编者按：近年来，得益于代谢稳定性高、靶点亲和力强及生物特异性优异等特性，多肽疗法正迅速崛起为全球新药开发的重要方向。截至目前，全球范围内正在开展的多肽疗法相关临床试验数量已超过630项，涵盖包括代谢性疾病、肿瘤、免疫疾病等在内的广泛适应症，显示出该领域的巨大活力与发展潜力。药明康德旗下WuXi TIDES平台围绕多肽、寡核苷酸及其相关化学偶联药物建立了一体化解决方案，覆盖定制合成、共价连接、工艺开发和CMC等关键环节，赋能创新项目加速进入临床阶段。本文将盘点2025年多肽产业的进展，并分享一则多肽疗法的具体赋能案例，助您深入了解该领域的最新动态与未来方向。
临床与监管进展
2025年，多肽疗法在减重领域持续取得一系列重要临床进展。礼来（Eli Lilly and Company）旗下葡萄糖依赖性促胰岛素多肽（GIP）/GLP-1双重受体激动剂Mounjaro（tirzepatide，替尔泊肽）在3期SURMOUNT-5研究中成功达到主要终点及全部五项关键次要终点。结果显示，在第72周时，替尔泊肽治疗组的平均体重减轻幅度达到20.2%，显著高于活性对照药物组的13.7%。而礼来的在研、每周一次皮下注射的选择性长效胰淀素受体激动剂eloralintide（LY3841136）在一项2期试验中则显示，在第48周时，所有eloralintide治疗组均达到主要终点，平均体重下降幅度介于9.5%至20.1%之间，而安慰剂组仅为0.4%。基于上述结果，礼来已于12月启动eloralintide用于治疗肥胖的3期临床研究患者入组。
与此同时，礼来还在12月公布了其在研、每周一次、潜在“first-in-class”的GIP、GLP-1及胰高血糖素（glucagon）受体靶向三重激动剂retatrutide的最新研究数据。该研究在患有肥胖或超重且合并膝骨关节炎、但无糖尿病的成年人中开展，作为健康饮食和运动的辅助治疗方案。结果显示，接受12 mg retatrutide治疗68周后，患者平均减重达28.7%；在试验结束时，超过八分之一的患者已完全无膝部疼痛。
诺和诺德（Novo Nordisk）也在减重领域持续进展。11月底，公司宣布已向美国FDA提交7.2 mg Wegovy（semaglutide，司美格鲁肽）注射剂的补充新药申请（sNDA），拟用于联合低热量饮食和增加体力活动，帮助肥胖成人实现长期体重管理。12月，诺和诺德进一步向美国FDA递交了CagriSema的新药申请（NDA）。该疗法拟与减少热量饮食及增加体力活动联合，用于伴有至少一种体重相关共病的肥胖或超重成人患者，以实现减重并长期维持体重管理效果。CagriSema是一款由长效胰淀素类似物cagrilintide（2.4 mg）与司美格鲁肽（2.4 mg）组成的固定剂量联合疗法，设计为每周一次皮下注射。
除减重领域外，多肽类药物在其他疾病适应症方面亦持续取得突破性进展。今年8月，美国FDA加速批准Wegovy（2.4 mg司美格鲁肽）用于联合低热量饮食和增加体力活动，治疗伴有中度至重度肝纤维化（2期或3期）的非肝硬化型代谢功能障碍相关脂肪性肝炎（MASH）成人患者。根据新闻稿，Wegovy成为首个获批用于治疗MASH的GLP-1疗法。10月，FDA进一步批准Rybelsus（口服司美格鲁肽）的一项新适应症，用于降低2型糖尿病高风险成人患者发生重大不良心血管事件（MACE，包括心血管死亡、心脏病发作或中风）的风险，无论患者是否具有既往心血管事件史。
与此同时，替尔泊肽在3期临床中亦显示在降低主要不良心血管事件风险方面不劣于GLP-1受体激动剂Trulicity（dulaglutide），而后者已在REWIND研究中证实具有明确的心血管获益。此外，默沙东（MSD）也于9月宣布，其在研口服大环肽enlicitide decanoate在3期试验中能够显著降低高胆固醇血症患者的低密度脂蛋白胆固醇（LDL-C）水平。
在免疫疾病领域，强生（Johnson & Johnson）与Protagonist Therapeutics已向美国FDA递交新药申请，寻求批准其联合开发的口服多肽疗法icotrokinra，用于治疗12岁及以上中度至重度斑块状银屑病（PsO）的成人及儿科患者。在肿瘤领域，PDS Biotechnology旗下多肽癌症疫苗PDS0101（Versamune HPV）联合PD-1抑制剂Keytruda（pembrolizumab）在2期临床试验中，作为一线治疗方案时，患者的中位总生存期达到39.3个月。相比之下，同类患者在接受标准治疗联合化疗时的最佳中位总生存期为17.9个月。此外，FDA亦于11月底受理ITM Isotope Technologies递交的n.c.a. 177Lu-edotreotide新药申请。该候选药物为ITM自主研发的合成靶向放射性治疗药物，拟用于治疗胃肠胰神经内分泌肿瘤（GEP-NETs）。
在罕见病领域，多肽疗法同样取得多项关键突破。今年7月，美国FDA批准Apellis Pharmaceuticals旗下双环肽疗法Empaveli（pegcetacoplan）扩展适应症，用于治疗C3肾小球病（C3G）及原发性免疫复合物膜增生性肾小球肾炎（IC-MPGN），以减少患者蛋白尿。9月，Stealth BioTherapeutics开发的Forzinity（elamipretide）亦迎来FDA批准，成为巴思综合征全球首款获批疗法。
研发合作与融资进展
罗氏（Roche）与Zealand Pharma在3月就petrelintide签署了一项潜在数十亿美元规模的全球合作及许可协议，进一步强化其在多肽类代谢药物领域的战略布局。阿斯利康（AstraZeneca）则与专注于口服大环肽药物开发的元思生肽（Syneron Bio）达成总金额高达34亿美元的战略合作。根据协议，阿斯利康将获得其智能化高通量大环肽研发平台Synova的使用权，双方将共同推进针对罕见病、自身免疫及代谢性慢性疾病的潜在“first-in-class”大环肽疗法开发。
与此同时，诺和诺德以最高20亿美元的交易总额，获得联邦制药（United Laboratories）旗下GLP-1R/GIPR/GCGR三重受体激动剂UBT251的全球权益，相关适应症覆盖肥胖症、2型糖尿病及多种代谢性疾病。4月，默沙东亦宣布与Cyprumed达成一项近5亿美元的合作协议，双方将基于Cyprumed的创新口服药物递送技术，共同开发默沙东旗下的口服多肽候选药物。
并购层面，辉瑞（Pfizer）于9月宣布与Metsera达成总额达数十亿美元的收购协议。通过此次交易，辉瑞将获得Metsera旗下具备差异化优势的口服及注射型肠促胰岛素和胰淀素类候选药物及其联合疗法组合，这些项目在有效性与安全性方面被认为具有“best-in-class”潜力，有望进一步巩固辉瑞在代谢疾病领域的布局。整体来看，这些合作不仅反映出大型药企对多肽疗法的高度重视，也表明其应用边界正不断向更广泛的疾病领域延伸。
▲2025年多肽药物领域>5000万美元部分投融资信息
回望2025年，多肽疗法在减重与代谢疾病领域的临床验证、监管推进和商业合作持续加速推进；与此同时，其应用边界也在不断拓展，逐步延伸至心血管、免疫、肿瘤及罕见病等更广阔的治疗场景。展望未来，随着研发效率进一步提升、全球协作持续深化，多肽疗法有望在更多适应症中释放更大临床价值，为不同患者带来更丰富、更有效的治疗选择。
一体化平台赋能多肽偶联药物开发
药明康德旗下WuXi TIDES搭建了独特的CRDMO平台，为全球合作伙伴开发寡核苷酸、多肽药物及相关化学偶联物（TIDES药物）提供高效、灵活和高质量解决方案。WuXi TIDES的一体化平台让多个团队能够并行攻关，密切合作，显著提高项目推进速度。下面的这个案例将展示这一平台如何助力合作伙伴，加速一款环肽-GalNAc偶联药物的研发进程。
在该案例中，合作伙伴的目标是将一款处于发现阶段的环肽-GalNAc偶联药物推进至IND申请。然而，这一过程面临多重挑战：由于药物分子结构复杂，并且合成过程中一个关键多肽中间产物溶解度很低，导致整体产率偏低。同时，合作伙伴以产品的最终商业化为核心目标，这也意味着在早期开发中，如何开发具有成本效益的生产工艺成为首要任务之一。
针对这些挑战，WuXi TIDES的原料药和制剂与分析团队紧密协作，开展联合攻关。首先要解决的是总产率偏低的问题。研发团队利用WuXi TIDES内部的GalNAc合成能力，采取了一系列质量控制措施，成功解决了GalNAc原料中的关键性杂质问题。团队通过添加合适的配体等举措，为提高关键多肽中间产物的溶解度奠定了坚实基础。通过对合成步骤的多重优化，团队将总产率从发现阶段的10%提高至20%，提升幅度高达100%。凭借多个团队的高效协作，WuXi TIDES仅用12个月便顺利将该药物推进至IND申报阶段。客户对产率的显著提升非常满意，并决定继续与WuXi TIDES团队进行GMP生产合作。
在确保顺利推进的同时，WuXi TIDES团队还致力于降低药物生产成本。他们对环肽-GalNAc偶联药物的生产和纯化流程进行了系统性优化。通过替换昂贵的原材料，使原材料成本降低8%；将关键中间产物的生产步骤由8步缩减为7步，使整体生产成本再降低10%；并利用多柱逆流溶剂梯度纯化（MCSGP）技术，在缩短生产周期的同时进一步降低了成本。最终，凭借这一系列持续优化措施，与早期的1公斤GLP批次相比，生产8公斤GMP批次时，每公斤的成本降低了71%。
未来，WuXi TIDES将继续依托其一体化、端到端的CRDMO平台，支持合作伙伴推进多肽药物研发，助力前沿科技转化为惠及全球患者的突破性疗法。
Beyond Weight Loss: Peptide Therapeutics Break Through in Various Diseases in 2025
Peptide therapeutics have rapidly emerged as a vital focus in global drug development, driven by their enhanced metabolic stability, strong target affinity, and superior biological specificity. Currently, more than 630 clinical trials involving peptide therapies are underway worldwide, covering a broad spectrum of indications—including metabolic diseases, cancer, and immune disorders—underscoring the field’s strong momentum and promising outlook. To support partners in efficiently advancing these innovative therapies from discovery to clinic, WuXi TIDES offers efficient, flexible, and high-quality solutions for the drug development of oligonucleotides, peptides and related synthetic conjugates (“TIDES” drugs). Here we summarize major trends in the peptide therapeutics field during 2025 and highlights a case study that showcases WuXi TIDES’ role in driving progress in this area.
Clinical and Regulatory Progress
In 2025, peptide therapies continued to deliver a series of important clinical advances in the weight management space. Eli Lilly and Company’s dual GIP/GLP-1 receptor agonist Mounjaro (tirzepatide) successfully met the primary endpoint as well as all five key secondary endpoints in the Phase 3 SURMOUNT-5 study. Results showed that at Week 72, patients treated with tirzepatide achieved a mean weight reduction of 20.2%, significantly exceeding the 13.7% observed in the active comparator group.
Meanwhile, Lilly’s investigational, once-weekly, subcutaneous selective long-acting amylin receptor agonist eloralintide demonstrated positive results in a Phase 2 trial. At Week 48, all eloralintide treatment groups met the primary endpoint, with mean weight reductions ranging from 9.5% to 20.1%, compared with just 0.4% in the placebo group. Based on these results, Lilly initiated patient enrollment in a Phase 3 clinical program of eloralintide for obesity treatment in December.
Also in December, Lilly reported new data for its investigational, once-weekly, potentially first-in-class GIP, GLP-1 and glucagon triple hormone receptor agonist retatrutide. The study was conducted in adults with obesity or overweight and concomitant knee osteoarthritis, without diabetes, as an adjunct to a healthy diet and exercise. Results showed that after 68 weeks of treatment with 12 mg retatrutide, patients achieved a mean weight reduction of 28.7%; more than one-eighth of patients treated with retatrutide reported free from knee pain at the end of the trial.
Novo Nordisk also continued to advance in its weight management therapies. In late November, the company announced the submission of a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for a 7.2 mg dose of Wegovy (semaglutide), intended for use in combination with a reduced-calorie diet and increased physical activity to support long-term weight management in adults with obesity.
In December, Novo Nordisk submitted an New Drug Application (NDA) to the FDA for CagriSema, which is intended to be used alongside reduced-calorie diet and increased physical activity for weight reduction and long-term weight maintenance in adults with obesity or overweight and at least one weight-related comorbidity. CagriSema is a fixed-dose combination of the long-acting amylin analogue cagrilintide (2.4 mg) and semaglutide (2.4 mg), designed for once-weekly subcutaneous administration.
Beyond weight management, peptide therapeutics continued to achieve breakthroughs across other disease indications. In August, the FDA granted accelerated approval to Wegovy (2.4 mg semaglutide), in combination with a reduced-calorie diet and increased physical activity, for the treatment of adults with non-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH) and moderate to advanced liver fibrosis (Stage 2 or 3). According to the company, Wegovy became the first GLP-1 therapy approved for the treatment of MASH. In October, the FDA further approved a new indication for Rybelsus (oral semaglutide) to reduce the risk of major adverse cardiovascular events (MACE, including cardiovascular death, myocardial infarction, or stroke) in adults with type 2 diabetes at high cardiovascular risk, regardless of prior cardiovascular event history.
In parallel, Phase 3 clinical data showed that tirzepatide was non-inferior to the GLP-1 receptor agonist Trulicity (dulaglutide) in reducing the risk of major adverse cardiovascular events; Trulicity has previously demonstrated clear cardiovascular benefit in the REWIND trial. In addition, MSD announced in September that its investigational oral macrocyclic peptide enlicitide decanoate significantly reduced low-density lipoprotein cholesterol (LDL-C) levels in patients with hypercholesterolemia in a Phase 3 trial.
In immunology, Johnson & Johnson and Protagonist Therapeutics submitted a NDA to the FDA seeking approval of their jointly developed oral peptide therapy icotrokinra for the treatment of adults and pediatric patients aged 12 years and older with moderate to severe plaque psoriasis (PsO). In oncology, PDS Biotechnology’s peptide-based cancer vaccine PDS0101 (Versamune HPV), in combination with the PD-1 inhibitor Keytruda (pembrolizumab), achieved a median overall survival of 39.3 months when used as a first-line treatment in a Phase 2 clinical trial. By comparison, the best reported median overall survival for similar patients receiving standard-of-care therapy combined with chemotherapy is 17.9 months. In addition, the FDA accepted an NDA submitted by ITM Isotope Technologies in late November for n.c.a. 177Lu-edotreotide, an investigational synthetic targeted radiotherapeutic developed by ITM for the treatment of gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
In the rare disease arena, peptide therapeutics also delivered several pivotal milestones. In July, the FDA approved an expanded indication for Empaveli (pegcetacoplan), a bicircular peptide therapy from Apellis Pharmaceuticals, for the treatment of C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN) to reduce proteinuria. In September, Stealth BioTherapeutics’ Forzinity (elamipretide) also received FDA approval, becoming the first approved therapy globally for Barth syndrome.
R&D Collaboration & Financing Progress
In March, Roche and Zealand Pharma entered into a global collaboration and licensing agreement for petrelintide, with a potential total value of several billion dollars, further strengthening Roche’s capability in peptide-based metabolic therapies. AstraZeneca also announced a strategic collaboration valued at up to $3.4 billion with Syneron Bio, a company focused on oral macrocyclic peptide drug development. Under the agreement, AstraZeneca will gain access to Syneron Bio’s intelligent high-throughput macrocyclic peptide discovery platform, Synova, and the two parties will jointly advance the development of potentially first-in-class macrocyclic peptide therapies targeting rare diseases, autoimmune disorders, and metabolic chronic conditions.
At the same time, Novo Nordisk secured global rights to UBT251, a GLP-1R/GIPR/GCGR triple receptor agonist from United Laboratories, in a transaction valued at up to $2 billion, covering indications including obesity, type 2 diabetes, and other metabolic diseases. In April, MSD also announced a collaboration with Cyprumed valued at nearly $500 million, leveraging Cyprumed’s innovative oral drug delivery technology to co-develop MSD’s oral peptide candidates. Collectively, these partnerships underscore the strong commitment of large pharmaceutical companies to peptide therapeutics and highlight the continued expansion of their application into a broader range of disease areas.
On the M&A front, Pfizer announced in September a multi-billion-dollar acquisition agreement with Metsera. Through this transaction, Pfizer will gain access to Metsera’s differentiated portfolio of oral and injectable incretin- and amylin-based candidates and combination therapies, which are considered to have best-in-class potential in terms of efficacy and safety, further strengthening Pfizer’s long-term competitiveness in the metabolic disease space.
Looking back at 2025, peptide therapies saw accelerated momentum across clinical validation, regulatory advancement, and commercial collaboration in weight management and metabolic diseases, while their application boundaries continued to expand into cardiovascular, immunology, oncology, and rare diseases. Looking ahead, with further gains in R&D efficiency and deepening global collaboration, peptide therapies are well positioned to unlock greater clinical value across a wider range of indications, offering more diverse and effective treatment options for patients worldwide.
Integrated Platform Empowering Peptide Conjugate Development
WuXi TIDES, a specialized CRDMO platform under WuXi AppTec, provides efficient, flexible, and high-quality solutions for the development of oligonucleotides, peptides, and related chemically conjugated molecules—collectively known as "TIDES" drugs. The platform’s integrated nature enables cross-functional teams to collaborate in parallel, significantly accelerating project timelines. The following case study illustrates how WuXi TIDES’ integrated platform enables partners to accelerate the development of a peptide-GalNAc conjugate therapy.
In this project, the partner’s goal was to advance a peptide-GalNAc conjugate drug candidate, still at the discovery stage, toward an IND submission. The program, however, faced several challenges. The molecular structure of the candidate was highly complex, and a critical peptide intermediate in the synthesis process exhibited very poor solubility, leading to low overall yield. At the same time, because the partner prioritized eventual commercialization, establishing a cost-effective manufacturing process became a central objective in early development.
To address these obstacles, WuXi TIDES’ API, Drug Product and Analytical teams worked in close collaboration. The most urgent issue was the low overall yield. By leveraging WuXi TIDES’ in-house GalNAc synthesis capabilities, the R&D team implemented a series of quality control measures that resolved critical impurity issues in the GalNAc raw material. The team improved the poor solubility of a key peptide intermediate by directly using fractions and adding ligands. Through multiple rounds of process optimization, they not only enhanced the solubility of the key peptide intermediate but also doubled the overall yield, from 10% at the discovery stage to 20%. Thanks to efficient cross-team collaboration, WuXi TIDES advanced the program to the IND submission stage within just 12 months. The client, highly satisfied with the improved yield, chose to continue working with the WuXi TIDES team on GMP manufacturing.
In parallel with improving yield, the WuXi TIDES team also focused on reducing manufacturing costs. They conducted systematic optimization of the production and purification processes for the peptide-GalNAc conjugate. Replacing costly raw materials reduced material costs by 8%. Streamlining the production steps of a key intermediate from eight steps to seven further lowered overall costs by 10%. In addition, adopting multi-column counter-current solvent gradient purification (MCSGP) technology not only shortened the production cycle but also reduced costs further. Ultimately, this series of continuous optimizations enabled the team to reduce the cost per kilogram by 71% for an 8 kg GMP batch compared to the earlier 1 kg GLP batch.
Looking ahead, WuXi TIDES will continue to leverage its fully integrated, end-to-end CRDMO platform to support partners in advancing diverse classes of peptide therapeutics—ultimately helping to transform scientific breakthroughs into life-changing therapies for patients worldwide.
参考资料：
[1] Lilly's triple agonist, retatrutide, delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful Phase 3 trial. Retrieved December 11, 2025 from https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-weight-loss-average
[2] Peptide Synthesis Market Research 2025-2035: Over 75 Firms Now Offer Peptide Therapeutics API Manufacturing Services Globally - Peptide API Manufacturing Market Remains Fragmented Yet Competitive. Retrieved June 20, 2025 from https://www.globenewswire.com/news-release/2025/04/01/3053235/28124/en/Peptide-Synthesis-Market-Research-2025-2035-Over-75-Firms-Now-Offer-Peptide-Therapeutics-API-Manufacturing-Services-Globally-Peptide-API-Manufacturing-Market-Remains-Fragmented-Yet.html?utm_source=chatgpt.com
[3] Zealand Pharma announces completion of enrollment in the Phase 2b ZUPREME-1 trial of petrelintide in people with overweight or obesity. Retrieved June 19, 2025 from https://www.globenewswire.com/news-release/2025/03/17/3043399/0/en/Zealand-Pharma-announces-completion-of-enrollment-in-the-Phase-2b-ZUPREME-1-trial-of-petrelintide-in-people-with-overweight-or-obesity.html
[4] Novo Nordisk files for FDA approval of CagriSema, the first once-weekly combination of GLP 1 and amylin analogues for weight management. Retrieved December 18, 2025 from https://www.prnewswire.com/news-releases/novo-nordisk-files-for-fda-approval-of-cagrisema-the-first-once-weekly-combination-of-glp1-and-amylin-analogues-for-weight-management-302645868.html
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