ribeiro-Oliveira, A. Jr & Barkan, A. The changing face of acromegaly — advances in diagnosis and treatment. Nat. Rev. Endocrinol. 8, 605–611 (2012).

    Article  CAS  PubMed  Google Scholar 

  3. Melmed, S. Medical progress: acromegaly. N. Engl. J. Med. 355, 2558–2573 (2006).

    Article  CAS  PubMed  Google Scholar 

  4. Colao, A., Ferone, D., Marzullo, P. & Lombardi, G. Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr. Rev. 25, 102–152 (2004).

    Article  CAS  PubMed  Google Scholar 

  5. Drange, M. R., Fram, N. R., Herman-Bonert, V. & Melmed, S. Pituitary tumor registry: a novel clinical resource. J. Clin. Endocrinol. Metab. 85, 168–174 (2000).

    CAS  PubMed  Google Scholar 

  6. Kannan, S. & Kennedy, L. Diagnosis of acromegaly: state of the art. Expert Opin. Med. Diagn. 7, 443–453 (2013).

    Article  CAS  PubMed  Google Scholar 

  7. Sherlock, M. et al. Mortality in patients with pituitary disease. Endocr. Rev. 31, 301–342 (2010).

    Article  PubMed  Google Scholar 

  8. Sherlock, M. et al. A paradigm shift in the monitoring of patients with acromegaly: last available growth hormone may overestimate risk. J. Clin. Endocrinol. Metab. 99, 478–485 (2014).

    Article  CAS  PubMed  Google Scholar 

  9. Ayuk, J. et al. Growth hormone and pituitary radiotherapy, but not serum insulin-like growth factor-I concentrations, predict excess mortality in patients with acromegaly. J. Clin. Endocrinol. Metab. 89, 1613–1617 (2004).

    Article  CAS  PubMed  Google Scholar 

  10. Holdaway, I. M., Rajasoorya, R. C. & Gamble, G. D. Factors influencing mortality in acromegaly. J. Clin. Endocrinol. Metab. 89, 667–674 (2004).

    Article  CAS  PubMed  Google Scholar 

  11. Jane, J. A. Jr et al. Endoscopic transsphenoidal surgery for acromegaly: remission using modern criteria, complications, and predictors of outcome. J. Clin. Endocrinol. Metab. 96, 2732–2740 (2011).

    Article  CAS  PubMed  Google Scholar 

  12. Giustina, A. et al. Expert consensus document: a consensus on the medical treatment of acromegaly. Nat. Rev. Endocrinol. 10, 243–248 (2014).

    Article  CAS  PubMed  Google Scholar 

  13. Katznelson, L. et al. Acromegaly: an Endocrine Society Clinical Practice Guideline. J. Clin. Endocrinol. Metab. 99, 3933–3951 (2014).

    Article  CAS  PubMed  Google Scholar 

  14. Marko, N. F., LaSota, E., Hamrahian, A. H. & Weil, R. J. Comparative effectiveness review of treatment options for pituitary microadenomas in acromegaly. J. Neurosurg. 117, 522–538 (2012).

    Article  PubMed  Google Scholar 

  15. Sherlock, M., Woods, C. & Sheppard, M. C. Medical therapy in acromegaly. Nat. Rev. Endocrinol. 7, 291–300 (2011).

    Article  CAS  PubMed  Google Scholar 

  16. Carmichael, J. D., Bonert, V. S., Nuno, M., Ly, D. & Melmed, S. Acromegaly clinical trial methodology impact on reported biochemical efficacy rates of somatostatin receptor ligand treatments: a meta-analysis. J. Clin. Endocrinol. Metab. 99, 1825–1833 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Caron, P. J. et al. Tumor shrinkage with lanreotide autogel 120 mg as primary therapy in acromegaly: results of a prospective multicenter clinical trial. J. Clin. Endocrinol. Metab. 99, 1282–1290 (2014).

    Article  CAS  PubMed  Google Scholar 

  18. Giustina, A. et al. Meta-analysis on the effects of octreotide on tumor mass in acromegaly. PLoS ONE 7, e36411 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Lamberts, S. W., van der Lely, A. J., de Herder, W. W. & Hofland, L. J. Octreotide. N. Engl. J. Med. 334, 246–254 (1996).

    Article  CAS  PubMed  Google Scholar 

  20. Colao, A. et al. Twelve months of treatment with octreotide-LAR reduces joint thickness in acromegaly. Eur. J. Endocrinol. 148, 31–38 (2003).

    Article  CAS  PubMed  Google Scholar 

  21. Freda, P. U. Somatostatin analogs in acromegaly. J. Clin. Endocrinol. Metab. 87, 3013–3018 (2002).

    Article  CAS  PubMed  Google Scholar 

  22. Ben-Shlomo, A., Sheppard, M. C., Stephens, J. M., Pulgar, S. & Melmed, S. Clinical, quality of life, and economic value of acromegaly disease control. Pituitary 14, 284–294 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Giustina, A., Karamouzis, I., Patelli, I. & Mazziotti, G. Octreotide for acromegaly treatment: a reappraisal. Expert Opin. Pharmacother. 14, 2433–2447 (2013).

    Article  CAS  PubMed  Google Scholar 

  24. Korytnaya, E. & Barkan, A. Pharmacological treatment of acromegaly: its place in the overall therapeutic approach. J. Neurooncol. 117, 415–420 (2014).

    Article  PubMed  Google Scholar 

  25. Ayuk, J., Stewart, S. E., Stewart, P. M. & Sheppard, M. C. Long-term safety and efficacy of depot long-acting somatostatin analogs for the treatment of acromegaly. J. Clin. Endocrinol. Metab. 87, 4142–4146 (2002).

    Article  CAS  PubMed  Google Scholar 

  26. Holdaway, I. M., Bolland, M. J. & Gamble, G. D. A meta-analysis of the effect of lowering serum levels of GH and IGF-I on mortality in acromegaly. Eur. J. Endocrinol. 159, 89–95 (2008).

    Article  CAS  PubMed  Google Scholar 

  27. Mercado, M. et al. Successful mortality reduction and control of comorbidities in patients with acromegaly followed at a highly specialized multidisciplinary clinic. J. Clin. Endocrinol. Metab. 99, 4438–4446 (2014).

    Article  CAS  PubMed  Google Scholar 

  28. Biermasz, N. R. Pituitary gland: mortality in acromegaly reduced with multimodal therapy. Nat. Rev. Endocrinol. 10, 708–710 (2014).

    Article  PubMed  Google Scholar 

  29. Colao, A. et al. Pasireotide versus octreotide in acromegaly: a head-to-head superiority study. J. Clin. Endocrinol. Metab. 99, 791–799 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Gadelha, M. R. et al. Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, Phase 3 trial. Lancet Diabetes Endocrinol. 2, 875–884 (2014).

    Article  CAS  PubMed  Google Scholar 

  31. Henry, R. R. et al. Hyperglycemia associated with pasireotide: results from a mechanistic study in healthy volunteers. J. Clin. Endocrinol. Metab. 98, 3446–3453 (2013).

    Article  CAS  PubMed  Google Scholar 

  32. Tritos, N. A. The role of pasireotide in the treatment of acromegaly. Lancet Diabetes Endocrinol. 2, 855–856 (2014).

    Article  CAS  PubMed  Google Scholar 

  33. Afargan, M. et al. Novel long-acting somatostatin analog with endocrine selectivity: potent suppression of growth hormone but not of insulin. Endocrinology 142, 477–486 (2001).

    Article  CAS  PubMed  Google Scholar 

  34. Roberts, J., Linden, M., Cervin, C. & Tiberg, F. Randomized study demonstrating that octreotide fluid crystal provides sustained octreotide bioavailability and similar IGF1 suppression to octreotide LAR (sandostatin LAR) in healthy volunteers. [abstract OR17-6], Presented at the Endocrine Society's 96th Annual Meeting and Exposition (2014).

  35. Plockinger, U. et al. DG3173 (somatoprim), a unique somatostatin receptor subtypes 2-, 4- and 5-selective analogue, effectively reduces GH secretion in human GH-secreting pituitary adenomas even in octreotide non-responsive tumours. Eur. J. Endocrinol. 166, 223–234 (2012).

    Article  CAS  PubMed  Google Scholar 

  36. US National Library of Medicine. The effect of subcutaneous infusions of 3 doses of DG3173 on growth hormone levels in untreated acromegalics. ClinicalTrials.gov[online], (2015).

  37. Tuvia, S. et al. Oral octreotide absorption in human subjects: comparable pharmacokinetics to parenteral octreotide and effective growth hormone suppression. J. Clin. Endocrinol. Metab. 97, 2362–2369 (2012).

    Article  CAS  PubMed  Google Scholar 

  38. Tuvia, S. et al. A novel suspension formulation enhances intestinal absorption of macromolecules via transient and reversible transport mechanisms. Pharm. Res. 31, 2010–2021 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Melmed, S. et al. Safety and efficacy of oral octreotide in acromegaly: results of a multicenter Phase III trial. J. Clin. Endocrinol. Metab. 100, 1699–1708 (2015).

    Article  CAS  PubMed  Google Scholar 

  40. Melmed, S., Biermasz, N. R., Trainer, P. J., Patou, G. & Haviv, A. Determinants of oral octreotide capsules efficacy in acromegaly. [abstract OR 09-3], Presented at the 17th International Congress of Endocrinology and The Endocrine Society's 97th Annual Meeting and Exposition (2015).

  41. Trainer, P. J. et al. Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N. Engl. J. Med. 342, 1171–1177 (2000).

    Article  CAS  PubMed  Google Scholar 

  42. van der Lely, A. J. et al. Long-term safety of pegvisomant in patients with acromegaly: comprehensive review of 1288 subjects in ACROSTUDY. J. Clin. Endocrinol. Metab. 97, 1589–1597 (2012).

    Article  CAS  PubMed  Google Scholar 

  43. Freda, P. U. et al. Long-term treatment with pegvisomant as monotherapy in patients with acromegaly: experience from acrostudy. Endocr. Pract. 21, 1–32 (2014).

    Google Scholar 

  44. Dias, N. & Stein, C. A. Antisense oligonucleotides: basic concepts and mechanisms. Mol. Cancer Ther. 1, 347–355 (2002).

    Article  CAS  PubMed  Google Scholar 

  45. Tachas, G. et al. A GH receptor antisense oligonucleotide inhibits hepatic GH receptor expression, IGF-I production and body weight gain in normal mice. J. Endocrinol. 189, 147–154 (2006).

    Article  CAS  PubMed  Google Scholar 

  46. Trainer, P. J. et al. A Phase 2 study of antisense oligonucleotide therapy directed at the GH receptor demonstrates lowering of serum IGF-I in patients with acromegaly. [abstract OR09-1], Presented at the Endocrine Society's 97th Annual Meeting and Exposition (2015).

  47. Melmed, S. Acromegaly pathogenesis and treatment. J. Clin. Invest. 119, 3189–3202 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Chanson, P. & Salenave, S. Acromegaly. Orphanet J. Rare Dis. 3, 17 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  49. Giustina, A. & Veldhuis, J. D. Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human. Endocr. Rev. 19, 717–797 (1998).

    CAS  PubMed  Google Scholar 

  50. Casanueva, F. F. et al. Growth hormone-releasing hormone as an agonist of the ghrelin receptor GHS-R1a. Proc. Natl Acad. Sci. USA 105, 20452–20457 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Murray, R. D. et al. Central and peripheral actions of somatostatin on the growth hormone–IGF-I axis. J. Clin. Invest. 114, 349–356 (2004).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Pokrajac, A., Frystyk, J., Flyvbjerg, A. & Trainer, P. J. Pituitary-independent effect of octreotide on IGF-I generation. Eur. J. Endocrinol. 160, 543–548 (2009).

    Article  CAS  PubMed  Google Scholar 

  53. Lesche, S., Lehmann, D., Nagel, F., Schmid, H. A. & Schulz, S. Differential effects of octreotide and pasireotide on somatostatin receptor internalization and trafficking in vitro. J. Clin. Endocrinol. Metab. 94, 654–661 (2009).

    Article  CAS  PubMed  Google Scholar 

  54. Shimon, I. & Melmed, S. Genetic basis of endocrine disease: pituitary tumor pathogenesis. J. Clin. Endocrinol. Metab. 82, 1675–1681 (1997).

    CAS  PubMed  Google Scholar 

  55. Puig Domingo, M. Treatment of acromegaly in the era of personalized and predictive medicine. Clin. Endocrinol. (Oxf.) 83, 3–14 (2015).

    Article  CAS  Google Scholar 

  56. Murray, R. D. & Melmed, S. A critical analysis of clinically available somatostatin analog formulations for therapy of acromegaly. J. Clin. Endocrinol. Metab. 93, 2957–2968 (2008).

    Article  CAS  PubMed  Google Scholar 

  57. Cuevas-Ramos, D. et al. A structural and functional acromegaly classification. J. Clin. Endocrinol. Metab. 100, 122–131 (2015).

    Article  CAS  PubMed  Google Scholar 

  58. Taboada, G. F. et al. Quantitative analysis of somatostatin receptor subtypes (1–5) gene expression levels in somatotropinomas and correlation to in vivo hormonal and tumor volume responses to treatment with octreotide LAR. Eur. J. Endocrinol. 158, 295–303 (2008).

    Article  CAS  PubMed  Google Scholar 

  59. Colao, A. et al. Partial surgical removal of growth hormone-secreting pituitary tumors enhances the response to somatostatin analogs in acromegaly. J. Clin. Endocrinol. Metab. 91, 85–92 (2006).

    Article  CAS  PubMed  Google Scholar 

  60. Bhayana, S., Booth, G. L., Asa, S. L., Kovacs, K. & Ezzat, S. The implication of somatotroph adenoma phenotype to somatostatin analog responsiveness in acromegaly. J. Clin. Endocrinol. Metab. 90, 6290–6295 (2005).

    Article  CAS  PubMed  Google Scholar 

  61. Brzana, J., Yedinak, C. G., Gultekin, S. H., Delashaw, J. B. & Fleseriu, M. Growth hormone granulation pattern and somatostatin receptor subtype 2A correlate with postoperative somatostatin receptor ligand response in acromegaly: a large single center experience. Pituitary 16, 490–498 (2013).

    Article  CAS  PubMed  Google Scholar 

  62. Puig-Domingo, M. et al. Magnetic resonance imaging as a predictor of response to somatostatin analogs in acromegaly after surgical failure. J. Clin. Endocrinol. Metab. 95, 4973–4978 (2010).

    Article  CAS  PubMed  Google Scholar 

  63. Adelman, D. T., Liebert, K. J., Nachtigall, L. B., Lamerson, M. & Bakker, B. Acromegaly: the disease, its impact on patients, and managing the burden of long-term treatment. Int. J. Gen. Med. 6, 31–38 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  64. Alexopoulou, O. et al. Efficacy and tolerability of lanreotide Autogel therapy in acromegalic patients previously treated with octreotide LAR. Eur. J. Endocrinol. 151, 317–324 (2004).

    Article  CAS  PubMed  Google Scholar 

  65. Salvatori, R., Woodmansee, W. W., Molitch, M., Gordon, M. B. & Lomax, K. G. Lanreotide extended-release aqueous-gel formulation, injected by patient, partner or healthcare provider in patients with acromegaly in the United States: 1-year data from the SODA registry. Pituitary 17, 13–21 (2014).

    Article  CAS  PubMed  Google Scholar 

  66. Atmaca, A. & Erbas, T. Lipoatrophy induced by subcutaneous administration of octreotide in the treatment of acromegaly. Exp. Clin. Endocrinol. Diabetes 113, 340–343 (2005).

    Article  CAS  PubMed  Google Scholar 

  67. Cocoman, A. & Murray, J. Recognizing the evidence and changing practice on injection sites. Br. J. Nurs. 19, 1170–1174 (2010).

    Article  PubMed  Google Scholar 

  68. Shimon, I., Rubinek, T., Hadani, M. & Alhadef, N. PTR-3173 (somatoprim), a novel somatostatin analog with affinity for somatostatin receptors 2, 4 and 5 is a potent inhibitor of human GH secretion. J. Endocrinol. Invest. 27, 721–727 (2004).

    Article  CAS  PubMed  Google Scholar 

  69. Aspireo reports data in further Phase 1b study: somatoprim demonstrates superior side effect profile over octreotide. Aspireo Pharmaceuticals [online], (2014).

  70. Lancranjan, L. et al. Sandostatin LAR®: pharmacokinetics, pharmacodynamics, efficacy, and tolerability in acromegalic patients. Metabolism 44, 18–26 (1995).

    Article  CAS  Google Scholar 

  71. Boyd, B. J., Whittaker, D. V., Khoo, S. M. & Davey, G. Lyotropic liquid crystalline phases formed from glycerate surfactants as sustained release drug delivery systems. Int. J. Pharm. 309, 218–226 (2006).

    Article  CAS  PubMed  Google Scholar 

  72. Rhee, Y. S. et al. Sustained-release delivery of octreotide from biodegradable polymeric microspheres. AAPS PharmSciTech 12, 1293–1301 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Stormann, S. & Schopohl, J. Emerging drugs for acromegaly. Expert Opin. Emerg. Drugs 19, 79–97 (2014).

    Article  CAS  PubMed  Google Scholar 

  74. US National Library of Medicine. Phase II study of subcutaneous injection depot of octreotide in patients with acromegaly and neuroendocrine tumours (NETs). ClinicalTrials.gov[online], (2015).

  75. Fricker, G. et al. Intestinal absorption of the octapeptide SMS 201-995 visualized by fluorescence derivatization. Gastroenterology 100, 1544–1552 (1991).

    Article  CAS  PubMed  Google Scholar 

  76. Fricker, G., Drewe, J., Vonderscher, J., Kissel, T. & Beglinger, C. Enteral absorption of octreotide. Br. J. Pharmacol. 105, 783–786 (1992).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Mehvar, R. & Shepard, T. L. Molecular-weight-dependent pharmacokinetics of fluorescein-labeled dextrans in rats. J. Pharm. Sci. 81, 908–912 (1992).

    Article  CAS  PubMed  Google Scholar 

  78. Bonazzi, M. & Cossart, P. Impenetrable barriers or entry portals? The role of cell–cell adhesion during infection. J. Cell Biol. 195, 349–358 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Berkes, J., Viswanathan, V. K., Savkovic, S. D. & Hecht, G. Intestinal epithelial responses to enteric pathogens: effects on the tight junction barrier, ion transport, and inflammation. Gut 52, 439–451 (2003).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Pijls, K. E., Jonkers, D. M., Elamin, E. E., Masclee, A. A. & Koek, G. H. Intestinal epithelial barrier function in liver cirrhosis: an extensive review of the literature. Liver Int. 33, 1457–1469 (2013).

    PubMed  Google Scholar 

  81. Turner, J. R. Intestinal mucosal barrier function in health and disease. Nat. Rev. Immunol. 9, 799–809 (2009).

    Article  CAS  PubMed  Google Scholar 

  82. Chanson, P. et al. Comparison of octreotide acetate LAR and lanreotide SR in patients with acromegaly. Clin. Endocrinol. (Oxf.) 53, 577–586 (2000).

    Article  CAS  Google Scholar 

  83. Fleseriu, M. Clinical efficacy and safety results for dose escalation of somatostatin receptor ligands in patients with acromegaly: a literature review. Pituitary 14, 184–193 (2011).

    Article  CAS  PubMed  Google Scholar 

  84. Strasburger, C. J. et al. Patient reported outcomes survey in acromegaly patients treated with parenteral somatostatin analogues. [abstract THR-484], Presented at the Endocrine Society's 97th Annual Meeting and Exposition (2015).

  85. Bonert, V. S. et al. Lipodystrophy in patients with acromegaly receiving pegvisomant. J. Clin. Endocrinol. Metab. 93, 3515–3518 (2008).

    Article  CAS  PubMed  Google Scholar 

  86. Neggers, S. J. et al. Long-term efficacy and safety of combined treatment of somatostatin analogs and pegvisomant in acromegaly. J. Clin. Endocrinol. Metab. 92, 4598–4601 (2007).

    Article  CAS  PubMed  Google Scholar 

  87. Neggers, S. J. et al. Long-term efficacy and safety of pegvisomant in combination with long-acting somatostatin analogs in acromegaly. J. Clin. Endocrinol. Metab. 99, 3644–3652 (2014).

    Article  CAS  PubMed  Google Scholar 

  88. Trainer, P. J., Ezzat, S., D'Souza, G. A., Layton, G. & Strasburger, C. J. A randomized, controlled, multicentre trial comparing pegvisomant alone with combination therapy of pegvisomant and long-acting octreotide in patients with acromegaly. Clin. Endocrinol. (Oxf.) 71, 549–557 (2009).

    Article  CAS  Google Scholar 

  89. ATL1103 successfully progresses towards Phase II clinical trial. Antisense.com [online], (2011).

Download references

Acknowledgements

The author is grateful to S. Berman for skilled assistance in manuscript preparation.

Author information

Authors and Affiliations

  1. Department of Medicine, Pituitary Center, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Room 2015, Los Angeles, 90048, California, USA

    Shlomo Melmed

Authors
  1. Shlomo Melmed
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shlomo Melmed.

Ethics declarations

Competing interests

S.M. serves as a scientific consultant for Chiasma and Isis Pharmaceuticals, as an educational consultant for Novartis and has received research grants from Ipsen and Pfizer.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Melmed, S. New therapeutic agents for acromegaly. Nat Rev Endocrinol 12, 90–98 (2016). https://doi.org/10.1038/nrendo.2015.196

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrendo.2015.196

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing