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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EAcromegaly is caused by an overproduction of growth hormone, and subsequently, insulin-like growth factor-I. ALT1103 is second-generation drug that reduces expression of the growth hormone receptor. In a phase 2 trial, patients with acromegaly who received 400 mg of ALT1103 showed a significant reduction in insulin-like growth factor-I at 14 weeks.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Eacromegaly\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EATL1103\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Einsulin-like growth factor-I\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Epituitary gland disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eendocrinology, diabetes \u0026amp; metabolism clinical trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003E2012-003147-30\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003EAcromegaly is a chronic disorder resulting from excessive secretion of growth hormone, with a resulting increase in the production of the hormone known as insulinlike growth factor 1 (IGF-1). ATL1103 is a second-generation antisense drug designed to silence growth hormone receptor expression, thereby reducing levels of IGF-1 in the blood. It is currently under investigation as a potential treatment for diseases associated with excessive growth hormone action, such as acromegaly [St\u00f6rmann S, Schopohl J. \u003Cem\u003EExpert Opin Emerg Drugs\u003C\/em\u003E. 2014].\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EPeter J. Trainer, MD, The Christie National Health Service Foundation Trust, Manchester, United Kingdom, reported primary efficacy results from the phase 2 clinical trial of ATL1103 in patients with acromegaly [2012-003147-30]. The ATL1103 phase 2 trial was a randomized, open-label, multicenter, parallel group study of the safety, tolerability, pharmacokinetics, and efficacy of 2 subcutaneous dosing regimens of ATL1103 in 26 adult patients in the United Kingdom, France, Spain, and Australia. Patients were required to have active acromegaly, defined as an IGF-1 level\u2005\u0026gt;\u2005130% of the upper limits of normal. In addition, patients had to undergo a washout from long-acting somatostatin agonists (4 months) and dopamine agonists (6-8 weeks). Patients were excluded if they had a tumor within 3 mm of the optic chiasm or had undergone pituitary surgery within 3 months or radiotherapy within 1 year.\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EOver a period of 13 weeks, patients were randomized to 2 groups. One group (n\u2005=\u200513) received the injection of 200 mg 3 times in the first week and 200 mg once weekly thereafter; the second group (n\u2005=\u200513) received 200 mg 3 times in the first week and 200 mg twice weekly thereafter. The primary end point was the percent change in IGF-1 at week 14. Pharmacokinetics and safety were also measured. At baseline, patients in the 200 mg once weekly group were younger (mean age, 48\u2005\u00b1\u200514 vs 53\u2005\u00b1\u200517) and had greater weight (97\u2005\u00b1\u200520 vs 85\u2005\u00b1\u200525) than those in the 200 mg twice weekly group. However, both groups had a similar number of male patients (5 vs 6), patients who had prior radiotherapy (5 vs 6), and those who had prior surgery (13 vs 12).\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EOnly patients who received ATL1103 200 mg twice weekly showed a statistically significant reduction in IGF-1 levels at week 14 compared with baseline. Specifically, in the 200 mg twice weekly group, mean IGF-1 levels reduced by 26% from about 600 ng\/mL at baseline to nearly 400 ng\/mL at week 14 (\u003Cem\u003EP\u003C\/em\u003E\u2005\u0026lt;\u2005.0001), whereas in the 200 mg once weekly group, mean IGF-1 levels were about 500 ng\/mL at baseline, with a nonsignificant reduction at week 14. IGF-1 levels normalized in 1 patient in both groups at week 14. Mathematical modeling of the dose curve for the higher dose of ATL1103 suggests that the maximum reduction of IGF-1 would be seen at 17 or 21 weeks if the patients had been treated for that long.\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EThere were no significant changes in 2 secondary outcomes among patients on either dose, including signs and symptoms and the global Acromegaly Quality of Life score. Patient ring size was reduced significantly in the higher dose group (\u003Cem\u003EP\u003C\/em\u003E\u2005=\u2005.01).\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EThe 2 most frequent treatment-emergent events included injection site reactions and headache. One patient in each group withdrew from the study and there were 4 serious adverse events, none of which were thought to be drug related. No patient reported flulike symptoms, which are a recognized side effect in drugs of this class.\u003C\/p\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EProf Trainer concluded that for many patients with acromegaly, a larger dose of ATL1103 taken over a longer period of time will likely be well tolerated and able to produce improved disease control.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2015 SAGE Publications\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/15\/4\/14.2.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzl66q\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}