MET-097

编者按：近年来，凭借代谢稳定性高、靶点亲和力强以及生物特异性优异等优势，多肽疗法正迅速崛起为全球新药研发的重要方向。从GLP-1类代谢疾病疗法持续取得突破，到肿瘤、神经系统疾病及免疫疾病等领域不断涌现的新型多肽分子，多肽药物的研发版图正在不断拓展。为了更好地满足全球合作伙伴的研发需求，药明康德围绕多肽及其相关化学偶联药物构建了一体化解决方案，覆盖定制合成、共价连接、工艺开发以及CMC等关键环节，并提供药代动力学分析和免疫原性检测等整合生物分析解决方案，为发现和开发多肽及复杂多肽偶联药物提供有力支持。本文将盘点2026年第一季度全球多肽疗法在监管审批、临床研究以及产业合作等方面的重要进展，并结合相关技术挑战，带您了解这一快速发展领域的最新动态与趋势。 监管进展 2026年第一季度，多肽疗法在全球范围内迎来多项重要监管进展。其中，GLP-1类疗法继续在肥胖及相关疾病领域取得突破。诺和诺德（Novo Nordisk）高剂量司美格鲁肽Wegovy HD（7.2 mg）注射剂在本季度获得美国FDA批准，用于已耐受2.4 mg剂量治疗至少4周、且仍需进一步减重的肥胖患者。与此同时，司美格鲁肽（商品名Kayshild）获得欧洲药品管理局（EMA）人用药品委员会（CHMP）推荐有条件批准，用于治疗伴有肝纤维化的非肝硬化性代谢功能障碍相关脂肪性肝炎（MASH），预计将在今年4月正式获批。根据新闻稿介绍，Kayshild有望成为首个获EMA批准用于MASH适应症的GLP-1类药物。 此外，加拿大卫生部（Health Canada）在今年1月批准司美格鲁肽口服片剂（商品名Rybelsus），用于降低患有2型糖尿病且已确诊心血管疾病或具有高心血管风险的成人患者发生主要不良心血管事件（MACE，包括心血管死亡、非致死性心肌梗死或非致死性卒中）的风险。 在非GLP-1类疗法方面，多款多肽药物也取得关键监管突破。Ascendis Pharma旗下Yuviwel（navepegritide；TransCon CNP）获得美国FDA加速批准，用于治疗2岁及以上且骨骺尚未闭合的软骨发育不全儿童。根据公司新闻稿，该药物为首个获批用于该患者人群、且每周一次给药的治疗方案。 同样在3月，强生（Johnson & Johnson）与Protagonist Therapeutics公司联合开发的口服多肽疗法Icotyde（icotrokinra）获得FDA批准，用于一线治疗中重度斑块状银屑病（PsO）成人患者，以及12岁及以上、体重至少40 kg且适合接受全身治疗或光疗的儿童患者。根据新闻稿，Icotyde是首个能够精准阻断IL-23受体的靶向口服多肽药物。 此外，Rhythm Pharmaceuticals旗下多肽药物Imcivree（setmelanotide）的扩展适应症也在本季度获得FDA批准，用于治疗成人及4岁及以上儿童获得性下丘脑性肥胖（HO），以降低过多体重并长期维持减重效果。同样值得关注的是，欧盟委员会（EC）批准Sobi与Apellis Pharmaceuticals联合开发的Aspaveli（pegcetacoplan），用于与肾素-血管紧张素系统（RAS）抑制剂联合治疗12至17岁青少年及成人C3肾小球病（C3G）或原发性免疫复合物型膜增生性肾小球肾炎（IC-MPGN）。 临床进展 在临床研究方面，GLP-1相关疗法仍是本季度多肽研发最活跃的领域之一，多家药企在肥胖及代谢疾病治疗方向持续取得进展。礼来（Eli Lilly and Company）宣布，其潜在“first-in-class”三重激素受体激动剂retatrutide在3期试验中取得积极结果。该分子可同时靶向葡萄糖依赖性促胰岛素多肽（GIP）、胰高血糖素样肽-1（GLP-1）以及胰高血糖素受体。研究分析显示，2型糖尿病患者在接受每周一次retatrutide治疗40周后，糖化血红蛋白（A1C）平均下降1.7–2.0个百分点，而最高剂量组患者的平均体重下降达到16.8%（36.6磅）。 与此同时，辉瑞（Pfizer）的长效GLP-1受体激动剂PF-08653944（PF'3944，曾用名MET-097i）也在2b期试验中取得积极结果。研究显示，所有四种剂量方案在主要终点——从随机分组至第28周的体重降低——方面均显著优于安慰剂（P<0.001）。值得关注的是，在切换至每月给药后，减重效果依然强劲且持续，在第28周尚未出现平台期，提示该疗法具备每月一次给药的潜力。目前，PF'3944的多项3期试验正在推进中。 此外，Viking Therapeutics旗下GIP/GLP-1双重受体激动剂VK2735的2期试验结果发表于《肥胖》期刊，其3期试验也在本季度完成患者招募。Altimmune旗下候选药物pemvidutide则在今年年初获得FDA突破性疗法认定，用于治疗MASH。公司已与FDA就3期注册试验关键设计达成一致，即将启动针对中至重度肝纤维化MASH患者的3期研究。 与此同时，诺和诺德宣布其固定剂量联合疗法CagriSema在3期试验中，在减重与改善A1C方面均优于司美格鲁肽。CagriSema由长效胰淀素类似物cagrilintide（2.4 mg）与司美格鲁肽（2.4 mg）组成。此外，Zealand Pharma与艾伯维（AbbVie）旗下的胰淀素靶向疗法petrelintide与ABBV-295也在本季度分别公布了用于治疗肥胖患者的2期与1期试验积极结果。 值得注意的是，GLP-1疗法的应用范围正在逐步拓展至代谢疾病之外。礼来在本季度宣布，其GLP-1/GIP双重受体激动剂Zepbound（tirzepatide）联合IL-17A单抗Taltz（ixekizumab），在两项分别针对中重度斑块状银屑病及活动性银屑病关节炎（PsA）肥胖或超重患者的3期试验中均达到主要终点。这些结果显示，GLP-1类疗法有望与银屑病生物制品形成新的联合治疗策略。 除GLP-1相关疗法外，本季度多项多肽疗法也在其他疾病领域取得进展。例如，Priavoid旗下靶向β-淀粉样蛋白（Aβ）寡聚体的口服多肽疗法PRI-002在2期试验中显示，其淀粉样相关影像学异常（ARIA）发生率与既往3期研究中安慰剂组水平相当。此外，一项1/2期试验结果显示，一名同时患有家族性腺瘤性息肉病（FAP）及相关硬纤维瘤的患者在接受Parabilis Medicines潜在“first-in-class”多肽疗法zolucatetide治疗60周后，十二指肠息肉病变显著改善。与治疗前评估相比，该患者息肉数量和大小均明显减少，疾病分期由Spigelman II期降至I期，同时硬纤维瘤直径减少了52.2%。根据新闻稿，zolucatetide是首个直接抑制β-catenin与TCF相互作用的抑制剂。 研发合作与融资进展 在产业合作方面，本季度多家大型药企围绕多肽疗法达成金额达数亿美元甚至数十亿美元的合作协议。今年1月，阿斯利康（AstraZeneca）与石药集团达成最高可达35亿美元的战略合作，双方将共同推进覆盖肥胖症与2型糖尿病的8项下一代疗法研发。根据协议，双方将首先推进其中4个项目，这些项目将结合石药集团AI驱动的肽类药物发现平台以及其专有的LiquidGel每月一次给药平台技术。此外，诺华（Novartis）在2月与Unnatural Products（UNP）达成总金额超过17亿美元的大环肽合作，进一步加码这一新兴分子领域。 融资方面，多家创新公司也获得资本市场支持。Parabilis Medicines在今年初完成超过3亿美元的F轮融资，所获资金将用于推进zolucatetide的开发。同时，峰肽药业（Pinnacle Medicines）也于3月时完成8900万美元的B轮融资，用于加速管线的临床推进。 ▲2026年第一季度多肽药物领域部分投融资信息 一体化平台助力多肽药物创新 随着多肽疗法在肥胖、代谢疾病以及更多创新适应症中的研发不断推进，其分子设计也正变得愈发复杂。从脂肪酸修饰、PEG化，到蛋白融合与多肽偶联等策略，越来越多的新一代多肽分子通过结构改造实现更长半衰期或更优药效。然而，这些创新设计在带来治疗潜力提升的同时，也对药物开发过程中的生物分析提出了更高要求。特别是在临床研究阶段，如何准确解析多肽药物的体内暴露特征、免疫原性风险以及结构修饰带来的影响，已成为推动相关疗法顺利进入后期开发的重要基础。 在这一趋势下，能够同时支持药代动力学（PK）与免疫原性评价的系统化生物分析能力，正成为创新多肽药物研发的重要技术支撑。为帮助合作伙伴更好地应对这些挑战，药明康德生物分析部（BAS）依托高度成熟的生物分析技术平台，构建了面向新一代多肽药物开发需求的系统化分析解决方案，能够有效应对多肽分子在临床试验中药代动力学与免疫原性研究的复杂挑战。 随着多肽药物分子量增加、结构修饰增多及偶联形式日益复杂，其生物分析面临一系列特有挑战。例如，一方面，多肽在液相色谱串联质谱（LC-MS/MS）分析中通常呈现多电荷态分布及电离效率不均一，导致信号分散与离子抑制，从而影响检测灵敏度与方法稳健性；另一方面，多肽分子表位有限且与内源性肽序列高度同源，往往表现为免疫原性较低、特异性抗体制备困难，同时在配体结合分析（LBA）中易出现内源性干扰与交叉反应，增加免疫原性评价的复杂性。此外，脂肪酸修饰、PEG化或蛋白融合等结构改造在延长半衰期的同时，也可能引入新的免疫原性风险（如抗PEG抗体），对抗药抗体（ADA）与中和抗体（NAb）检测提出更高要求。 针对上述行业痛点，药明康德生物分析部整合高灵敏度LC-MS/MS、免疫捕获-质谱、ELISA/MSD平台及细胞功能分析方法，实现PK分析、抗药抗体（ADA）与中和抗体（NAb）评价的一体化支持。通过优化样本前处理策略、建立免疫捕获-质谱联用技术及基于胰蛋白酶消化的bottom-up分析方法，可显著提升检测灵敏度并降低基质干扰，在复杂修饰多肽及长链多肽分析中表现出良好的方法特异性与稳健性。同时，针对多肽药物免疫原性评价中的低免疫原性与高同源性带来的检测难点，团队建立了分层（tiered）免疫原性评价体系，整合桥式（bridging）ADA检测、确认实验及滴度分析，并结合酸解离（ACE）、MRD优化等策略提升药物耐受性与检测灵敏度；通过优化标记试剂设计及方法学条件，有效降低内源性干扰与非特异性结合，并结合细胞功能性NAb分析方法，实现从ADA筛查到中和效应评价的全流程覆盖，从而系统性支持复杂修饰多肽及偶联多肽药物的免疫原性风险评估。 药明康德生物分析技术平台已成功支持GLP-1类似物、胰岛素类似物等新一代多肽药物的临床PK研究及免疫原性评估，形成覆盖方法开发、验证到样本检测的端到端能力。依托标准化流程与多技术协同优势，药明康德生物分析部能够为合作伙伴提供高灵敏度、高可靠性的多肽药物生物分析支持，加速创新多肽疗法从研究阶段迈向临床开发。 Multiple FDA Approvals and Hundreds of Millions in Investments: Peptide Therapeutics See Significant Progress in Q1 In recent years, peptide therapeutics have rapidly emerged as a major direction in global drug discovery, driven by their high metabolic stability, strong target affinity, and excellent biological specificity. From continued breakthroughs in glucagon-like peptide-1 (GLP-1)–based therapies for metabolic diseases to the emergence of novel peptide molecules targeting oncology, neurological disorders, and immune diseases, the landscape of peptide drug development continues to expand.  To better meet the evolving needs of global partners, WuXi AppTec has established an integrated solution for peptides and related chemical conjugates, covering key stages including custom synthesis, covalent conjugation, process development, and CMC, while also providing integrated bioanalytical solutions such as pharmacokinetic analysis and immunogenicity assessment. Together, these capabilities provide strong support for the discovery and development of peptides and complex peptide conjugate therapeutics. This article reviews major developments in peptide therapeutics worldwide during the first quarter of 2026, including regulatory approvals, clinical progress, and industry collaborations, while highlighting key technical challenges and emerging trends shaping this rapidly evolving field. Regulatory Developments In the first quarter of 2026, peptide therapeutics achieved several important regulatory milestones globally. Among them, GLP-1 therapies continued to make breakthroughs in obesity and related disease areas. Novo Nordisk’s high-dose semaglutide Wegovy HD (7.2 mg) injection received U.S. FDA approval this quarter for obesity patients who have tolerated the 2.4 mg dose for at least four weeks but still require additional weight reduction. Meanwhile, semaglutide (brand name Kayshild) received a recommendation for conditional approval from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) for the treatment of metabolic dysfunction-associated steatohepatitis (MASH) with liver fibrosis in patients without cirrhosis. The therapy is expected to receive formal approval in April this year. According to the company, Kayshild could become the first GLP-1 therapy approved by the EMA for a MASH indication. In addition, Health Canada approved the oral semaglutide tablet Rybelsus in January for reducing the risk of major adverse cardiovascular events (MACE)—including cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke—in adults with type 2 diabetes who have established cardiovascular disease or are at high cardiovascular risk. Beyond GLP-1 therapies, several peptide drugs also achieved key regulatory breakthroughs. Yuviwel (navepegritide; TransCon CNP) from Ascendis Pharma received accelerated approval from the U.S. FDA for the treatment of children aged two years and older with achondroplasia whose growth plates have not yet closed. According to the company, the drug is the first once-weekly treatment approved for this patient population. Also in March, oral peptide therapy Icotyde (icotrokinra) developed by Johnson & Johnson in collaboration with Protagonist Therapeutics received FDA approval as a first-line treatment for adults with moderate-to-severe plaque psoriasis (PsO), as well as pediatric patients aged 12 years and older weighing at least 40 kg who are eligible for systemic therapy or phototherapy. According to the press release, Icotyde is the first targeted oral peptide drug designed to selectively block the IL-23 receptor. Additionally, Rhythm Pharmaceuticals’ peptide drug Imcivree (setmelanotide) received FDA approval this quarter for an expanded indication to treat acquired hypothalamic obesity (HO) in adults and children aged four years and older, helping reduce excess body weight and maintain long-term weight loss. Meanwhile, the European Commission (EC) approved Aspaveli (pegcetacoplan) developed by Sobi and Apellis Pharmaceuticals for use in combination with renin-angiotensin system (RAS) inhibitors to treat adolescents aged 12–17 and adults with C3 glomerulopathy (C3G) or primary immune complex membranoproliferative glomerulonephritis (IC-MPGN). Clinical Progress In clinical development, GLP-1–related therapies remained one of the most active areas of peptide drug research this quarter, with several pharmaceutical companies reporting progress in obesity and metabolic disease treatments. Eli Lilly and Company announced positive Phase 3 results for its potential first-in-class triple hormone receptor agonist retatrutide, which simultaneously targets GLP-1, glucose-dependent insulinotropic polypeptide (GIP), and glucagon receptors. Analysis showed that after 40 weeks of once-weekly treatment, patients with type 2 diabetes experienced an average HbA1c reduction of 1.7%–2.0%, while patients in the highest-dose group achieved an average body-weight reduction of 16.8% (36.6 lbs). At the same time, Pfizer’s long-acting GLP-1 receptor agonist PF-08653944 (PF'3944, formerly MET-097i) demonstrated positive results in a Phase 2b trial. All four dosing regimens achieved significantly greater weight reduction from randomization to Week 28 compared with placebo (P<0.001). Notably, after transitioning to monthly dosing, weight-loss effects remained strong and sustained, with no plateau observed by Week 28, suggesting the therapy may support a once-monthly dosing regimen. Multiple Phase 3 trials of PF'3944 are currently underway. Additionally, Viking Therapeutics’ dual GIP/GLP-1 receptor agonist VK2735 reported Phase 2 results published in Obesity, while enrollment for its Phase 3 trial was completed this quarter. Altimmune’s candidate pemvidutide received FDA Breakthrough Therapy designation earlier this year for the treatment of MASH, and the company has reached agreement with the FDA on the key design of its Phase 3 registrational trial targeting patients with moderate-to-severe liver fibrosis. Meanwhile, Novo Nordisk reported that its fixed-dose combination therapy CagriSema outperformed semaglutide in Phase 3 trials in both weight reduction and HbA1c improvement. CagriSema combines the long-acting amylin analog cagrilintide (2.4 mg) with semaglutide (2.4 mg). Zealand Pharma and AbbVie also reported encouraging results this quarter for amylin-targeting therapies petrelintide and ABBV-295, with positive Phase 2 and Phase 1 results, respectively, for the treatment of obesity. Importantly, the application of GLP-1 therapies is expanding beyond metabolic diseases. This quarter, Eli Lilly reported that its GLP-1/GIP dual receptor agonist Zepbound (tirzepatide) combined with the IL-17A monoclonal antibody Taltz (ixekizumab) met primary endpoints in two Phase 3 trials targeting overweight or obese patients with moderate-to-severe plaque psoriasis and active psoriatic arthritis (PsA). These findings suggest that GLP-1 therapies may form new combination treatment strategies alongside psoriasis biologics. Beyond GLP-1–related therapies, several peptide drugs also advanced in other disease areas. For example, PRI-002, an oral peptide therapy from Priavoid targeting β-amyloid (Aβ) oligomers, demonstrated amyloid-related imaging abnormality (ARIA) rates comparable to the placebo group in previous Phase 3 studies. In addition, results from a Phase 1/2 study showed that a patient with both familial adenomatous polyposis (FAP) and associated desmoid tumors experienced significant improvement after 60 weeks of treatment with zolucatetide, a potential first-in-class peptide therapy developed by Parabilis Medicines. Compared with baseline, both the number and size of duodenal polyps were significantly reduced, with disease stage improving from Spigelman stage II to stage I, while the desmoid tumor diameter decreased by 52.2%. According to the company, zolucatetide is the first inhibitor designed to directly block the interaction between β-catenin and TCF. Partnerships and Financing On the industry collaboration front, several large pharmaceutical companies announced peptide-focused partnerships this quarter. In January, AstraZeneca and CSPC Pharmaceutical Group announced a strategic collaboration worth up to $3.5 billion to advance eight next-generation therapies targeting obesity and type 2 diabetes. The partners will initially advance four programs combining CSPC’s AI-driven peptide discovery platform with its proprietary LiquidGel once-monthly delivery technology. In February, Novartis entered into a collaboration with Unnatural Products (UNP) worth more than $1.7 billion to develop macrocyclic peptide therapeutics. In terms of financing, several emerging companies also secured strong investor support. Parabilis Medicines completed a Series F financing exceeding $300 million earlier this year to advance the development of zolucatetide. Meanwhile, Pinnacle Medicines completed $89 million Series B financing in March to accelerate the clinical development of its pipelines. WuXi AppTec Supports Innovation in Peptide Therapeutics As peptide therapeutics continue to expand into obesity, metabolic diseases, and a growing range of innovative indications, molecular designs are becoming increasingly sophisticated. From fatty-acid modification and PEGylation to protein fusion and peptide conjugation, many next-generation peptide drugs are engineered to achieve longer half-lives and improved therapeutic performance. However, these innovations also introduce new analytical challenges in drug development. Particularly during clinical studies, accurately characterizing the in vivo exposure profile and immunogenicity risks of peptide drugs, and understanding how structural modifications may influence these parameters, has become critical for advancing therapies into later-stage development. Against this backdrop, integrated bioanalytical capabilities supporting both pharmacokinetics (PK) and immunogenicity assessment are becoming increasingly essential. To help partners address these challenges, WuXi AppTec Bioanalytical Services (BAS), supported by a highly mature bioanalytical technology platform, has established a systematic analytical solution tailored to the development needs of next-generation peptide therapeutics. This integrated platform effectively addresses the complex challenges associated with pharmacokinetics (PK) and immunogenicity studies in clinical trials. As peptide drugs continue to increase in molecular weight, incorporate more structural modifications, and adopt increasingly complex conjugation formats, their bioanalysis presents a series of unique challenges. In LC–MS/MS analysis, peptides often exhibit broad charge state distributions and heterogeneous ionization efficiency, leading to signal dispersion and ion suppression that can compromise sensitivity and method robustness. Meanwhile, peptides typically possess limited epitopes and high homology to endogenous counterparts, resulting in low immunogenicity and challenges in generating highly specific antibodies, as well as increased susceptibility to endogenous interference and cross-reactivity in ligand-binding assays (LBA). In addition, structural modifications such as fatty acid conjugation, PEGylation, or protein fusion—while extending half-life—may introduce additional immunogenicity risks (e.g., anti-PEG antibodies), further complicating anti-drug antibody (ADA) and neutralizing antibody (NAb) assessments. To address these challenges, WuXi AppTec BAS integrates high-sensitivity LC–MS/MS, immunocapture–mass spectrometry, ELISA/MSD platforms, and cell-based functional assays to enable seamless support from PK analysis to comprehensive immunogenicity evaluation. Through optimized sample preparation strategies, implementation of immunocapture techniques, and adoption of bottom-up approaches such as trypsin digestion, the platform significantly enhances detection sensitivity and reduces matrix interference, ensuring robust and specific analysis of structurally complex and long-chain peptides. For immunogenicity assessment, a tiered evaluation framework is established, incorporating bridging ADA assays, confirmatory testing, and titer determination, alongside advanced strategies such as acid dissociation (ACE) and minimum required dilution (MRD) optimization to improve drug tolerance and assay sensitivity. In parallel, careful optimization of labeled reagents and assay conditions minimizes endogenous interference and non-specific binding, while cell-based NAb assays provide functional evaluation of neutralizing responses—enabling an end-to-end immunogenicity assessment workflow for complex peptide and peptide-conjugated therapeutics. WuXi AppTec BAS has successfully supported clinical PK and immunogenicity studies for a wide range of peptide therapeutics, including GLP-1 analogs and insulin analogs, delivering end-to-end capabilities from method development and validation to sample analysis. Enabled by standardized workflows and integrated multi-technology expertise, WuXi AppTec provides high-sensitivity, high-reliability bioanalytical support for peptide therapeutics, accelerating the advancement of innovative peptide drugs from research into clinical development. 参考资料：[1] 各公司官网 免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，聚焦全球生物医药健康创新