- News builds on previously announced primary endpoint, which showed up to 83.0% of adults achieved statistically significant improvement in metabolic dysfunction-associated steatohepatitis (MASH) versus placebo (18.2%).

- 新闻基于之前宣布的主要终点，显示高达83.0%的成人在代谢功能障碍相关性脂肪肝病（MASH）方面的统计学显著改善，而安慰剂组为18.2%。

- New data on the secondary endpoint shows up to 52.3% of adults with fibrosis stages F1, F2 and F3 had improvement in fibrosis due to MASH.

- 次要终点的新数据显示，高达52.3%的纤维化阶段F1、F2和F3的成人因MASH而纤维化状况有所改善。

- Additional sub-analysis shows up to 64.5% of adults with fibrosis stages F2 and F3 (moderate to advanced scarring) achieved an improvement in fibrosis without worsening of MASH.

- 额外的亚分析显示，高达64.5%的纤维化阶段F2和F3（中度至重度瘢痕）的成人在MASH没有恶化的情况下纤维化状况得到了改善。

- Survodutide to advance into Phase III MASH study; results reinforce its potential as a best-in-class MASH treatment and, with ongoing trials in obesity,2 could lead to clinically meaningful benefits across the cardiovascular, renal, and metabolic spectrum.

- 将进入 III 期 MASH 研究；结果增强了它作为一流 MASH 治疗的潜力，并且，随着在肥胖方面的持续试验，可能会在心血管、肾脏和代谢谱系中带来临床上有意义的益处。

Boehringer Ingelheim today announced breakthrough results from a survodutide Phase II trial sub-analysis that demonstrate up to 64.5% of adults with fibrosis stages F2 and F3 (moderate to advanced scarring) achieved an improvement in fibrosis without worsening of metabolic dysfunction-associated steatohepatitis (MASH), versus 25.9% with placebo after 48 weeks of treatment [response difference: 38.6% (95% CI 18.1% - 59.1%), p=0.0005]. F2 and F3 patient populations are at increased risk of developing liver-related complications.

勃林格殷格翰今日宣布，在一项Survodutide II期试验的亚分析中取得了突破性结果，表明在接受48周治疗后，高达64.5%的F2和F3纤维化阶段（中度至重度瘢痕）的成年人在纤维化方面有所改善，而没有加剧与代谢功能障碍相关的脂肪肝病（MASH），相比之下，安慰剂组的比例为25.9%[响应差异：38.6%（95% CI 18.1% - 59.1%），p=0.0005]。F2和F3患者群体发展成肝相关并发症的风险增加。

The full data results were presented today at the European Association for the Study of the Liver Congress (EASL) 2024 and published simultaneously in The New England Journal of Medicine The secondary endpoint shows that up to 52.3% of adults treated with survodutide (BI 456906) achieved a significant improvement in liver scarring (fibrosis) stages F1, F2 and F3 (mild to moderate or advanced scarring), versus 25.8% with placebo after 48 weeks of treatment [response difference: 26.5% (95% CI 8.37% – 44.66%), p<0.01].

完整的数据结果今天在2024年欧洲肝脏研究协会大会（EASL）上发表，并同时在《新英格兰医学杂志》上发表。次要终点显示，在接受Survodutide（BI 456906）治疗的成年人中，高达52.3%的人在F1、F2和F3（轻度至中度或重度瘢痕）的肝脏瘢痕（纤维化）阶段取得了显著改善，相比之下，安慰剂组的比例为25.8%[响应差异：26.5%（95% CI 8.37% – 44.66%），p<0.01]。

Today’s news follows data announced earlier this year when the trial met its primary endpoint. These results demonstrated that up to 83.0% of adults achieved a statistically significant improvement of MASH versus placebo (18.2%), reinforcing the potential of survodutide as a best-in-class treatment [response difference: 64.8% (95% CI 51.1% – 78.6%), p<0.0001].

今日的新闻是在本年初宣布的试验数据之后发布的，当时试验达到了其主要终点。这些结果表明，高达83.0%的成人在MASH方面的统计学显著改善超过了安慰剂组（18.2%），这增强了Survodutide作为一流治疗方案的潜力[响应差异：64.8%（95% CI 51.1% – 78.6%），p<0.0001]

Survodutide is a glucagon/GLP-1 receptor dual agonist with a novel mechanism of action, and the first to show this level of fibrosis benefit in a Phase II MASH trial after 48 weeks of treatment. The glucagon agonist component in survodutide has the potential to increase energy expenditure7,8 and has a direct impact in the liver, which could contribute to the improvement of fibrosis.5 The GLP-1 agonist component decreases appetite while increasing fullness and satiety.

Survodutide 是一种胰高血糖素/GLP-1受体双重激动剂，具有新颖的作用机制，并且在48周治疗后的II期MASH试验中首次显示出这种程度的纤维化益处。Survodutide中的胰高血糖素激动剂成分有潜力增加能量消耗，并对肝脏有直接影响，这可能有助于纤维化的改善。GLP-1激动剂成分则在减少食欲的同时增加饱腹感和满足感。

An improvement was measured as a decrease of at least one stage in fibrosis after 48 weeks of treatment in this trial. Fibrosis is a measurement of the progression of MASH, a progressive disease impacting more than 115 million people worldwide. MASH is caused by inflammation of the liver that can lead to fibrosis, and severe tissue scarring (cirrhosis) can substantially increase the risk of end-stage liver disease and liver cancer. A liver transplant may be the only treatment option at this stage, which can place significant financial strain on healthcare systems. Liver fibrosis typically worsens slowly, and it is easy to go undetected if the fibrosis is not extensive. The reversal of liver fibrosis is often challenging for advanced stages of scarring and may not be possible for cirrhosis.

在这项试验中，改善被定义为在接受48周治疗后纤维化程度至少降低一个阶段。纤维化是衡量MASH进展的指标，MASH是一种进展性疾病，全球影响超过1.15亿人。MASH由肝脏炎症引起，可能导致纤维化，严重的组织瘢痕（肝硬化）可以大幅增加末期肝病和肝癌的风险。在这个阶段，肝脏移植可能是唯一的治疗选择，这可能会给医疗系统带来重大的经济压力。肝脏纤维化通常恶化得很慢，如果纤维化不广泛，它很容易未被检测到。对于瘢痕的高级阶段，肝脏纤维化的逆转通常是具有挑战性的，对于肝硬化可能是不可能的。

In this Phase II trial, survodutide also demonstrated significance versus placebo for all other secondary endpoints after 48 weeks of treatment. Actual treatment results showed that up to 87.0% of adults achieved at least a 30% relative reduction in liver fat versus 19.7% with placebo, as well as a relative reduction in liver fat content of up to 64.3% versus 7.3% with placebo. The absolute change from baseline in Non-alcoholic Fatty Liver Disease Activity Score (NAS, which is used to measure improvement in MASH) in actual treatment results was up to -3.3 with survodutide versus -0.4 with placebo.

在这项II期试验中，Survodutide在48周治疗后对所有其他次要终点与安慰剂相比也显示出显著性差异。实际治疗结果显示，高达87.0%的成人实现了至少30%的肝脏脂肪含量相对减少，而安慰剂组为19.7%，同时肝脏脂肪含量相对减少了高达64.3%，而安慰剂组为7.3%。在非酒精性脂肪肝病活动评分（NAS，用于衡量MASH的改善情况）的实际治疗结果中，与基线相比的绝对变化在Survodutide治疗下高达-3.3，而安慰剂组为-0.4。

“Today’s breakthrough fibrosis results further reinforce survodutide’s potential as a best-in-class treatment for people living with MASH. We will advance quickly into Phase III trials,” said Carinne Brouillon, Head of Human Pharma, Boehringer Ingelheim. “New treatments are urgently needed for MASH, a disease connected with cardiovascular, renal and metabolic conditions like obesity, and we are excited to continue these important discussions with healthcare authorities.”

“今日在纤维化方面的突破性结果进一步强化了Survodutide作为MASH患者一流治疗方案的潜力。我们将迅速进入III期试验，”勃林格殷格翰人类制药部门负责人Carinne Brouillon表示。“MASH是一种与心血管、肾脏和代谢状况如肥胖有关的疾病，迫切需要新的治疗方法，我们很高兴能继续与医疗保健当局进行这些重要的讨论。”

Survodutide is licensed to Boehringer Ingelheim from Zealand Pharma, with Boehringer solely responsible for development and commercialization globally. Zealand has a co-promotion right in the Nordic countries.

Survodutide 是从Zealand Pharma授权给勃林格殷格翰的，勃林格殷格翰全权负责全球的开发和商业化。Zealand在北欧国家拥有共同推广权。

In this trial, survodutide demonstrated safety data consistent with GLP-1 based molecules, with no new safety data concerns. Survodutide was granted U.S. Food and Drug Administration (FDA) Fast Track Designation in 2021, and the European Medicines Agency (EMA) granted access to the Priority Medicine (PRIME) Scheme for MASH with fibrosis in November last year.

在这项试验中，Survodutide展示的安全性数据与基于GLP-1的分子一致，没有新的安全数据问题。Survodutide在2021年获得了美国食品药品监督管理局（FDA）的快速通道认定，并且欧洲药品管理局（EMA）在去年11月为伴有纤维化的MASH授予了优先药物（PRIME）计划的准入。

Survodutide is also being explored in five Phase III studies for people living with overweight and obesity, both of which are associated with MASH. An additional Phase III trial is evaluating if survodutide helps people living with overweight or obesity, with a confirmed or presumed diagnosis of MASH, reduce liver fat and lose weight.

Survodutide 也在五项III期研究中被探索用于治疗患有超重和肥胖的人群，这两者都与MASH有关。另外一项III期试验正在评估Survodutide是否能帮助确诊或疑似MASH的超重或肥胖人群减少肝脏脂肪并减轻体重。