GLP-1新适应症落地，儿科进展与海外临床并进
本期导读 / CONTENTS
01 产品获批：司美MASH获批、替尔泊肽心血管新适应症
02 临床进展：Semaglutide、CagriSema、Amycretin、Enlicitide
03 监管动态：FDA 发布17个多肽仿制药个药指南
APPROVALS
产品获批
司美格鲁肽（诺和盈）MASH适应症获中国NMPA批准，成为国内首个获批该适应症的GLP-1受体激动剂
Semaglutide (Wegovy) MASH indication approved by NMPA—China's first GLP-1 receptor agonist approved for MASH
诺和诺德宣布司美格鲁肽注射液（商品名：诺和盈®）用于代谢相关脂肪性肝炎（MASH）的上市申请获国家药品监督管理局（NMPA）批准[1]，适用人群为MASH伴中重度肝纤维化（F2–F3期）的非肝硬化成人患者。该批准基于ESSENCE三期研究（第1部分）：在1,197例经肝活检确诊伴F2/F3纤维化的患者中，约63%的司美格鲁肽组实现「MASH缓解且肝纤维化未恶化」，安慰剂组约34%；约37%实现「肝纤维化改善且MASH未恶化」，安慰剂组约22%。这一获批将司美格鲁肽的循证范围由体重管理与心血管健康延伸至肝脏疾病领域[2]。
EN
Novo Nordisk announced that the marketing authorization application for semaglutide injection (Wegovy®) in metabolic dysfunction–associated steatohepatitis (MASH) was approved by the National Medical Products Administration (NMPA). The indication covers non-cirrhotic adult patients with MASH accompanied by moderate-to-severe hepatic fibrosis (stage F2–F3). The approval is supported by Part 1 of the phase 3 ESSENCE trial. Among 1,197 liver biopsy-confirmed patients with F2/F3 fibrosis, approximately 63% of patients in the semaglutide group achieved MASH resolution with no worsening of hepatic fibrosis, compared with around 34% in the placebo group. About 37% attained hepatic fibrosis improvement with no worsening of MASH in the semaglutide group, versus 22% in the placebo group. This approval extends semaglutide's evidence base beyond weight management and cardiovascular health to the field of liver disease.
FDA批准替尔泊肽心血管风险降低新适应症，成为首个获批心脏保护适应症的GIP/GLP-1双受体激动剂
FDA approved tirzepatide cardiovascular risk reduction indication—the first GIP/GLP-1 dual agonist with an approved cardiac-protection label
FDA批准Mounjaro（替尔泊肽）用于降低伴有高心血管风险的2型糖尿病成人发生主要不良心血管事件（MACE）的风险[3]，使其成为首个获批心血管适应症的GIP/GLP-1双受体激动剂。该批准基于SURPASS-CVOT三期研究（13,299例、中位随访约4年）[4]：替尔泊肽相对度拉糖肽达到MACE非劣效（HR 0.92，95% CI 0.83–1.01），全因死亡、心梗、卒中等终点均呈更低趋势但未达统计学优效[5]。
EN
The FDA has approved Mounjaro (tirzepatide) to reduce the risk of major adverse cardiovascular events (MACE) in adults with type 2 diabetes at high cardiovascular risk, making it the first GIP/GLP-1 dual receptor agonist approved for cardiovascular indication. This approval was based on the Phase 3 SURPASS-CVOT trial (13,299 participants; median follow-up of approximately 4 years): tirzepatide met the non-inferiority criterion for MACE versus dulaglutide (HR 0.92, 95% CI 0.83–1.01), and endpoints including all‑cause mortality, myocardial infarction, and stroke all showed a lower trend but did not reach statistical superiority.
CLINICAL
临床进展
诺和诺德 STEP Young：司美格鲁肽用于6–12岁以下肥胖儿童III期达主要终点，约四成患儿BMI降至肥胖阈值以下
Novo Nordisk STEP Young: semaglutide phase 3 meets primary endpoint in children aged 6 to <12, with ≈40% achieving BMI below the obesity threshold
诺和诺德公布STEP Young III期首个结果，评估每周一次皮下注射司美格鲁肽联合低热量饮食与增加体力活动用于6至12岁以下肥胖儿童[6]。试验达到主要终点：第68周时司美格鲁肽组BMI降幅优于安慰剂组。基于试验产品估计目标，40.4%的司美格鲁肽治疗儿童BMI降至肥胖阈值以下（即不再归类为肥胖），安慰剂组为0%。该研究为随机、双盲、安慰剂对照、多国试验，共入组165例儿童，两组均接受生活方式干预；入组时超过85%的患儿为II级或III级重度肥胖。安全性与既往司美格鲁肽及利拉鲁肽的儿科、成人试验一致，未发现新的安全性信号，生长与青春期发育亦无相关担忧。这是GLP-1多肽类药物首次在低龄儿童群体交出注册性数据，提示其适用人群持续向更低年龄与长期用药拓展。
EN
Novo Nordisk announced the first results from the phase 3 STEP Young trial, evaluating once-weekly subcutaneous semaglutide combined with a low-calorie diet and increased physical activity in children aged 6 to under 12 years with obesity. The trial met its primary endpoint: the reduction in BMI was greater in the semaglutide group than in the placebo group at Week 68. Per the trial’s investigational‑product estimand, 40.4% of children treated with semaglutide achieved a BMI below the obesity threshold (i.e., no longer classified as obese), compared with 0% in the placebo group. STEP Young was a randomized, double-blind, placebo-controlled, multinational trial that enrolled a total of 165 children. Lifestyle intervention was provided to both groups, and over 85% of participants had Class II or Class III severe obesity at baseline. The safety profile was consistent with previous pediatric and adult trials of semaglutide and liraglutide. No new safety signals were identified, and there were no concerns related to growth or pubertal development. This marks the first registrational data for GLP-1 peptide agents in younger children, indicating an ongoing expansion of eligible populations toward younger age groups and long-term use.
诺和诺德 CagriSema两项III期顶线齐发：REIMAGINE 5头对头优效于替尔泊肽5 mg，REDEFINE 9 单药减重21.0%
Novo Nordisk reports CagriSema topline from two phase 3 trials: REIMAGINE 5 superior to tirzepatide 5 mg head-to-head, REDEFINE 9 achieves 21.0% weight loss as monotherapy
诺和诺德公布每周一次 CagriSema（卡格林肽与司美格鲁肽的固定复方）两项III期顶线结果。在 REIMAGINE 5（2型糖尿病人群）中，CagriSema 1.0 mg/1.0 mg 治疗60周后实现12.4%的估计平均体重降幅，优于替尔泊肽5 mg组的9.1%，达到优效终点；其HbA1c降幅（1.71% vs 1.67%）亦证实相对替尔泊肽的非劣效性[7]。在REDEFINE 9（超重或肥胖成人）中，CagriSema 1.0 mg/1.0 mg治疗68周后实现21.0%的体重降幅，安慰剂组为2.0%，达到主要优效终点，并在收缩压、腰高比与空腹血脂等预设支持性终点上较安慰剂显示更大改善[8]。两项试验整体耐受性良好，安全性特征与既往研究一致。CagriSema 的FDA体重管理上市申请（NDA）已于 2025年12月提交，预计2026年第四季度作出审批决定。
EN
Novo Nordisk announced topline results from two phase 3 trials of once-weekly CagriSema, a fixed-dose combination of cagrilintide and semaglutide. In REIMAGINE 5 (participants with type 2 diabetes), CagriSema 1.0 mg/1.0 mg achieved an estimated mean weight reduction of 12.4% after 60 weeks of treatment, surpassing the 9.1% reduction in the tirzepatide 5 mg group and meeting the superiority endpoint. The reduction in HbA1c (1.71% vs 1.67%) also confirmed non-inferiority versus tirzepatide. In REDEFINE 9 (participants with overweight or obesity), CagriSema 1.0 mg/1.0 mg achieved a 21.0% weight reduction after 68 weeks of treatment versus 2.0% in the placebo group, meeting the primary superiority endpoint, with greater improvements versus placebo group on prespecified supportive endpoints including systolic blood pressure, waist-to-height ratio and fasting lipid parameters. Both trials demonstrated an overall favourable tolerability profile, with safety findings consistent with previous studies. Novo Nordisk submitted an NDA to the FDA for CagriSema for weight management in December 2025, with a regulatory decision anticipated in Q4 2026.
诺和诺德在日本启动Amycretin（zenagamtide）肥胖III期临床AMAZE 10，全球三期布局进一步推进
Novo Nordisk initiates phase 3 obesity trial AMAZE 10 of amycretin (zenagamtide) in Japan, advancing the global phase 3 program
诺和诺德启动针对日本超重或肥胖人群的 III 期临床试验 AMAZE 10（研究药物 zenagamtide，即 Amycretin；登记号 NCT07822061，计划入组400例）[9]。Amycretin为单分子 GLP-1/胰淀素双受体激动剂，提供每周皮下注射与每日口服两种剂型；此次日本III期是其全球AMAZE/AMBITION三期项目的新进展，显示该下一代减重资产的临床推进持续加速。
EN
Novo Nordisk has initiated the Phase 3 AMAZE 10 trial for overweight or obesity participants in Japan (investigational product: zenagamtide, also known as Amycretin; ClinicalTrials.gov identifier NCT07822061, planned enrollment of 400 subjects). Amycretin is a single-molecule GLP-1/amylin dual receptor agonist available in two formulations: once-weekly subcutaneous injection and once-daily oral administration. This Japanese Phase 3 trial marks new progress in its global AMAZE/AMBITION Phase 3 program, demonstrating accelerated clinical advancement of this next-generation weight-loss asset.
默沙东启动恩利西肽（enlicitide）印度III期高脂血症研究，全球首款口服PCSK9抑制剂海外临床提速
Merck initiates enlicitide phase 3 hyperlipidemia study in India, accelerating the world's first oral PCSK9 inhibitor's global development
默沙东（Merck & Co.）启动恩利西肽（enlicitide/Lipfendra，靶向PCSK9的口服大环多肽）针对印度成人高脂血症患者的III期临床试验（NCT07821944，随机、双盲、安慰剂对照，目标入组150例）[10]，评估enlicitide decanoate 的有效性与安全性。恩利西肽于2026年7月获FDA批准，成为全球首款口服PCSK9抑制剂。
EN
Merck & Co. has initiated a Phase 3 clinical trial of enlicitide (Lipfendra, an oral macrocyclic peptide targeting PCSK9) in adults with hyperlipidemia in India (NCT07821944; randomized, double-blind, placebo-controlled; target enrollment of 150 subjects) to evaluate the efficacy and safety of enlicitide decanoate. Enlicitide was approved by the FDA in July 2026, becoming the world's first oral PCSK9 inhibitor.
REGULATORY
监管动态
FDA发布17个多肽仿制药个药指南草案，明确司美与替尔泊等品种的仿制申报路径
FDA publishes draft product-specific guidance for 17 generic peptides, clarifying the ANDA pathway for semaglutide, tirzepatide, and others
FDA发布涵盖司美格鲁肽、替尔泊肽等17个已上市多肽品种的仿制药个药指南草案[11]，公开征求意见期截至2026-09-28。指南明确了检测标准、对比分析评估与免疫原性考量，是继2023年多肽指南更新后较为重要的仿制药政策动作，适逢司美格鲁肽专利悬崖（2031年）与替尔泊肽最早仿制窗口（2027年12月）临近，将直接影响美国ANDA申报策略。
EN
The FDA published a draft product-specific guidance for generics covering 17 marketed peptide products including semaglutide and tirzepatide. The public comment period closes on September 28, 2026. The guidance clarifies testing standards, comparative analytical assessment and immunogenicity considerations. It represents a major generic policy update following the revision of the peptide guidance in 2023. As the patent cliff for semaglutide (2031) and the earliest generic entry window for tirzepatide (December 2027) approach, this document will directly shape ANDA submission strategies in the United States.
参考文献 / REFERENCES
[1] Novo Nordisk China. 中国首个且唯一！诺和盈® 获批代谢相关脂肪性肝炎适应症[EB/OL]. (2026-09-10)[2026-09-28].
[2] Novo Nordisk China. China's first and only! Wegovy® approved for the treatment of metabolic dysfunction–associated steatohepatitis[EB/OL]. (2026-09-10)[2026-09-28].
[3] U.S. Food and Drug Administration. Mounjaro (tirzepatide) approval letter: supplemental new drug application for reduction of major adverse cardiovascular events risk in type 2 diabetes[EB/OL]. (2026-08-28)[2026-09-28].
[4] NICHOLLS S J, PAVO I, BHATT D L, et al. Cardiovascular outcomes with tirzepatide versus dulaglutide in type 2 diabetes[J]. New England Journal of Medicine, 2025, 393(24): 2409-2420. DOI:10.1056/NEJMoa2505928.
[5] The Medical Letter. A cardiovascular indication for tirzepatide (Mounjaro)[J]. The Medical Letter on Drugs and Therapeutics, 2026, 68(5133): 1. DOI:10.58347/tml.2026.5133a.
[6] NOVO NORDISK A/S. STEP Young phase 3 data: 40.4% of children living with obesity achieved a BMI below the obesity threshold with semaglutide and lifestyle modification[EB/OL]. (2026-09-07)[2026-09-28].
[7] 诺和诺德中国。诺和 CagriSema 在 REIMAGINE 5 试验中实现较替尔泊肽更优的减重效果 [EB/OL]. (2026-09-23)[2026-09-28].
[8] NOVO NORDISK CHINA. CagriSema demonstrates superior weight reduction versus tirzepatide in REIMAGINE 5[EB/OL]. (2026-09-23)[2026-09-28].
[9] ClinicalTrials.gov. NCT07822061: efficacy and safety of NNC0487-0111 s.c. once-weekly in Japanese participants with overweight or obesity (AMAZE 10)[DB/OL]. (2026-09-16)[2026-09-28].
[10] ClinicalTrials.gov. NCT07821944: a phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of enlicitide decanoate in adults with hyperlipidemia in India[DB/OL]. (2026-09-16)[2026-09-28].
[11] U.S. Food and Drug Administration. Draft guidance for industry: 17 generic peptide products (including semaglutide and tirzepatide)[EB/OL]. (2026-09)[2026-09-28].