同行致遠 | 2025年多肽療法擴展至MASH與罕見病，迎來多線突破 | Bilingual

編者按：近年來，得益于代謝穩定性高、靶點親和力強及生物特異性優異等特性，多肽療法正迅速崛起為全球新藥開發的重要方向。截至目前，全球范圍內正在開展的多肽療法相關臨床試驗數量已超過630項，涵蓋包括代謝性疾病、腫瘤、免疫疾病等在內的廣泛適應癥，顯示出該領域的巨大活力與發展潛力。藥明康德旗下WuXi TIDES平臺圍繞多肽、寡核苷酸及其相關化學偶聯藥物建立了一體化解決方案，覆蓋定制合成、共價連接、工藝開發和CMC等關鍵環節，賦能創新項目加速進入臨床階段。本文將盤點2025年多肽產業的進展，并分享一則多肽療法的具體賦能案例，助您深入了解該領域的最新動態與未來方向。

臨床與監管進展

2025年，多肽療法在減重領域持續取得一系列重要臨床進展。禮來（Eli Lilly and Company）旗下葡萄糖依賴性促胰島素多肽（GIP）/GLP-1雙重受體激動劑Mounjaro（tirzepatide，替爾泊肽）在3期SURMOUNT-5研究中成功達到主要終點及全部五項關鍵次要終點。結果顯示，在第72周時，替爾泊肽治療組的平均體重減輕幅度達到20.2%，顯著高于活性對照藥物組的13.7%。而禮來的在研、每周一次皮下注射的選擇性長效胰淀素受體激動劑eloralintide（LY3841136）在一項2期試驗中則顯示，在第48周時，所有eloralintide治療組均達到主要終點，平均體重下降幅度介于9.5%至20.1%之間，而安慰劑組僅為0.4%。基于上述結果，禮來已于12月啟動eloralintide用于治療肥胖的3期臨床研究患者入組。

與此同時，禮來還在12月公布了其在研、每周一次、潛在“first-in-class”的GIP、GLP-1及胰高血糖素（glucagon）受體靶向三重激動劑retatrutide的最新研究數據。該研究在患有肥胖或超重且合并膝骨關節炎、但無糖尿病的成年人中開展，作為健康飲食和運動的輔助治療方案。結果顯示，接受12 mg retatrutide治療68周后，患者平均減重達28.7%；在試驗結束時，超過八分之一的患者已完全無膝部疼痛。

諾和諾德（Novo Nordisk）也在減重領域持續進展。11月底，公司宣布已向美國FDA提交7.2 mg Wegovy（semaglutide，司美格魯肽）注射劑的補充新藥申請（sNDA），擬用于聯合低熱量飲食和增加體力活動，幫助肥胖成人實現長期體重管理。12月，諾和諾德進一步向美國FDA遞交了CagriSema的新藥申請（NDA）。該療法擬與減少熱量飲食及增加體力活動聯合，用于伴有至少一種體重相關共病的肥胖或超重成人患者，以實現減重并長期維持體重管理效果。CagriSema是一款由長效胰淀素類似物cagrilintide（2.4 mg）與司美格魯肽（2.4 mg）組成的固定劑量聯合療法，設計為每周一次皮下注射。

除減重領域外，多肽類藥物在其他疾病適應癥方面亦持續取得突破性進展。今年8月，美國FDA加速批準Wegovy（2.4 mg司美格魯肽）用于聯合低熱量飲食和增加體力活動，治療伴有中度至重度肝纖維化（2期或3期）的非肝硬化型代謝功能障礙相關脂肪性肝炎（MASH）成人患者。根據新聞稿，Wegovy成為首個獲批用于治療MASH的GLP-1療法。10月，FDA進一步批準Rybelsus（口服司美格魯肽）的一項新適應癥，用于降低2型糖尿病高風險成人患者發生重大不良心血管事件（MACE，包括心血管死亡、心臟病發作或中風）的風險，無論患者是否具有既往心血管事件史。

與此同時，替爾泊肽在3期臨床中亦顯示在降低主要不良心血管事件風險方面不劣于GLP-1受體激動劑Trulicity（dulaglutide），而后者已在REWIND研究中證實具有明確的心血管獲益。此外，默沙東（MSD）也于9月宣布，其在研口服大環肽enlicitide decanoate在3期試驗中能夠顯著降低高膽固醇血癥患者的低密度脂蛋白膽固醇（LDL-C）水平。

在免疫疾病領域，強生（Johnson & Johnson）與Protagonist Therapeutics已向美國FDA遞交新藥申請，尋求批準其聯合開發的口服多肽療法icotrokinra，用于治療12歲及以上中度至重度斑塊狀銀屑病（PsO）的成人及兒科患者。在腫瘤領域，PDS Biotechnology旗下多肽癌癥疫苗PDS0101（Versamune HPV）聯合PD-1抑制劑Keytruda（pembrolizumab）在2期臨床試驗中，作為一線治療方案時，患者的中位總生存期達到39.3個月。相比之下，同類患者在接受標準治療聯合化療時的最佳中位總生存期為17.9個月。此外，FDA亦于11月底受理ITM Isotope Technologies遞交的n.c.a. 177Lu-edotreotide新藥申請。該候選藥物為ITM自主研發的合成靶向放射性治療藥物，擬用于治療胃腸胰神經內分泌腫瘤（GEP-NETs）。

在罕見病領域，多肽療法同樣取得多項關鍵突破。今年7月，美國FDA批準Apellis Pharmaceuticals旗下雙環肽療法Empaveli（pegcetacoplan）擴展適應癥，用于治療C3腎小球病（C3G）及原發性免疫復合物膜增生性腎小球腎炎（IC-MPGN），以減少患者蛋白尿。9月，Stealth BioTherapeutics開發的Forzinity（elamipretide）亦迎來FDA批準，成為巴思綜合征全球首款獲批療法。

研發合作與融資進展

羅氏（Roche）與Zealand Pharma在3月就petrelintide簽署了一項潛在數十億美元規模的全球合作及許可協議，進一步強化其在多肽類代謝藥物領域的戰略布局。阿斯利康（AstraZeneca）則與專注于口服大環肽藥物開發的元思生肽（Syneron Bio）達成總金額高達34億美元的戰略合作。根據協議，阿斯利康將獲得其智能化高通量大環肽研發平臺Synova的使用權，雙方將共同推進針對罕見病、自身免疫及代謝性慢性疾病的潛在“first-in-class”大環肽療法開發。

與此同時，諾和諾德以最高20億美元的交易總額，獲得聯邦制藥（United Laboratories）旗下GLP-1R/GIPR/GCGR三重受體激動劑UBT251的全球權益，相關適應癥覆蓋肥胖癥、2型糖尿病及多種代謝性疾病。4月，默沙東亦宣布與Cyprumed達成一項近5億美元的合作協議，雙方將基于Cyprumed的創新口服藥物遞送技術，共同開發默沙東旗下的口服多肽候選藥物。

并購層面，輝瑞（Pfizer）于9月宣布與Metsera達成總額達數十億美元的收購協議。通過此次交易，輝瑞將獲得Metsera旗下具備差異化優勢的口服及注射型腸促胰島素和胰淀素類候選藥物及其聯合療法組合，這些項目在有效性與安全性方面被認為具有“best-in-class”潛力，有望進一步鞏固輝瑞在代謝疾病領域的布局。整體來看，這些合作不僅反映出大型藥企對多肽療法的高度重視，也表明其應用邊界正不斷向更廣泛的疾病領域延伸。

▲2025年多肽藥物領域>5000萬美元部分投融資信息

回望2025年，多肽療法在減重與代謝疾病領域的臨床驗證、監管推進和商業合作持續加速推進；與此同時，其應用邊界也在不斷拓展，逐步延伸至心血管、免疫、腫瘤及罕見病等更廣闊的治療場景。展望未來，隨著研發效率進一步提升、全球協作持續深化，多肽療法有望在更多適應癥中釋放更大臨床價值，為不同患者帶來更豐富、更有效的治療選擇。

一體化平臺賦能多肽偶聯藥物開發

藥明康德旗下WuXi TIDES搭建了獨特的CRDMO平臺，為全球合作伙伴開發寡核苷酸、多肽藥物及相關化學偶聯物（TIDES藥物）提供高效、靈活和高質量解決方案。WuXi TIDES的一體化平臺讓多個團隊能夠并行攻關，密切合作，顯著提高項目推進速度。下面的這個案例將展示這一平臺如何助力合作伙伴，加速一款環肽-GalNAc偶聯藥物的研發進程。

在該案例中，合作伙伴的目標是將一款處于發現階段的環肽-GalNAc偶聯藥物推進至IND申請。然而，這一過程面臨多重挑戰：由于藥物分子結構復雜，并且合成過程中一個關鍵多肽中間產物溶解度很低，導致整體產率偏低。同時，合作伙伴以產品的最終商業化為核心目標，這也意味著在早期開發中，如何開發具有成本效益的生產工藝成為首要任務之一。

針對這些挑戰，WuXi TIDES的原料藥和制劑與分析團隊緊密協作，開展聯合攻關。首先要解決的是總產率偏低的問題。研發團隊利用WuXi TIDES內部的GalNAc合成能力，采取了一系列質量控制措施，成功解決了GalNAc原料中的關鍵性雜質問題。團隊通過添加合適的配體等舉措，為提高關鍵多肽中間產物的溶解度奠定了堅實基礎。通過對合成步驟的多重優化，團隊將總產率從發現階段的10%提高至20%，提升幅度高達100%。憑借多個團隊的高效協作，WuXi TIDES僅用12個月便順利將該藥物推進至IND申報階段。客戶對產率的顯著提升非常滿意，并決定繼續與WuXi TIDES團隊進行GMP生產合作。

在確保順利推進的同時，WuXi TIDES團隊還致力于降低藥物生產成本。他們對環肽-GalNAc偶聯藥物的生產和純化流程進行了系統性優化。通過替換昂貴的原材料，使原材料成本降低8%；將關鍵中間產物的生產步驟由8步縮減為7步，使整體生產成本再降低10%；并利用多柱逆流溶劑梯度純化（MCSGP）技術，在縮短生產周期的同時進一步降低了成本。最終，憑借這一系列持續優化措施，與早期的1公斤GLP批次相比，生產8公斤GMP批次時，每公斤的成本降低了71%。

未來，WuXi TIDES將繼續依托其一體化、端到端的CRDMO平臺，支持合作伙伴推進多肽藥物研發，助力前沿科技轉化為惠及全球患者的突破性療法。

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.

參考資料：

[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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