Ustekinumab

REYKJAVIK, ICELAND (August 21, 2026) — Alvotech (NASDAQ: ALVO; ALVO-SDB), a global biotechnology company specializing in the development and manufacture of biosimilar medicines for patients worldwide, today announced a strategic licensing and commercialization agreement with Lotus Pharmaceutical (TWSE Stock Code: 1795) covering two of Alvotech’s candidates in the United States and selected Asian markets: AVT34, a proposed biosimilar to Imfinzi® (durvalumab), and AVT87, a proposed biosimilar to Hemlibra® (emicizumab). Imfinzi® is an oncology biologic used in the treatment of multiple cancers, which generated global sales of approximately $6.1 billion in 2025¹. Hemlibra® is a biologic for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A that generated global sales of approximately CHF4.8 billion (approximately $5.8 billion) in 2025². Under a semi-exclusive agreement in the United States, Alvotech retains the right to commercialize both products directly alongside Lotus, while Lotus will commercialize the products through Alvogen, its U.S.-based wholly owned subsidiary. Alvotech will retain responsibility for product development, and for obtaining and maintaining marketing authorizations in the United States, and will serve as the exclusive supplier of the products for all markets. In Asia, Lotus will have exclusive commercialization rights in eight selected markets: South Korea, Taiwan, Thailand, Vietnam, the Philippines, Singapore, Hong Kong and Malaysia. Lotus will be responsible for local regulatory submissions and commercialization in these markets. The agreement has a potential value to Alvotech of up to approximately $150 million in upfront and milestone payments, in addition to ongoing revenues from the supply of commercial product. “This agreement represents an important evolution of Alvotech’s commercial strategy,” said Lisa Graver, Chief Executive Officer of Alvotech. “For the first time, we will have the opportunity to participate directly in the future commercialization of our products in the United States, allowing us to retain a greater share of the value we create through our development and manufacturing platform. At the same time, our partnership with Lotus extends the potential reach of these two important pipeline assets across key Asian markets. We look forward to working together to bring these medicines to patients and broaden access to high-quality biologics.” “We are pleased to partner with Alvotech on two important biosimilar candidates that meaningfully advance Lotus’ global growth strategy,” said Petar Vazharov, Chief Executive Officer of Lotus. “By combining Alvotech’s integrated biosimilar development and manufacturing capabilities with Alvogen’s established U.S. commercial platform and Lotus’s deep market presence across Asia, we are building a strong foundation for the future commercialization of AVT34 and AVT87 across key global markets. These candidates expand the scale and reach of our biosimilar portfolio in oncology and rare diseases, and reinforces our commitment to broadening access to high-quality medicines.” Imfinzi® and Hemlibra® are registered trademarks and the property of their respective owners. 1) AstraZeneca PLC. (2026). Annual report on Form 20-F for the fiscal year ended December 31, 2025. U.S. Securities and Exchange Commission. https://www.sec.gov/Archives/edgar/data/901832/000110465926019130/azn-20251231x20f.htm2) Roche, Finance Report 2025, F. Hoffmann-La Roche Ltd, https://assets.roche.com/f/176343/x/fca190f63e/fb25e.pdf Contacts Media contacts – alvotech.media@alvotech.comBenedikt StefanssonSarah MacLeod Investor Relations contacts – alvotech.ir@alvotech.comDr. Balaji V PrasadBenedikt Stefansson About Alvotech Alvotech is a biotechnology company, founded by Robert Wessman, focused solely on the development and manufacture of biosimilar medicines for patients worldwide. Alvotech seeks to be a global leader in the biosimilar space by delivering high-quality, cost-effective products and services, enabled by a fully integrated approach and broad in-house capabilities. Five biosimilars are already approved and marketed in multiple global markets, including biosimilars to Humira® (adalimumab), Stelara® (ustekinumab), Simponi® (golimumab), Eylea® (aflibercept) and Prolia®/Xgeva® (denosumab). The current development pipeline includes disclosed biosimilar candidates aimed at treating autoimmune disorders, eye disorders, and cancer. Alvotech has formed a network of strategic commercial partnerships to provide global reach and leverage local expertise in markets that include the United States, Europe, Japan, China, and other Asian countries and large parts of South America, Africa and the Middle East. For more information, please visit https://www.alvotech.com. None of the information on the Alvotech website shall be deemed part of this press release. For more information, please visit our website or follow us on social media on LinkedIn, Facebook, Instagram, and YouTube. Forward Looking Statements Certain statements in this communication may be considered “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements include, for example, Alvotech’s expectations regarding competitive advantages, business prospects and opportunities including pipeline product development, future plans and intentions, regulatory submissions, review and interactions, the potential approval and commercial launch of its product candidates, the timing of regulatory approval, market launches and financial projections. Such forward-looking statements are subject to risks, uncertainties, and other factors which could cause actual results to differ materially from those expressed or implied by such forward-looking statements. These forward-looking statements are based upon estimates and assumptions that, while considered reasonable by Alvotech and its management, are inherently uncertain and are inherently subject to risks, variability, and contingencies, many of which are beyond Alvotech’s control. Factors that may cause actual results to differ materially from current expectations include, but are not limited to factors set forth in the sections entitled “Risk Factors” and “Cautionary Note Regarding Forward-Looking Statements” in documents that Alvotech may from time-to-time file or furnish with the SEC. There may be additional risks that Alvotech does not presently know or that Alvotech currently believes are immaterial that could also cause actual results to differ from those contained in the forward-looking statements. These forward-looking statements are provided for illustrative purposes only and are not intended to serve as, and must not be relied on by an investor as, a guarantee, assurance, prediction or definitive statement of a fact or probability. Alvotech does not undertake any duty to update these forward-looking statements or to inform the recipient of any matters of which any of them becomes aware of which may affect any matter referred to in this communication. Alvotech disclaims any and all liability for any loss or damage (whether foreseeable or not) suffered or incurred by any person or entity as a result of anything contained or omitted from this communication and such liability is expressly disclaimed.

“本材料仅供中国大陆境内的医疗卫生专业人员作为学术参考，而非针对一般公众，亦非广告用途。医疗卫生专业人员在做出任何与治疗有关的决定时，应根据患者的具体情况，参照药监局核准的药品说明书。如果您不是卫生医疗专业人士，请勿阅读和/或传播本材料。” 克罗恩病（Crohn’s Disease，CD）是一种慢性、透壁性、炎症性肠病，好发于青壮年，常伴狭窄、瘘管等严重并发症1。近年来，生物制剂的应用极大改善了CD患者的预后，但临床诊疗仍面临早期诊断困难、鉴别诊断复杂及疗效“天花板”等挑战。2025年，全球首个靶向IL-23 p19亚基的CD治疗药物利生奇珠单抗在中国获批上市，并于2026年1月纳入国家医保目录，为众多CD患者提供了新的治疗选择。武汉大学中南医院炎症性肠病中心叶梅团队在利生奇珠单抗的临床应用中积累了丰富经验，现通过三例典型病例，与全国同道交流分享。 病例一：阑尾子镜破困局——严重狭窄下的精准诊断 病史概要： 患者男性，37岁，因腹痛、腹泻6个月就诊。大便2-3次/日，伴间断右下腹隐痛，体重未见明显变化。外院肠镜检查提示回盲部狭窄，临床疑诊CD；予全肠内营养联合美沙拉嗪治疗，效果不佳。 诊断难点： 本病例最具挑战之处在于患者回盲瓣严重狭窄，常规结肠镜及小肠镜均无法通过，既无法观察末端回肠及小肠病变，更重要的是无法获取小肠组织病理，诊断陷入僵局。回盲部狭窄是CD的常见并发症，当管腔狭窄严重到常规内镜无法通过时，临床医生常面临“无病理、难确诊”的困境。该患者尚未出现频繁肠梗阻，暂无手术意愿，如何在创伤最小的情况下获取病理证据成为亟待解决的核心问题。 突破性方案： 在与患者充分沟通后，团队决定尝试一项创新性操作——阑尾子镜检查。阑尾子镜直径为3 mm，远细于常规内镜，具备通过极度狭窄腔道的独特优势。在精细操控下，子镜顺利通过狭窄段，进入末端回肠，镜下清晰观察到多发纵行溃疡，部分呈纵行裂隙样改变——此为CD特征性内镜表现（图1）。团队随即在直视下完成精准活检，成功获取病理标本。 图1 借助阑尾子镜顺利通过狭窄段，进入末端回肠，清晰观察到纵行溃疡 最终诊断： 克罗恩病（A2L1+4bB2，中度活动期）。 治疗方案与转归： 明确诊断后，团队与患者充分沟通、评估，启动利生奇珠单抗治疗。治疗6个月后复查，患者达到临床缓解、生化指标缓解及影像学缓解，腹痛、腹泻症状基本消失，炎症指标恢复正常，影像学显示肠壁炎症明显改善。 病例启示： 内镜无法通过并非诊断的终点，阑尾子镜为管腔极度狭窄的患者开辟了一条微创病理获取的新路径，值得临床借鉴。 病例二：肠结核还是克罗恩病？——诊断性治疗后的精准抉择 病史概要： 患者男性，20岁，因右下腹痛1月余就诊，伴发热、纳差、乏力，大便稀糊。外院肠镜示：回盲部充血肿胀、呈结节样改变，回肠末端见可疑小瘘口，病理提示慢性活动性炎症。转入我院后，查炎症指标升高，T-SPOT试验结果强阳性；结肠镜见回盲部及结肠溃疡；小肠CT符合炎症性肠病影像学表现；回盲瓣活检病理见肉芽肿形成。 诊疗难点： 本病例的核心难点在于肠结核与CD的鉴别诊断。回盲部为肠结核和CD的共同好发部位，两者在临床表现、内镜征象乃至病理特征上均存在重叠。T-SPOT强阳性提示结核感染可能，但肉芽肿形成既可见于肠结核，也可见于CD。在临床表现不典型的情况下，贸然使用生物制剂可能激活潜伏结核，而延误CD治疗则可能导致疾病进展，鉴别诊断至关重要。 诊疗策略： 鉴于肠结核尚不能完全排除，团队采取“诊断性抗结核治疗”策略——先给予3个月规范抗结核治疗，同时密切观察临床及内镜变化。3个月后复查肠镜示结肠溃疡未愈合，遂行再次系统活检，病理结果最终支持CD诊断（图2）。 图2（A）初诊时回盲部及结肠可见多发溃疡；（B）规范抗结核治疗3个月后，回盲部及结肠多发溃疡未见好转；（C）利生奇珠单抗治疗6个月后黏膜愈合 最终诊断： 克罗恩病（A2L3B2，中度活动期）。 治疗方案与转归： 排除肠结核后，团队启动利生奇珠单抗治疗。治疗6个月后复查，患者达到临床缓解、生化指标缓解及内镜下缓解。 病例启示： 在结核高流行地区，肠结核与CD的鉴别是临床常态，而非例外。诊断性抗结核治疗是鉴别二者的经典策略，但必须设定明确的观察终点和时限。3个月是临床常用的观察窗口——若规范抗结核治疗后内镜下病变无明显改善，应高度怀疑CD并及时重新评估诊断。同时，这一病例也提醒我们，在启动生物制剂前，严格的结核筛查不可或缺2。 病例三：抗抗体阳性的“换药”——英夫利西单抗失效后的新选择 病史概要： 患者女性，22岁，确诊CD 3年余。曾因小肠穿孔行小肠部分切除+狭窄成形术，术后病理证实CD，术后给予规律英夫利西单抗治疗，2023年实现临床、生化和内镜下缓解。近2个月出现间断腹痛，伴炎症指标升高，影像学提示疾病复发；结肠镜示Rutgeerts评分i2（术后复发）。 诊疗难点： 本例核心问题在于生物制剂继发性失应答。患者既往英夫利西单抗治疗有效，但近期出现疾病复发——需明确系药物浓度不足抑或抗抗体产生，这决定了后续治疗策略的根本方向。 精准检测： 团队完善了英夫利西单抗药物浓度及抗抗体检测，结果显示抗抗体阳性——这意味着患者体内已产生针对英夫利西单抗的中和性抗体，继续使用该药不仅疗效有限，还可能诱发过敏反应。 方案调整： 鉴于抗抗体阳性，继续使用英夫利西单抗已无临床意义。团队与患者充分沟通后，决定转换治疗，调整为利生奇珠单抗。选择该药基于以下考量：其一，其靶向IL-23 p19亚基，作用机制与抗TNF-α药物完全不同，不存在交叉耐药；其二，相关研究中，对于既往生物制剂治疗失败的CD患者，IL-23 p19抑制剂展现了良好的疗效；其三，多项临床研究证实利生奇珠单抗在难治性CD患者中安全有效。 治疗和转归： 换用利生奇珠单抗治疗6个月后复查，患者达到临床缓解、生化指标缓解及内镜下缓解（图3）。 图3 （A）结肠镜检查提示末端回肠及回盲瓣多发溃疡；（B）利生奇珠单抗治疗6个月后黏膜愈合 病例启示： 生物制剂时代，“用不上”和“用不久”是两大临床困境。对于继发性失应答患者，精准检测（药物浓度和抗抗体）是决策的基础，而非盲目增加剂量或缩短给药间隔。一旦确认抗抗体阳性，及时转换为不同靶点的生物制剂是合理且有效的策略。利生奇珠单抗作为抗TNF-α失效后的后线选择，在本例中展现了令人满意的疗效。 利生奇珠单抗：精准靶向IL-23的新利器 利生奇珠单抗是人源化IgG1单抗，选择性结合IL-23 p19亚基，阻断致病性Th17通路，同时保留IL-12介导的抗感染免疫3,4。多项III期研究证实其诱导和维持缓解疗效优异5-7： ADVANCE研究和MOTIVATE研究5显示600 mg利生奇珠单抗诱导治疗12周，排便频率和腹痛评分（SF/AP）临床缓解率为43%和35%，内镜应答率为40%/29%； FORTIFY研究6中，利生奇珠单抗诱导治疗取得应答者继续使用利生奇珠单抗维持治疗至52周，360 mg组临床缓解率（SF/AP）为52%，内镜应答率为47%。 SEQUENCE研究7头对头比较研究显示，利生奇珠单抗在临床缓解、内镜缓解等多个终点上均显著优于乌司奴单抗。 并且在临床试验中，利生奇珠单抗耐受性良好，不良事件发生率与安慰剂相当。2026年纳入医保后，患者年治疗费用降至约1万多元，可及性大幅提升。 团队心得：精准诊断、精准决策、精准治疗 三例病例浓缩了CD管理的多重挑战。我们的体会是：诊断是治疗之基——面对肠道狭窄、鉴别困难等困境，应勇于创新，不轻易放弃病理证据；决策需精准导向——动态监测药物浓度和抗抗体，科学指导转换治疗时机；创新药物需规范应用——用药前严格筛查感染，个体化制定治疗方案。利生奇珠单抗为抗TNF-α原发性无应答或继发性失效、诊断困难、伴肠道狭窄和术后复发等复杂情况的CD患者提供了有效、安全的新选择。 CD虽尚不可治愈，但已可管可控。武汉大学中南医院消化内科叶梅团队始终致力于IBD精准诊疗，愿与全国同道携手，共同提升CD诊疗水平，让更多患者实现临床、内镜、生活质量的多重缓解目标。 专家简介 叶梅  教授 武汉大学中南医院 主任医师、博士生导师 美国约翰霍普金斯大学博士后 湖北省炎症性肠病专病医联体 理事长 中国炎症性肠病专病医联体理事会 理事 湖北省医学会消化病学分会 常委 中华医学会消化病学分会微生态学组 委员 中华医学会消化病学分会青少年消化协作组 委员 白求恩公益基金会消化专家委员会 委员 海峡两岸医药卫生交流协会消化病学分会 委员 国家自然科学基金通讯评审专家；教育部学位中心学位论文通讯评审专家；中国博士后科学基金评审专家 参考文献： 1. 中华医学会消化病学分会炎症性肠病学组, 中国炎症性肠病诊疗质量控制评估中心. 中国克罗恩病诊治指南（2023年·广州）. 中华炎性肠病杂志. 2024;8(1):2-32. 2. 中华医学会消化病学分会炎症性肠病学组, 中国炎症性肠病诊疗质量控制评估中心. 白细胞介素-23 p19 抑制剂治疗炎症性肠病患者临床规范化使用流程. 中华炎性肠病杂志. 2026;10(3):269-275. 3. Schmitt H, Neurath MF, Atreya R. Role of the IL23/IL17 Pathway in Crohn's Disease. Front Immunol. 2021;12:622934. 4. Singh S, Kroe-Barrett RR, Canada KA, et al. Selective targeting of the IL23 pathway: Generation and characterization of a novel high-affinity humanized anti-IL23A antibody. MAbs. 2015;7(4):778-791. 5. D’Haens G, Panaccione R, Baert F, et al. Risankizumab as induction therapy for Crohn’s disease: results from the phase 3 ADVANCE and MOTIVATE induction trials. Lancet 2022;399:2015–2030. 6. Ferrante M, Panaccione R, Baert F, et al. Risankizumab as maintenance therapy for moderately to severely active Crohn's disease: results from the multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial. Lancet. 2022;399(10340):2031-2046. 7. Peyrin-Biroulet L, Chapman JC, Colombel JF, et al. Risankizumab versus Ustekinumab for Moderate-to-Severe Crohn's Disease. N Engl J Med. 2024;391(3):213-223. 审批编码：CN-SKZG-260092，有效期至：7/31/2028，逾期视同作废。 欢迎投稿！ tougao@medvoices.cn 稿件类型：研究速递，综述译稿，指南/共识，病例分享。 版权属《消化医声》所有。欢迎个人转发分享。其他任何媒体、网站如需转载或引用本网版权所有之内容，须经本网授权同意（加小编微信：GI-2022）。