BOSTON--(BUSINESS WIRE)--Ironwood Pharmaceuticals, Inc. (Nasdaq: IRWD), a GI-focused healthcare company, today announced positive topline results from its pivotal Phase III STARS trial, which evaluated the efficacy and safety of once-weekly subcutaneous apraglutide in reducing parenteral support (PS) dependency in adult patients with short bowel syndrome with intestinal failure (SBS-IF).

波士顿-（商业新闻）-Ironwood Pharmaceuticals，Inc.（纳斯达克：IRWD），一家专注于胃肠道的医疗保健公司，今天宣布了其关键的III期STARS试验的阳性结果，该试验评估了每周一次皮下注射阿普鲁肽在减少成人短肠综合征伴肠衰竭（SBS-IF）患者肠外支持（PS）依赖性方面的疗效和安全性。

SBS-IF, a rare and severe organ failure condition in which patients are dependent on PS, affects an estimated 18,000 adult patients in the U.S., Europe, and Japan. Based on these results, Ironwood plans to submit a new drug application (NDA) and other regulatory filings for apraglutide for use in adult patients with SBS who are dependent on PS..

SBS-IF是一种罕见且严重的器官衰竭疾病，患者依赖PS，在美国，欧洲和日本估计有18000名成年患者受到影响。基于这些结果，Ironwood计划提交一份新药申请（NDA）和其他监管文件，用于依赖PS的成年SBS患者。

The global, multicenter, double-blind, randomized, placebo-controlled trial evaluated the efficacy and safety of weekly subcutaneous injections of apraglutide in adult patients with SBS-IF. The trial met its primary endpoint of relative change from baseline in actual weekly PS volume at week 24, comparing apraglutide versus placebo (-25.5% vs.-12.5%; p=0.001)..

这项全球性、多中心、双盲、随机、安慰剂对照试验评估了每周皮下注射阿普拉鲁肽治疗SBS-IF成年患者的疗效和安全性。该试验达到了主要终点，即在第24周时，阿普拉鲁肽与安慰剂相比，每周实际PS量与基线相比有相对变化（-25.5% vs.-12.5%; p=0.001）。

“Reducing dependency on parenteral support and easing treatment burden are important goals for every patient with SBS-IF,” said Kishore R Iyer, MBBS, FRCS (Eng), FACS, Director of Adult and Pediatric Intestine Rehabilitation & Transplantation at The Mount Sinai Hospital in New York, Coordinating Principal Investigator of the trial, paid scientific advisor to Ironwood and chair of the scientific steering committee for the STARS Trial.

纽约西奈山医院成人和儿科肠道康复与移植主任、该试验的主要协调人、MBBS、FRCS（Eng）、FACS的Kishore R Iyer说：“减少对肠外支持的依赖和减轻治疗负担是每位SBS-IF患者的重要目标，支付给Ironwood的科学顾问和STARS试验科学指导委员会主席。

“The STARS topline results are significant as this is the first successful Phase III placebo-controlled study in SBS-IF patients with a GLP-2 analog with once-weekly dosing.”.

“STARS topline结果很重要，因为这是SBS-IF患者中第一个成功的III期安慰剂对照研究，该研究使用GLP-2类似物，每周给药一次。”

In addition, there were four key secondary endpoints evaluated in statistical hierarchy. Apraglutide demonstrated statistical significance for the first two key secondary endpoints, with more patients in the combined population achieving at least one day/week off PS relative to baseline at week 24 versus placebo (43.0% vs.27.5%; p=0.040) and more patients treated with apraglutide versus placebo demonstrating improvement in relative change from baseline in actual weekly PS volume at week 24 in the stoma population (-25.6% vs. -7.8%; p<0.001). The third and fourth key secondary endpoints were specific to colon-in-continuity patients in assessing at least one day/week off PS versus baseline and reaching enteral autonomy at week 48, both of which were not achieved.

此外，还对四个关键次要终点进行了分层统计评估。阿普拉鲁肽在前两个关键次要终点上具有统计学意义，与安慰剂相比，在第24周时，合并人群中有更多患者实现了相对于基线至少减少一天/周的PS（43.0% vs. 27.5%；p=0.040），在造口人群中，与安慰剂相比，在第24周时，有更多接受阿普拉鲁肽治疗的患者在每周实际PS量与基线的相对变化上有所改善（-25.6% vs. -7.8%；p<0.001）。第三和第四个关键次要终点是针对结肠不连续患者的，评估至少有一天/周不再使用PS与基线相比，以及在第48周达到肠内自主，这两个终点均未达到。

Apraglutide was numerically favorable but not statistically significant relative to placebo for improving days off PS (51.8% versus 44.4%) and reaching enteral autonomy in seven out of 56 (12.5%) patients versus two out of 27 (7.4%) patients on placebo..

阿帕鲁肽在数值上是有利的，但相对于安慰剂而言，在改善PS休息日（51.8%比44.4%）和达到肠内自主方面，56名患者中有7名（12.5%）与安慰剂组27名患者中有2名（7.4%）相比无统计学意义。

Apraglutide was generally well-tolerated. Topline safety results were generally consistent with the safety profile demonstrated in apraglutide studies to date.

阿帕鲁肽通常耐受性良好。Topline安全性结果通常与迄今为止阿帕鲁肽研究中证明的安全性一致。

“Patients with SBS-IF bear the dual burden of a devastating condition and a complex treatment regimen that includes hours of parenteral support, which significantly impacts their quality of life and carries a risk of severe complications such as infection,” said Michael Shetzline, M.D., Ph.D., chief medical officer, senior vice president and head of research and drug development at Ironwood Pharmaceuticals.

“SBS-IF患者承受着毁灭性疾病和复杂治疗方案的双重负担，其中包括数小时的肠胃外支持，这会严重影响他们的生活质量，并有感染等严重并发症的风险，”首席医疗官迈克尔·谢茨林（Michael Shetzline）说，Ironwood Pharmaceuticals高级副总裁兼研究和药物开发负责人。

“We believe these results demonstrate the potential for apraglutide to improve the standard of care for all adult patients with SBS dependent on parenteral support as the only GLP-2 with once-weekly administration, if approved. We are thankful to the patients and clinical investigators involved in the largest study of a GLP-2 analog in SBS-IF and will work with regulators on next steps with the goal of making apraglutide available to those living with this severe condition.”.

“我们相信这些结果表明，如果获得批准，阿帕鲁肽有可能改善所有依赖肠胃外支持的成年SBS患者的护理标准，因为它是唯一一种每周服用一次的GLP-2。我们感谢参与SBS-if中GLP-2类似物最大规模研究的患者和临床研究人员，并将与监管机构合作采取下一步行动目标是让患有这种严重疾病的人可以使用阿帕鲁肽。”

Ironwood looks forward to presenting additional data from the STARS study at upcoming medical conferences later this year.

Ironwood期待着在今年晚些时候即将举行的医学会议上提供STARS研究的更多数据。

About STARS

关于STARS

The STARS (STudy of ApRaglutide in SBS) pivotal Phase III trial represents the largest Phase III trial in SBS-IF to date.

STARS（SBS中阿帕鲁肽的研究）关键的III期临床试验代表了迄今为止SBS-IF中最大的III期临床试验。

This global, multicenter, double-blind, randomized, placebo-controlled trial evaluated the efficacy and safety of weekly subcutaneous injections of apraglutide in adult patients with SBS-IF. STARS enrolled 164 patients and dosed 163 stratified approximately 50/50 (stoma vs. colon-in continuity), then evaluated them over 24 weeks (stoma and colon-in-continuity populations) and 48 weeks (colon-in-continuity population only).

这项全球性，多中心，双盲，随机，安慰剂对照试验评估了成年SBS-IF患者每周皮下注射阿帕鲁肽的有效性和安全性。STARS招募了164名患者，剂量为163，分层约为50/50（连续性造口与结肠），然后在24周内对其进行评估（连续性人群中的造口和结肠）和48周（仅连续性人群中的结肠）。

Patients were randomized 2:1 to either once weekly apraglutide or placebo. The primary endpoint was relative change from baseline in actual weekly PS volume at week 24. Key secondary endpoints included patients who achieved a reduction from baseline of at least 1 day/week of PS at week 24 (all patients); relative change from baseline in actual weekly PS volume at week 24 (stoma population); patients who achieved a reduction from baseline of at least 1 day/week of PS at week 48 (colon-in-continuity population); and patients reaching enteral autonomy at week 48 (colon-in-continuity population)..

患者以2:1的比例随机分配到每周一次的阿帕鲁肽或安慰剂。主要终点是第24周实际每周PS量与基线的相对变化。关键的次要终点包括在第24周（所有患者）从基线至少减少1天/周PS的患者；第24周实际每周PS量与基线的相对变化（造口种群）；在第48周（连续性人群中的结肠）从基线至少减少1天/周PS的患者；以及在第48周达到肠内自主的患者（连续性人群中的结肠）。

The study was conducted in 18 countries with 68 active sites.

这项研究在18个国家进行，有68个活动地点。

About Short Bowel Syndrome (SBS)

关于短肠综合征（SBS）

SBS is a serious and chronic condition where there is diminished absorptive capacity for fluids and/or nutrients, sometimes requiring dependence on parenteral support to maintain health. Short bowel syndrome typically occurs because of extensive intestinal resection, and patients with SBS who are chronically dependent on parenteral support, also referred to as SBS with intestinal failure (SBS-IF), often experience significant quality of life impact and are at risk of severe complications such as infection.

SBS是一种严重的慢性疾病，对液体和/或营养物质的吸收能力降低，有时需要依赖肠胃外支持来维持健康。短肠综合征通常是由于广泛的肠切除而发生的，长期依赖肠外支持的SBS患者，也称为肠衰竭SBS（SBS-IF），通常会对生活质量产生重大影响，并有感染等严重并发症的风险。

An estimated 18,000 adult patients suffer from SBS-IF in the U.S., Europe and Japan, and have chronic dependence on PS, which significantly impacts quality of life and carries the risk of severe complications such as infection. Those with the most severe SBS-IF require PS infusions for up to 10 to 15 hours per day.

在美国，欧洲和日本，估计有18000名成年患者患有SBS-IF，并且长期依赖PS，这会严重影响生活质量，并有感染等严重并发症的风险。那些SBS-IF最严重的患者每天需要输注PS长达10至15小时。

SBS-IF is associated with frequent complications, significant morbidity and mortality, high economic burden and an impaired quality of life..

SBS-IF与频繁的并发症，显着的发病率和死亡率，高经济负担和生活质量受损有关。

Conference Call

电话会议

Ironwood will host a conference call and webcast today, Thursday, February 29, 2024 at 8:00 a.m. Eastern Time to discuss the topline results. Individuals interested in participating in the call should dial (800) 715-9871 (U.S. and Canada) or (646) 307-1963 (international) using conference ID number and event passcode 2684639.

Ironwood将于今天（2024年2月29日，星期四）东部时间上午8:00主持一次电话会议和网络广播，讨论最终结果。有兴趣参加呼叫的个人应使用会议ID号和活动密码2684639拨打（800）715-9871（美国和加拿大）或（646）307-1963（国际）。

To access the webcast, please visit the Investors section of Ironwood’s website at www.ironwoodpharma.com. The call will be available for replay via telephone starting at approximately 11:30 a.m. Eastern Time on February 29, 2024, running through 11:59 p.m. Eastern Time on March 14, 2024. To listen to the replay, dial (800) 770-2030 (U.S.

要访问网络广播，请访问Ironwood网站的投资者部分，网址为www.ironwoodpharma.com。电话将从2024年2月29日东部时间上午11:30左右开始，一直持续到2024年3月14日东部时间下午11:59。要收听重播，请拨打（800）770-2030（美国）。

and Canada) or (609) 800-9909 (international) using conference ID number 2684639. The archived webcast will be available on Ironwood’s website for 1 year beginning approximately one hour after the call has completed..

和加拿大）或（609）800-9909（国际），使用会议ID号2684639。存档的网络广播将在Ironwood的网站上提供一年，从通话结束后大约一小时开始。

About Apraglutide

关于Apraglutide

Apraglutide is an investigational, next-generation, long-acting synthetic GLP-2 analog being developed for a range of rare gastrointestinal diseases where GLP-2 can play a central role in addressing disease pathophysiology, including short bowel syndrome (SBS) and Acute Graft-Versus-Host Disease (aGVHD)..

Apraglutide是一种研究性的下一代长效合成GLP-2类似物，正在为一系列罕见的胃肠道疾病开发，其中GLP-2可以在解决疾病病理生理学方面发挥核心作用，包括短肠综合征（SBS）和急性移植物抗宿主病（aGVHD）。

About Ironwood Pharmaceuticals

关于Ironwood Pharmaceuticals

Ironwood Pharmaceuticals (Nasdaq: IRWD), an S&P SmallCap 600® company, is a leading global gastrointestinal (GI) healthcare company on a mission to advance the treatment of GI diseases and redefine the standard of care for GI patients. We are pioneers in the development of LINZESS® (linaclotide), which is the U.S.

Ironwood Pharmaceuticals（Nasdaq:IRWD）是一家标准普尔SmallCap 600®公司，是全球领先的胃肠道（GI）保健公司，其使命是推进胃肠道疾病的治疗并重新定义胃肠道患者的护理标准。我们是美国LINZESS®（利那洛肽）开发的先驱。

branded prescription market leader for adults with irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC) and is also indicated for the treatment of functional constipation in pediatric patients ages 6-17 years old. Ironwood is also advancing apraglutide, a next-generation, long-acting synthetic GLP-2 analog being developed for rare gastrointestinal diseases, including short bowel syndrome with intestinal failure (SBS-IF) dependent on PS as well as several earlier stage assets.

针对患有便秘的肠易激综合征（IBS-C）或慢性特发性便秘（CIC）的成年人的品牌处方市场领导者，也适用于治疗6-17岁儿科患者的功能性便秘。Ironwood也在推进阿帕鲁肽，这是一种下一代长效合成GLP-2类似物，正在开发用于罕见的胃肠道疾病，包括依赖PS的短肠综合征伴肠衰竭（SBS-IF）以及一些早期资产。

Building upon our history of GI innovation, we keep patients at the heart of our R&D and commercialization efforts to reduce the burden of GI diseases and address significant unmet needs. Founded in 1998, Ironwood Pharmaceuticals is headquartered in Boston, Massachusetts, with a site in Basel, Switzerland..

在我们胃肠道创新历史的基础上，我们将患者置于研发和商业化努力的核心，以减轻胃肠道疾病的负担并解决重大未满足的需求。Ironwood Pharmaceuticals成立于1998年，总部位于马萨诸塞州波士顿，总部位于瑞士巴塞尔。

We routinely post information that may be important to investors on our website at www.ironwoodpharma.com. In addition, follow us on X and on LinkedIn.

我们经常在我们的网站www.ironwoodpharma.com上发布对投资者可能很重要的信息。此外，请在X和LinkedIn上关注我们。