整理 | GLP1减重宝典内容团队 礼来今日公布其 III 期临床试验 TRIUMPH-4 的积极顶线结果。该研究评估了 retatrutide 两个最高剂量（9 mg 与 12 mg）在无糖尿病 的超重或肥胖成人、合并膝骨关节炎人群中的安全性与疗效，并作为健康饮食和运动的辅助治疗方案。 TRIUMPH-4 是一项全球注册性研究，84% 的受试者基线 BMI ≥35 kg/m²。结果显示，两种剂量的 retatrutide 在所有主要及关键次要终 点上均显著优于安慰剂，在 68 周时实现了大幅体重下降，同时明显改善疼痛与身体功能。 在共同主要终点方面： 平均体重最高下降 28.7%（约 71.2 磅）、 膝关节疼痛评分（WOMAC）最高下降 4.5 分，降幅达 75.8%、 这意味着 retatrutide 不仅显著降低体重，还直接改善了肥胖相关的结构性并发症。 礼来心血管与代谢健康业务总裁 Kenneth Custer 博士表示："肥胖合并膝骨关节炎的患者，往往长期忍受疼痛和活动受限，最终可能不 得不接受关节置换手术。TRIUMPH-4 的结果凸显了 retatrutide 作为首创三重激动剂，在体重、疼痛 ...

Core Viewpoint - Protagonist Therapeutics has selected PN-477 as its primary development candidate for obesity treatment, which is a triple agonist peptide targeting GLP-1, GIP, and glucagon (GCG) receptors, offering both efficacy and convenience through oral or subcutaneous administration [2][4]. Group 1: Drug Development and Efficacy - PN-477 has completed extensive preclinical evaluations, demonstrating positive effects in various animal models of obesity and blood glucose control, including diet-induced obese mice, normal dogs, and crab-eating macaques [4]. - The drug exhibits strong activation of GLP-1, GIP, and GCG receptors in vitro, indicating its potential effectiveness [4]. - PN-477's pharmacodynamic properties and overall performance make it suitable for parallel development as both a daily oral medication (PN-477o) and a weekly injection (PN-477sc) [4]. Group 2: Clinical Trials and Future Plans - The Investigational New Drug (IND) application is currently underway, with the first phase of clinical trials expected to start in the second quarter of 2026 [4]. - Protagonist Therapeutics plans to submit a New Drug Application (NDA) for its other candidates in 2025, indicating a robust pipeline [6][7]. Group 3: Market Position and Competitive Advantage - Despite the dominance of GLP-1 receptor agonists in the market, there is room for improvement, and a triple agonist like PN-477 could provide a significant breakthrough in obesity treatment by offering an oral option alongside injectable therapies [6]. - PN-477 is anticipated to reduce fat mass while preserving lean body mass and improving tolerability and comorbidities, positioning it as a potential blockbuster product for the company [6]. Group 4: Company Overview - Protagonist Therapeutics is an integrated biopharmaceutical company focused on drug discovery and late-stage development, with two novel candidates in Phase III clinical trials and plans for NDA submissions in 2025 [6][7]. - The company is also advancing several preclinical peptide drug development projects, including PN-881 and oral hepcidin [7].