Investigational drugs for the treatment of acromegaly: new agents to transform therapy

References

• Colao A, Grasso LFS, Giustina A, et al. Acromegaly. Nat Rev Dis Primers. 2019 Mar 21;5(1):20. doi: 10.1038/s41572-019-0071-6
   PubMed Web of Science ®Google Scholar
• Colao A, Vandeva S, Pivonello R, et al. Could different treatment approaches in acromegaly influence life expectancy? A comparative study between Bulgaria and Campania (Italy). Eur J Endocrinol. 2014 Aug;171(2):263–273.
   PubMed Web of Science ®Google Scholar
• Giustina A, Barkhoudarian G, Beckers A, et al. Multidisciplinary management of acromegaly: a consensus. Rev Endocr Metab Disord. 2020 Dec;21(4):667–678.
   PubMed Web of Science ®Google Scholar
• Zamanipoor Najafabadi AH, van der Meulen M, Priego Zurita AL, et al. MTG6 pituitary of endo-ERN. Starting point for benchmarking outcomes and reporting of pituitary adenoma surgery within the European reference network on rare endocrine conditions (Endo-ERN): results from a meta-analysis and survey study. Endocr Connect. 2022 Dec 13;12(1):e220349. doi: 10.1530/EC-22-0349
   PubMed Web of Science ®Google Scholar
• Urwyler SA, Samperi I, Lithgow K, et al. Efficacy of cabergoline in non-irradiated patients with acromegaly: a multi-centre cohort study. Eur J Endocrinol. 2024 Jan;17:lvae003.
   Google Scholar
• Acromegaly Consensus Group, Giustina A, Chanson P, et al. Expert consensus document: a consensus on the medical treatment of acromegaly. Nat Rev Endocrinol. 2014 Apr;10(4):243–248.
   PubMed Web of Science ®Google Scholar
• Gadelha MR, Wildemberg LE, Bronstein MD, et al. Somatostatin receptor ligands in the treatment of acromegaly. Pituitary. 2017 Feb;20(1):100–108. doi: 10.1007/s11102-017-0791-0
   PubMed Web of Science ®Google Scholar
• Colao A, Auriemma RS, Pivonello R. The effects of somatostatin analogue therapy on pituitary tumor volume in patients with acromegaly. Pituitary. 2016 Apr;19(2):210–221. doi:10.1007/s11102-015-0677-y
   PubMed Web of Science ®Google Scholar
• Colao A, Auriemma RS, Lombardi G, et al. Resistance to somatostatin analogs in acromegaly. Endocr Rev. 2011 Apr;32(2):247–271. doi: 10.1210/er.2010-0002
   PubMed Web of Science ®Google Scholar
• Maione L, Chanson P. National acromegaly registries. Best Pract ResClin Endocrinol Metab. 2019 Apr;33(2):101264. doi:10.1016/j.beem.2019.02.001
   PubMed Web of Science ®Google Scholar
• Pasireotide C2305 Study GroupColao A, Bronstein MD, Freda P, et al. Pasireotide versus octreotide in acromegaly: a head-to-head superiority study. J Clin Endocrinol Metab. 2014 Mar;99(3):791–799. doi: 10.1210/jc.2013-2480
   PubMed Web of Science ®Google Scholar
• Pasireotide C2402 Study Group, Gadelha MR, Bronstein MD, 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. 2014 Nov;2(11):875–884. doi: 10.1016/S2213-8587(14)70169-X
   PubMed Web of Science ®Google Scholar
• Leonart LP, Tonin FS, Ferreira VL, et al. Effectiveness and safety of pegvisomant: a systematic review and meta-analysis of observational longitudinal studies. Endocrine. 2019 Jan;63(1):18–26.
   PubMed Web of Science ®Google Scholar
• Pirchio R, Auriemma RS, Montini ME, et al. Control of acromegaly in more than 90% of patients after 10 years of pegvisomant therapy: an European referral centre real-life experience. J Endocrinol Invest. 2023 May;46(5):1027–1038. doi: 10.1007/s40618-022-01980-7
   PubMed Web of Science ®Google Scholar
• Kizilgul M, Duger H, Nasiroglu NI, et al. Efficacy of cabergoline add-on therapy in patients with acromegaly resistance to somatostatin analogs treatment and the review of literature. Arch Endocrinol Metab. 2022 May 25;66(3):278–285. doi: 10.20945/2359-3997000000481
   PubMed Web of Science ®Google Scholar
• Mercado M, Abreu C, Vergara-López A, et al. Surgical and pharmacological outcomes in acromegaly: real-life data from the Mexican acromegaly registry. J Clin Endocrinol Metab. 2020 Dec 1;105(12):dgaa664. doi: 10.1210/clinem/dgaa664
   PubMed Web of Science ®Google Scholar
• Yamaguchi H, Shimatsu A, Okayama A, et al. Long-term safety and treatment outcomes of pegvisomant in Japanese patients with acromegaly: results from the post-marketing surveillance. Endocr J. 2020 Feb 28;67(2):201–210. doi: 10.1507/endocrj.EJ19-0266
   PubMed Web of Science ®Google Scholar
• Basavilbaso NXG, Ballarino MC, Bruera D, et al. Pegvisomant in acromegaly: a multicenter real-life study in Argentina. Arch Endocrinol Metab. 2019 Aug 22;63(4):320–327. doi: 10.20945/2359-3997000000160
   PubMed Web of Science ®Google Scholar
• Colao A, Zgliczyński W, Komorowski J, et al. Efficacy and safety of high-dose long-acting repeatable octreotide as monotherapy or in combination with pegvisomant or cabergoline in patients with acromegaly not adequately controlled by conventional regimens: results of an open-label, multicentre study. Endokrynol Pol. 2019;70(4):305–312. doi: 10.5603/EP.a2019.0023
   PubMed Web of Science ®Google Scholar
• Shimon I, Adnan Z, Gorshtein A, et al. Efficacy and safety of long-acting pasireotide in patients with somatostatin-resistant acromegaly: a multicenter study. Endocrine. 2018 Nov;62(2):448–455.
   PubMed Web of Science ®Google Scholar
• Casagrande A, Bronstein MD, Jallad RS, et al. Remission of acromegaly after treatment withdrawal in patients controlled by cabergoline alone or in combination with octreotide: results from a multicenter study. J Endocrinol Invest May. 2017;40(5):523–528. doi: 10.1007/s40618-016-0595-5
   PubMed Web of Science ®Google Scholar
• Puig-Domingo M, Soto A, Venegas E, et al. ACROCOMB study group. Use of lanreotide in combination with cabergoline or pegvisomant in patients with acromegaly in the clinical practice: The ACROCOMB study. Endocrinol Nutr. 2016 Oct;63(8):397–408.
   PubMedGoogle Scholar
• Valea A, Ghervan C, Carsote M, et al. Effects of combination therapy: somatostatin analogues and dopamine agonists on GH and IGF1 levels in acromegaly. Clujul Med. 2015;88(3):310–313. doi: 10.15386/cjmed-435
   PubMedGoogle Scholar
• Vandeva S, Elenkova A, Natchev E, et al. Treatment outcome results from the Bulgarian acromegaly database: adjuvant dopamine agonist therapy is efficient in less than one fifth of non-irradiated patients. Exp Clin Endocrinol Diabetes. 2015 Jan;123(1):66–71.
   PubMed Web of Science ®Google Scholar
• Bernabeu I, Alvarez-Escolá C, Paniagua AE, et al. Pegvisomant and cabergoline combination therapy in acromegaly. Pituitary. 2013 Mar;16(1):101–108. doi: 10.1007/s11102-012-0382-z
   PubMed Web of Science ®Google Scholar
• Suda K, Inoshita N, Iguchi G, et al. Efficacy of combined octreotide and cabergoline treatment in patients with acromegaly: a retrospective clinical study and review of the literature. Endocr J. 2013;60(4):507–515. doi: 10.1507/endocrj.EJ12-0272
   PubMed Web of Science ®Google Scholar
• Higham CE, Atkinson AB, Aylwin S, et al. Effective combination treatment with cabergoline and low-dose pegvisomant in active acromegaly: a prospective clinical trial. J Clin Endocrinol Metab. 2012 Apr;97(4):1187–1193. doi: 10.1210/jc.2011-2603
   PubMed Web of Science ®Google Scholar
• Mattar P, Alves Martins MR, Abucham J. Short- and long-term efficacy of combined cabergoline and octreotide treatment in controlling igf-I levels in acromegaly. Neuroendocrinology. 2010;92(2):120–127. doi:10.1159/000317314
   PubMed Web of Science ®Google Scholar
• Jallad RS, Bronstein MD. Optimizing medical therapy of acromegaly: beneficial effects of cabergoline in patients uncontrolled with long-acting release octreotide. Neuroendocrinology. 2009;90(1):82–92. doi:10.1159/000218323
   PubMed Web of Science ®Google Scholar
• Gatta B, Hau DH, Catargi B, et al. Re-evaluation of the efficacy of the association of cabergoline to somatostatin analogues in acromegalic patients. Clin Endocrinol (Oxf). 2005 Oct;63(4):477–478.
   PubMed Web of Science ®Google Scholar
• Selvarajah D, Webster J, Ross R, et al. Effectiveness of adding dopamine agonist therapy to long-acting somatostatin analogues in the management of acromegaly. Eur J Endocrinol. 2005 Apr;152(4):569–574. doi: 10.1530/eje.1.01888
   PubMed Web of Science ®Google Scholar
• Cozzi R, Attanasio R, Lodrini S, et al. Cabergoline addition to depot somatostatin analogues in resistant acromegalic patients: efficacy and lack of predictive value of prolactin status. Clin Endocrinol (Oxf). 2004 Aug;61(2):209–215.
   PubMed Web of Science ®Google Scholar
• Chiloiro S, Giampietro A, Visconti F, et al. Glucose metabolism outcomes in acromegaly patients on treatment with pasireotide-LAR or pasireotide-LAR plus Pegvisomant. Endocrine. 2021 Sep;73(3):658–666.
   PubMed Web of Science ®Google Scholar
• Kuhn E, Caron P, Delemer B, et al. Pegvisomant in combination or pegvisomant alone after failure of somatostatin analogs in acromegaly patients: an observational French ACROSTUDY cohort study. Endocrine. 2021 Jan;71(1):158–167.
   PubMed Web of Science ®Google Scholar
• Ma L, Luo D, Yang T, et al. Combined therapy of somatostatin analogues with pegvisomant for the treatment of acromegaly: a meta-analysis of prospective studies. BMC Endocr Disord. 2020 Aug 18;20(1):126. doi: 10.1186/s12902-020-0545-2
   PubMed Web of Science ®Google Scholar
• Chiloiro S, Bima C, Tartaglione T, et al. Pasireotide and pegvisomant combination treatment in acromegaly resistant to second-line therapies: a longitudinal study. J Clin Endocrinol Metab. 2019 Nov 1;104(11):5478–5482. doi: 10.1210/jc.2019-00825
   PubMed Web of Science ®Google Scholar
• Feola T, Cozzolino A, Simonelli I, et al. Pegvisomant improves glucose metabolism in acromegaly: a meta-analysis of prospective interventional studies. J Clin Endocrinol Metab. 2019 Jul 1;104(7):2892–2902. doi: 10.1210/jc.2018-02281
   PubMed Web of Science ®Google Scholar
• Strasburger CJ, Mattsson A, Wilton P, et al. Increasing frequency of combination medical therapy in the treatment of acromegaly with the GH receptor antagonist pegvisomant. Eur J Endocrinol Apr. 2018;178(4):321–329. doi: 10.1530/EJE-17-0996
   PubMed Web of Science ®Google Scholar
• Muhammad A, van der Lely AJ, Delhanty PJD, et al. Efficacy and safety of switching to pasireotide in patients with acromegaly controlled with pegvisomant and first-generation somatostatin analogues (PAPE Study). J Clin Endocrinol Metab. 2018 Feb 1;103(2):586–595. doi: 10.1210/jc.2017-02017
   PubMed Web of Science ®Google Scholar
• Auriemma RS, Grasso LF, Galdiero M, et al. Effects of long-term combined treatment with somatostatin analogues and pegvisomant on cardiac structure and performance in acromegaly. Endocrine Mar. 2017;55(3):872–884. doi: 10.1007/s12020-016-0995-5
   PubMed Web of Science ®Google Scholar
• Neggers SJ, Franck SE, de Rooij FW, et al. Long-term efficacy and safety of pegvisomant in combination with long-acting somatostatin analogs in acromegaly. J Clin Endocrinol Metab. 2014 Oct;99(10):3644–3652.
   PubMed Web of Science ®Google Scholar
• Bianchi A, Valentini F, Iuorio R, et al. Long-term treatment of somatostatin analog-refractory growth hormone-secreting pituitary tumors with pegvisomant alone or combined with long-acting somatostatin analogs: a retrospective analysis of clinical practice and outcomes. J Exp Clin Cancer Res. 2013 Jun 21;32(1):40. doi: 10.1186/1756-9966-32-40
   PubMedGoogle Scholar
• Neggers SJ, de Herder WW, Feelders RA, et al. Conversion of daily pegvisomant to weekly pegvisomant combined with long-acting somatostatin analogs, in controlled acromegaly patients. Pituitary. 2011 Sep;14(3):253–258.
   PubMed Web of Science ®Google Scholar
• Madsen M, Poulsen PL, Orskov H, et al. Cotreatment with pegvisomant and a somatostatin analog (SA) in SA-responsive acromegalic patients. J Clin Endocrinol Metab. 2011 Aug;96(8):2405–2413.
   PubMed Web of Science ®Google Scholar
• van der Lely AJ, Bernabeu I, Cap J, et al. Coadministration of lanreotide autogel and pegvisomant normalizes IGF1 levels and is well tolerated in patients with acromegaly partially controlled by somatostatin analogs alone. Eur J Endocrinol Mar. 2011;164(3):325–333. doi: 10.1530/EJE-10-0867
   PubMed Web of Science ®Google Scholar
• Neggers SJ, de Herder WW, Janssen JA, et al. Combined treatment for acromegaly with long-acting somatostatin analogs and pegvisomant: long-term safety for up to 4.5 years (median 2.2 years) of follow-up in 86 patients. Eur J Endocrinol. 2009 Apr;160(4):529–533. doi: 10.1530/EJE-08-0843
   PubMed Web of Science ®Google Scholar
• Jawiarczyk A, Kałuzny M, Bolanowski M, et al. Additional metabolic effects of adding GH receptor antagonist to long-acting somatostatin analog in patients with active acromegaly. Neuro Endocrinol Lett. 2008 Aug;29(4):571–576.
   PubMed Web of Science ®Google Scholar
• De Marinis L, Bianchi A, Fusco A, et al. Long-term effects of the combination of pegvisomant with somatostatin analogs (SSA) on glucose homeostasis in non-diabetic patients with active acromegaly partially resistant to SSA. Pituitary. 2007;10(3):227–232. doi: 10.1007/s11102-007-0037-7
   PubMed Web of Science ®Google Scholar
• Katznelson L, ER L Jr, Melmed S, et al. Endocrine Society. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014 Nov;99(11):3933–3951.
   PubMed Web of Science ®Google Scholar
• Pivonello R, Auriemma RS, Grasso LF, et al. Complications of acromegaly: cardiovascular, respiratory and metabolic comorbidities. Pituitary. 2017 Feb;20(1):46–62. doi: 10.1007/s11102-017-0797-7
   PubMed Web of Science ®Google Scholar
• Colao A, Grasso LFS, Di Cera M, et al. Association between biochemical control and comorbidities in patients with acromegaly: an Italian longitudinal retrospective chart review study. J Endocrinol Invest. 2020 Apr;43(4):529–538. doi: 10.1007/s40618-019-01138-y
   PubMed Web of Science ®Google Scholar
• Gadelha MR, Kasuki L, Lim DST, et al. Systemic complications of acromegaly and the impact of the current treatment landscape: an update. Endocr Rev. 2019 Feb 1;40(1):268–332. doi: 10.1210/er.2018-00115
   PubMed Web of Science ®Google Scholar
• Pivonello R, Auriemma RS, Delli Veneri A, et al. Global psychological assessment with the evaluation of life and sleep quality and sexual and cognitive function in a large number of patients with acromegaly: a cross-sectional study. Eur J Endocrinol. 2022 Dec 13;187(6):823–845. doi: 10.1530/EJE-22-0263
   PubMed Web of Science ®Google Scholar
• Samson SL, Nachtigall LB, Fleseriu M, et al. Maintenance of acromegaly control in patients switching from injectable somatostatin receptor ligands to oral octreotide. J Clin Endocrinol Metab. 2020 Oct 1;105(10):e3785–97. doi: 10.1210/clinem/dgaa526
   PubMed Web of Science ®Google Scholar
• Tuvia S, Atsmon J, Teichman SL, et al. Oral octreotide absorption in human subjects: comparable pharmacokinetics to parenteral octreotide and effective growth hormone suppression. J Clin Endocrinol Metab. 2012 Jul;97(7):2362–2369.
   PubMed Web of Science ®Google Scholar
• Melmed S, Popovic V, Bidlingmaier M, et al. Safety and efficacy of oral octreotide in acromegaly: results of a multicenter phase III trial. J Clin Endocrinol Metab Apr. 2015;100(4):1699–1708. doi: 10.1210/jc.2014-4113
   PubMed Web of Science ®Google Scholar
• Fleseriu M, Molitch M, Dreval A, et al. MPOWERED trial open-label extension: long-term efficacy and safety data for oral octreotide capsules in acromegaly. J Clin Endocrinol Metab. 2023 Jun;16:dgad365. doi: 10.1530/endoabs.81.OC4.3
   Google Scholar
• Fleseriu M, Biller BMK, Freda PU, et al. A Pituitary Society update to acromegaly management guidelines. Pituitary. 2021 Feb;24(1):1–13.
   PubMed Web of Science ®Google Scholar
• Schöfl C, Grussendorf M, Honegger J, et al. Failure to achieve disease control in acromegaly: cause analysis by a registry-based survey. Eur J Endocrinol. 2015 Apr;172(4):351–356. doi: 10.1530/EJE-14-0844
   PubMed Web of Science ®Google Scholar
• Salvatori R, Woodmansee WW, Molitch M, et al. 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 Feb. 2014;17(1):13–21. doi: 10.1007/s11102-012-0460-2
   PubMed Web of Science ®Google Scholar
• O’Toole D, Kunz PL, Webb SM, et al. PRESTO 2: an international survey to evaluate patients’ injection experiences with the latest devices/formulations of long-acting somatostatin analog therapies for neuroendocrine tumors or acromegaly. Adv Ther. 2023 Feb;40(2):671–690. doi: 10.1007/s12325-022-02360-6
   PubMed Web of Science ®Google Scholar
• Grasso LF, Auriemma RS, Pivonello R, et al. Adverse events associated with somatostatin analogs in acromegaly. Expert Opin Drug Saf. 2015 Aug;14(8):1213–1226.
   PubMed Web of Science ®Google Scholar
• Cocchiara F, Campana C, Nista F, et al. Evaluation of acromegaly treatment direct costs with respect to biochemical control and follow-up length. Pituitary. 2022 Apr;25(2):246–257. doi: 10.1007/s11102-021-01193-w
   PubMed Web of Science ®Google Scholar
• Lesén E, Granfeldt D, Houchard A, et al. Comorbidities, treatment patterns and cost-of-illness of acromegaly in Sweden: a register-linkage population-based study. Eur J Endocrinol Feb. 2017;176(2):203–212. doi: 10.1530/EJE-16-0623
   PubMed Web of Science ®Google Scholar
• Zhao J, Wang S, Markison S, et al. Discovery of paltusotine (CRN00808), a potent, selective, and orally bioavailable non-peptide SST2 agonist. ACS Med Chem Lett. 2022 Dec 10;14(1):66–74. doi: 10.1021/acsmedchemlett.2c00431
   PubMed Web of Science ®Google Scholar
• Madan A, Luo R, Ferrara-Cook C, et al. Absolute oral bioavailability and absorption, metabolism, excretion of [14C]-labeled paltusotine (CRN00808), an orally bioavailable, nonpeptide, selective, somatostatin receptor 2 (sst2) biased agonist for the treatment of acromegaly. Endocrine Abstracts. 2020;70:AEP627. doi: 10.1530/endoabs.70.AEP627
   Google Scholar
• Madan A, Markison S, Betz SF, et al. Paltusotine, a novel oral once-daily nonpeptide SST2 receptor agonist, suppresses GH and IGF-1 in healthy volunteers. Pituitary. 2022 Apr;25(2):328–339. doi:10.1007/s11102-021-01201-z
   PubMed Web of Science ®Google Scholar
• Gadelha MR, Gordon MB, Doknic M, et al. ACROBAT edge: safety and efficacy of switching injected SRLs to oral paltusotine in patients with acromegaly. J Clin Endocrinol Metab. 2023 Apr 13;108(5):e148–e159. doi: 10.1210/clinem/dgac643
   PubMed Web of Science ®Google Scholar
• [cited 2024 Feb 29]. Available from: https://clinicaltrials.gov/study/NCT03792555?term=acrobat%20evolve&rank=1
   Google Scholar
• [cited 2024 Feb 29]. Available from: https://clinicaltrials.gov/study/NCT04261712?term=acrobat%20advance&rank=1
   Google Scholar
• Randeva H, Gadelha MR, Gordon MB, et al. Acrobat advance: progress report on a study of long-term safety and efficacy of paltusotine for the treatment of acromegaly. Endocrino Abstracts. 2021;77:80. doi: 10.1530/endoabs.77.P80
   Google Scholar
• Gadelha MR, Randeva H, Gordon MB, et al. Oral, oncedaily, paltusotine (non-peptide selective somatostatin receptor subtype 2agonist) therapy in patients with acromegaly is associated with long-term biochemical and symptom control and is preferred over injectable somatostatin receptor Annual Meeting. 2023. OR01–01.
   Google Scholar
• Lou R, Burke G, Mui C, et al. Pharmacokinetics and safety of an improved oral formulation of paltusotine, a selective, non-peptide somatostatin receptor 2 (SST2) agonist for the treatment of acromegaly. Endocrine Society. 2021 Mar 20;2021.
   Google Scholar
• Available from: https://clinicaltrials.gov/study/NCT04837040?cond=acromegaly&term=paltusotine&rank=4
   Google Scholar
• https://crinetics.com/crinetics-paltusotine-achieved-primary-and-secondary-endpoints-in-phase-3-pathfndr-1-acromegaly-study/accessed on 20 feb 2024
   Google Scholar
• [cited 2024 feb 29]. Available from: https://clinicaltrials.gov/study/NCT05192382
   Google Scholar
• Kaviya A, O’Reilly T, Batonga J, et al. SAT-430 a phase 1 study in healthy volunteers to assess the safety, tolerability, and pharmacokinetics of ONO-5788: a novel oral small molecule somatostatin receptor type-2 agonist. J Endocr Soc. 2019 Apr;3(Supplement_1):SAT–430.
   Google Scholar
• Zhou C. PhD and others, MON-459 ONO-5788, a novel oral small molecule somatostatin receptor type-2 (SST2) agonist, attenuates gh hypersecretion in human gh-secreting, pituitary adenoma-derived cells. J Endocr Soc. 2019 Apr;3(Supplement_1):MON–459. doi: 10.1210/js.2019-MON-459
   Google Scholar
• Komagata T. MON-464 Non-Clinical Profiling of ONO-5788, a Novel Oral Small Molecule Somatostatin Receptor Type-2 (SST2) Agonist, to Support Studies in Humans. J Endocr Soc. 2019;3.
   Google Scholar
• Available from: https://clinicaltrials.gov/study/NCT03571594
   Google Scholar
• Kaviya A, O’Reilly T, Batonga J, et al. SAT-430 a phase 1 study in healthy volunteers to assess the safety, tolerability, and pharmacokinetics of ono-5788: a novel oral small molecule somatostatin receptor type-2 agonist. J Endocr Soc. 2019 Apr;3(Supplement_1):SAT–430. doi: 10.1210/js.2019-SAT-430
   Google Scholar
• [cited 2024 feb 27]. Available from: https://clinicaltrials.gov/study/NCT03849872?intr=NCT03849872&rank=1
   Google Scholar
• Tanaka H, Komagata T, Nishio T, et al. MON-477 octreotide and ono-st-468, a novel and potent somatostatin receptor type-2 (sst2) agonist, suppress gh hypersecretion in the monkey. J Endocr Soc. 2019 Apr 30;3(Suppl 1):MON–477. doi: 10.1210/js.2019-MON-477
   Google Scholar
• Streuli J, Harris AG, Cottiny C, et al. Cellular effects of AP102, a somatostatin analog with balanced affinities for the hSSTR2 and hSSTR5 receptors. Neuropeptides Apr. 2018;68:84–89. doi: 10.1016/j.npep.2018.02.005
   PubMed Web of Science ®Google Scholar
• Eugster PJ, Boyle CN, Prod’hom S, et al. Sensitive quantification of the somatostatin analog AP102 in plasma by ultra-high pressure liquid chromatography-tandem mass spectrometry and application to a pharmacokinetic study in rats. Drug Test Anal. 2018 Sep;10(9):1448–1457.
   PubMed Web of Science ®Google Scholar
• [cited 2024 Feb 26]. Available from: https://www.glytech-inc.com/pipeline/gt-02037/
   Google Scholar
• Tiberg F, Roberts J, Cervin C, et al. Octreotide s.c. depot provides sustained octreotide bioavailability and similar IGF-1 suppression to octreotide LAR in healthy volunteers. Br J Clin Pharmacol. 2015 Sep;80(3):460–72.
   Google Scholar
• [cited 2024 Feb 26]. Available from: https://clinicaltrials.gov/study/NCT03548415?cond=acromegaly&term=ISIS%20766720&rank=1
   Google Scholar
• [cited 2024 Feb 26. Available from: https://ir.ionispharma.com/static-files/bbfabc7a-ccf2-44bb-a72d-6edba88a17e4
   Google Scholar
• [cited 2024 Feb 26]. Available from: https://clinicaltrials.gov/study/NCT04522180?cond=acromegaly&term=ISIS%20766720&rank=2
   Google Scholar
• Bhanot S, Fleseriu M, Geary R, et al. OR27-4 placebo-controlled and open-label extension study of a novel hepatic-targeted antisense cimdelirsen (IONIS-GHR-LRX) under investigation in acromegaly patients. J Endocr Soc. 2022 Nov 1;6(Suppl 1):A526. doi: 10.1210/jendso/bvac150.1095
   Google Scholar
• [cited 2024 Feb 29]. Available from: https://www.clinicaltrials.gov/study/NCT03967249
   Google Scholar
• Pavel M, Borson-Chazot F, Cailleux A, et al. Octreotide SC depot in patients with acromegaly and functioning neuroendocrine tumors: a phase 2, multicenter study. Cancer Chemother Pharmacol Feb. 2019;83(2):375–385. doi: 10.1007/s00280-018-3734-1
   PubMed Web of Science ®Google Scholar
• [cited 2024 Feb 27. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT04076462
   Google Scholar
• [cited 2024 Feb 27]. Available from: https://clinicaltrials.gov/study/NCT04125836
   Google Scholar
• Neggers S, Badiu C, Biagetti B, et al. Pharmacological and safety profile of a prolonged-release lanreotide formulation in acromegaly. Expert Rev Clin Pharmacol. 2021 Dec;14(12):1551–1560.
   PubMed Web of Science ®Google Scholar
• Sahakian N, Castinetti F, Brue T, et al. Current and emerging medical therapies in pituitary tumors. J Clin Med. 2022 Feb 12;11(4):955. doi:10.3390/jcm11040955. PMID: 35207228; PMCID: PMC8877616.
   PubMed Web of Science ®Google Scholar
• [cited 2024 Feb 26]. Availble from: https://clinicaltrials.gov/study/NCT03031535?intr=dp-1038&rank=1
   Google Scholar
• [cited 2024 Feb 26. Available from: https://kuleuvencongres.be/laiconference/documents/bamsey-katherine-mtd201-new-generation-treatment.pdf
   Google Scholar
• [cited 2024 Feb 26. Available from: https://www.biospace.com/article/releases/glide-technologies-announces-successful-clinical-proof-of-concept-study-with-its-novel-octreotide-solid-dose-formulation-delivered-via-sdi-/
   Google Scholar
• [cited 2024 Feb 26]. Available from: https://www.cbinsights.com/company/dauntless-2
   Google Scholar
• [cited 2024 Feb 27. Available from: https://www.annualreports.com/HostedData/AnnualReportArchive/a/NASDAQ_AQST_2020.pdf
   Google Scholar
• [cited 2024 Feb 27]. Available from: https://adisinsight.springer.com/trials/700301814
   Google Scholar
• Labadzhyan A, Melmed S. Molecular targets in acromegaly. Front Endocrinol. 2022 Dec 5;13:1068061. doi: 10.3389/fendo.2022.1068061
   PubMed Web of Science ®Google Scholar
• Ben-Shlomo A, Cooper O. Role of tyrosine kinase inhibitors in the treatment of pituitary tumours: from bench to bedside. Curr Opin Endocrinol Diabetes Obes. 2017 Aug;24(4):301–305. doi: 10.1097/MED.0000000000000344
   PubMedGoogle Scholar
• Cooper O, Bonert VS, Rudnick J, et al. EGFR/ErbB2-targeting lapatinib therapy for aggressive prolactinomas. J Clin Endocrinol Metab. 2021 Jan 23;106(2):e917–e925. doi: 10.1210/clinem/dgaa805
   PubMed Web of Science ®Google Scholar
• Auriemma RS, Pirchio R, Pivonello C, et al. Approach to the patient with prolactinoma. J Clin Endocrinol Metab. 2023 Aug 18;108(9):2400–2423. doi: 10.1210/clinem/dgad174
   PubMed Web of Science ®Google Scholar
• Fougner SL, Lekva T, Borota OC, et al. The expression of E-cadherin in somatotroph pituitary adenomas is related to tumor size, invasiveness, and somatostatin analog response. J Clin Endocrinol Metab. 2010 May;95(5):2334–2342.
   PubMed Web of Science ®Google Scholar
• Nista F, Corica G, Castelletti L, et al. Clinical and radiological predictors of biochemical response to first-line treatment with somatostatin receptor ligands in acromegaly: a real-life perspective. Front Endocrinol. 2021 May 7;12:677919.
   PubMed Web of Science ®Google Scholar
• Ilie MD, Tabarin A, Vasiljevic A, et al. Predictive factors of somatostatin receptor ligand response in acromegaly-a prospective study. J Clin Endocrinol Metab. 2022 Nov 23;107(11):2982–2991.
   PubMed Web of Science ®Google Scholar
• Marques-Pamies M, Gil J, Jordà M, et al. Predictors of response to treatment with first-generation somatostatin receptor ligands in patients with acromegaly. Arch Med Res. 2023 Dec;54(8):102924.
   PubMed Web of Science ®Google Scholar
• Durán-Prado M, Saveanu A, Luque RM, et al. A potential inhibitory role for the new truncated variant of somatostatin receptor 5, sst5TMD4, in pituitary adenomas poorly responsive to somatostatin analogs. J Clin Endocrinol Metab. 2010 May;95(5):2497–2502.
   PubMed Web of Science ®Google Scholar