編者按：近年來(lái)，憑借代謝穩(wěn)定性高、靶點(diǎn)親和力強(qiáng)以及生物特異性?xún)?yōu)異等優(yōu)勢(shì)，多肽療法正迅速崛起為全球新藥研發(fā)的重要方向。從GLP-1類(lèi)代謝疾病療法持續(xù)取得突破，到腫瘤、神經(jīng)系統(tǒng)疾病及免疫疾病等領(lǐng)域不斷涌現(xiàn)的新型多肽分子，多肽藥物的研發(fā)版圖正在不斷拓展。為了更好地滿(mǎn)足全球合作伙伴的研發(fā)需求，藥明康德圍繞多肽及其相關(guān)化學(xué)偶聯(lián)藥物構(gòu)建了一體化解決方案，覆蓋定制合成、共價(jià)連接、工藝開(kāi)發(fā)以及CMC等關(guān)鍵環(huán)節(jié)，并提供藥代動(dòng)力學(xué)分析和免疫原性檢測(cè)等整合生物分析解決方案，為發(fā)現(xiàn)和開(kāi)發(fā)多肽及復(fù)雜多肽偶聯(lián)藥物提供有力支持。本文將盤(pán)點(diǎn)2026年第一季度全球多肽療法在監(jiān)管審批、臨床研究以及產(chǎn)業(yè)合作等方面的重要進(jìn)展，并結(jié)合相關(guān)技術(shù)挑戰(zhàn)，帶您了解這一快速發(fā)展領(lǐng)域的最新動(dòng)態(tài)與趨勢(shì)。

監(jiān)管進(jìn)展

2026年第一季度，多肽療法在全球范圍內(nèi)迎來(lái)多項(xiàng)重要監(jiān)管進(jìn)展。其中，GLP-1類(lèi)療法繼續(xù)在肥胖及相關(guān)疾病領(lǐng)域取得突破。諾和諾德（Novo Nordisk）高劑量司美格魯肽Wegovy HD（7.2 mg）注射劑在本季度獲得美國(guó)FDA批準(zhǔn)，用于已耐受2.4 mg劑量治療至少4周、且仍需進(jìn)一步減重的肥胖患者。與此同時(shí)，司美格魯肽（商品名Kayshild）獲得歐洲藥品管理局（EMA）人用藥品委員會(huì)（CHMP）推薦有條件批準(zhǔn)，用于治療伴有肝纖維化的非肝硬化性代謝功能障礙相關(guān)脂肪性肝炎（MASH），預(yù)計(jì)將在今年4月正式獲批。根據(jù)新聞稿介紹，Kayshild有望成為首個(gè)獲EMA批準(zhǔn)用于MASH適應(yīng)癥的GLP-1類(lèi)藥物。

此外，加拿大衛(wèi)生部（Health Canada）在今年1月批準(zhǔn)司美格魯肽口服片劑（商品名Rybelsus），用于降低患有2型糖尿病且已確診心血管疾病或具有高心血管風(fēng)險(xiǎn)的成人患者發(fā)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）的風(fēng)險(xiǎn)。

在非GLP-1類(lèi)療法方面，多款多肽藥物也取得關(guān)鍵監(jiān)管突破。Ascendis Pharma旗下Yuviwel（navepegritide；TransCon CNP）獲得美國(guó)FDA加速批準(zhǔn)，用于治療2歲及以上且骨骺尚未閉合的軟骨發(fā)育不全兒童。根據(jù)公司新聞稿，該藥物為首個(gè)獲批用于該患者人群、且每周一次給藥的治療方案。

同樣在3月，強(qiáng)生（Johnson & Johnson）與Protagonist Therapeutics公司聯(lián)合開(kāi)發(fā)的口服多肽療法Icotyde（icotrokinra）獲得FDA批準(zhǔn)，用于一線(xiàn)治療中重度斑塊狀銀屑�。≒sO）成人患者，以及12歲及以上、體重至少40 kg且適合接受全身治療或光療的兒童患者。根據(jù)新聞稿，Icotyde是首個(gè)能夠精準(zhǔn)阻斷IL-23受體的靶向口服多肽藥物。

此外，Rhythm Pharmaceuticals旗下多肽藥物Imcivree（setmelanotide）的擴(kuò)展適應(yīng)癥也在本季度獲得FDA批準(zhǔn)，用于治療成人及4歲及以上兒童獲得性下丘腦性肥胖（HO），以降低過(guò)多體重并長(zhǎng)期維持減重效果。同樣值得關(guān)注的是，歐盟委員會(huì)（EC）批準(zhǔn)Sobi與Apellis Pharmaceuticals聯(lián)合開(kāi)發(fā)的Aspaveli（pegcetacoplan），用于與腎素-血管緊張素系統(tǒng)（RAS）抑制劑聯(lián)合治療12至17歲青少年及成人C3腎小球病（C3G）或原發(fā)性免疫復(fù)合物型膜增生性腎小球腎炎（IC-MPGN）。

臨床進(jìn)展

在臨床研究方面，GLP-1相關(guān)療法仍是本季度多肽研發(fā)最活躍的領(lǐng)域之一，多家藥企在肥胖及代謝疾病治療方向持續(xù)取得進(jìn)展。禮來(lái)（Eli Lilly and Company）宣布，其潛在“first-in-class”三重激素受體激動(dòng)劑retatrutide在3期試驗(yàn)中取得積極結(jié)果。該分子可同時(shí)靶向葡萄糖依賴(lài)性促胰島素多肽（GIP）、胰高血糖素樣肽-1（GLP-1）以及胰高血糖素受體。研究分析顯示，2型糖尿病患者在接受每周一次retatrutide治療40周后，糖化血紅蛋白（A1C）平均下降1.7–2.0個(gè)百分點(diǎn)，而最高劑量組患者的平均體重下降達(dá)到16.8%（36.6磅）。

與此同時(shí)，輝瑞（Pfizer）的長(zhǎng)效GLP-1受體激動(dòng)劑PF-08653944（PF'3944，曾用名MET-097i）也在2b期試驗(yàn)中取得積極結(jié)果。研究顯示，所有四種劑量方案在主要終點(diǎn)——從隨機(jī)分組至第28周的體重降低——方面均顯著優(yōu)于安慰劑（P<0.001）。值得關(guān)注的是，在切換至每月給藥后，減重效果依然強(qiáng)勁且持續(xù)，在第28周尚未出現(xiàn)平臺(tái)期，提示該療法具備每月一次給藥的潛力。目前，PF'3944的多項(xiàng)3期試驗(yàn)正在推進(jìn)中。

此外，Viking Therapeutics旗下GIP/GLP-1雙重受體激動(dòng)劑VK2735的2期試驗(yàn)結(jié)果發(fā)表于《肥胖》期刊，其3期試驗(yàn)也在本季度完成患者招募。Altimmune旗下候選藥物pemvidutide則在今年年初獲得FDA突破性療法認(rèn)定，用于治療MASH。公司已與FDA就3期注冊(cè)試驗(yàn)關(guān)鍵設(shè)計(jì)達(dá)成一致，即將啟動(dòng)針對(duì)中至重度肝纖維化MASH患者的3期研究。

與此同時(shí)，諾和諾德宣布其固定劑量聯(lián)合療法CagriSema在3期試驗(yàn)中，在減重與改善A1C方面均優(yōu)于司美格魯肽。CagriSema由長(zhǎng)效胰淀素類(lèi)似物cagrilintide（2.4 mg）與司美格魯肽（2.4 mg）組成。此外，Zealand Pharma與艾伯維（AbbVie）旗下的胰淀素靶向療法petrelintide與ABBV-295也在本季度分別公布了用于治療肥胖患者的2期與1期試驗(yàn)積極結(jié)果。

值得注意的是，GLP-1療法的應(yīng)用范圍正在逐步拓展至代謝疾病之外。禮來(lái)在本季度宣布，其GLP-1/GIP雙重受體激動(dòng)劑Zepbound（tirzepatide）聯(lián)合IL-17A單抗Taltz（ixekizumab），在兩項(xiàng)分別針對(duì)中重度斑塊狀銀屑病及活動(dòng)性銀屑病關(guān)節(jié)炎（PsA）肥胖或超重患者的3期試驗(yàn)中均達(dá)到主要終點(diǎn)。這些結(jié)果顯示，GLP-1類(lèi)療法有望與銀屑病生物制品形成新的聯(lián)合治療策略。

除GLP-1相關(guān)療法外，本季度多項(xiàng)多肽療法也在其他疾病領(lǐng)域取得進(jìn)展。例如，Priavoid旗下靶向β-淀粉樣蛋白（Aβ）寡聚體的口服多肽療法PRI-002在2期試驗(yàn)中顯示，其淀粉樣相關(guān)影像學(xué)異常（ARIA）發(fā)生率與既往3期研究中安慰劑組水平相當(dāng)。此外，一項(xiàng)1/2期試驗(yàn)結(jié)果顯示，一名同時(shí)患有家族性腺瘤性息肉病（FAP）及相關(guān)硬纖維瘤的患者在接受Parabilis Medicines潛在“first-in-class”多肽療法zolucatetide治療60周后，十二指腸息肉病變顯著改善。與治療前評(píng)估相比，該患者息肉數(shù)量和大小均明顯減少，疾病分期由Spigelman II期降至I期，同時(shí)硬纖維瘤直徑減少了52.2%。根據(jù)新聞稿，zolucatetide是首個(gè)直接抑制β-catenin與TCF相互作用的抑制劑。

研發(fā)合作與融資進(jìn)展

在產(chǎn)業(yè)合作方面，本季度多家大型藥企圍繞多肽療法達(dá)成金額達(dá)數(shù)億美元甚至數(shù)十億美元的合作協(xié)議。今年1月，阿斯利康（AstraZeneca）與石藥集團(tuán)達(dá)成最高可達(dá)35億美元的戰(zhàn)略合作，雙方將共同推進(jìn)覆蓋肥胖癥與2型糖尿病的8項(xiàng)下一代療法研發(fā)。根據(jù)協(xié)議，雙方將首先推進(jìn)其中4個(gè)項(xiàng)目，這些項(xiàng)目將結(jié)合石藥集團(tuán)AI驅(qū)動(dòng)的肽類(lèi)藥物發(fā)現(xiàn)平臺(tái)以及其專(zhuān)有的LiquidGel每月一次給藥平臺(tái)技術(shù)。此外，諾華（Novartis）在2月與Unnatural Products（UNP）達(dá)成總金額超過(guò)17億美元的大環(huán)肽合作，進(jìn)一步加碼這一新興分子領(lǐng)域。

融資方面，多家創(chuàng)新公司也獲得資本市場(chǎng)支持。Parabilis Medicines在今年初完成超過(guò)3億美元的F輪融資，所獲資金將用于推進(jìn)zolucatetide的開(kāi)發(fā)。同時(shí)，峰肽藥業(yè)（Pinnacle Medicines）也于3月時(shí)完成8900萬(wàn)美元的B輪融資，用于加速管線(xiàn)的臨床推進(jìn)。

▲2026年第一季度多肽藥物領(lǐng)域部分投融資信息

一體化平臺(tái)助力多肽藥物創(chuàng)新

隨著多肽療法在肥胖、代謝疾病以及更多創(chuàng)新適應(yīng)癥中的研發(fā)不斷推進(jìn)，其分子設(shè)計(jì)也正變得愈發(fā)復(fù)雜。從脂肪酸修飾、PEG化，到蛋白融合與多肽偶聯(lián)等策略，越來(lái)越多的新一代多肽分子通過(guò)結(jié)構(gòu)改造實(shí)現(xiàn)更長(zhǎng)半衰期或更優(yōu)藥效。然而，這些創(chuàng)新設(shè)計(jì)在帶來(lái)治療潛力提升的同時(shí)，也對(duì)藥物開(kāi)發(fā)過(guò)程中的生物分析提出了更高要求。特別是在臨床研究階段，如何準(zhǔn)確解析多肽藥物的體內(nèi)暴露特征、免疫原性風(fēng)險(xiǎn)以及結(jié)構(gòu)修飾帶來(lái)的影響，已成為推動(dòng)相關(guān)療法順利進(jìn)入后期開(kāi)發(fā)的重要基礎(chǔ)。

在這一趨勢(shì)下，能夠同時(shí)支持藥代動(dòng)力學(xué)（PK）與免疫原性評(píng)價(jià)的系統(tǒng)化生物分析能力，正成為創(chuàng)新多肽藥物研發(fā)的重要技術(shù)支撐。為幫助合作伙伴更好地應(yīng)對(duì)這些挑戰(zhàn)，藥明康德生物分析部（BAS）依托高度成熟的生物分析技術(shù)平臺(tái)，構(gòu)建了面向新一代多肽藥物開(kāi)發(fā)需求的系統(tǒng)化分析解決方案，能夠有效應(yīng)對(duì)多肽分子在臨床試驗(yàn)中藥代動(dòng)力學(xué)與免疫原性研究的復(fù)雜挑戰(zhàn)。

隨著多肽藥物分子量增加、結(jié)構(gòu)修飾增多及偶聯(lián)形式日益復(fù)雜，其生物分析面臨一系列特有挑戰(zhàn)。例如，一方面，多肽在液相色譜串聯(lián)質(zhì)譜（LC-MS/MS）分析中通常呈現(xiàn)多電荷態(tài)分布及電離效率不均一，導(dǎo)致信號(hào)分散與離子抑制，從而影響檢測(cè)靈敏度與方法穩(wěn)健性；另一方面，多肽分子表位有限且與內(nèi)源性肽序列高度同源，往往表現(xiàn)為免疫原性較低、特異性抗體制備困難，同時(shí)在配體結(jié)合分析（LBA）中易出現(xiàn)內(nèi)源性干擾與交叉反應(yīng)，增加免疫原性評(píng)價(jià)的復(fù)雜性。此外，脂肪酸修飾、PEG化或蛋白融合等結(jié)構(gòu)改造在延長(zhǎng)半衰期的同時(shí)，也可能引入新的免疫原性風(fēng)險(xiǎn)（如抗PEG抗體），對(duì)抗藥抗體（ADA）與中和抗體（NAb）檢測(cè)提出更高要求。

針對(duì)上述行業(yè)痛點(diǎn)，藥明康德生物分析部整合高靈敏度LC-MS/MS、免疫捕獲-質(zhì)譜、ELISA/MSD平臺(tái)及細(xì)胞功能分析方法，實(shí)現(xiàn)PK分析、抗藥抗體（ADA）與中和抗體（NAb）評(píng)價(jià)的一體化支持。通過(guò)優(yōu)化樣本前處理策略、建立免疫捕獲-質(zhì)譜聯(lián)用技術(shù)及基于胰蛋白酶消化的bottom-up分析方法，可顯著提升檢測(cè)靈敏度并降低基質(zhì)干擾，在復(fù)雜修飾多肽及長(zhǎng)鏈多肽分析中表現(xiàn)出良好的方法特異性與穩(wěn)健性。同時(shí)，針對(duì)多肽藥物免疫原性評(píng)價(jià)中的低免疫原性與高同源性帶來(lái)的檢測(cè)難點(diǎn)，團(tuán)隊(duì)建立了分層（tiered）免疫原性評(píng)價(jià)體系，整合橋式（bridging）ADA檢測(cè)、確認(rèn)實(shí)驗(yàn)及滴度分析，并結(jié)合酸解離（ACE）、MRD優(yōu)化等策略提升藥物耐受性與檢測(cè)靈敏度；通過(guò)優(yōu)化標(biāo)記試劑設(shè)計(jì)及方法學(xué)條件，有效降低內(nèi)源性干擾與非特異性結(jié)合，并結(jié)合細(xì)胞功能性NAb分析方法，實(shí)現(xiàn)從ADA篩查到中和效應(yīng)評(píng)價(jià)的全流程覆蓋，從而系統(tǒng)性支持復(fù)雜修飾多肽及偶聯(lián)多肽藥物的免疫原性風(fēng)險(xiǎn)評(píng)估。

藥明康德生物分析技術(shù)平臺(tái)已成功支持GLP-1類(lèi)似物、胰島素類(lèi)似物等新一代多肽藥物的臨床PK研究及免疫原性評(píng)估，形成覆蓋方法開(kāi)發(fā)、驗(yàn)證到樣本檢測(cè)的端到端能力。依托標(biāo)準(zhǔn)化流程與多技術(shù)協(xié)同優(yōu)勢(shì)，藥明康德生物分析部能夠?yàn)楹献骰锇樘峁└哽`敏度、高可靠性的多肽藥物生物分析支持，加速創(chuàng)新多肽療法從研究階段邁向臨床開(kāi)發(fā)。

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 semaglutideWegovy 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 tabletRybelsusin 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 therapyIcotyde (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 drugImcivree (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) approvedAspaveli (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 agonistretatrutide, 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 agonistPF-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 agonistVK2735reported Phase 2 results published in Obesity, while enrollment for its Phase 3 trial was completed this quarter. Altimmune’s candidatepemvidutidereceived 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 therapyCagriSemaoutperformed 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 therapiespetrelintideandABBV-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 agonistZepbound (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 withzolucatetide, 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.

參考資料：

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