Ustekinumab biosimilar (Alvotech)

来源：药渡 撰文：幻目     编辑：维他命 截至目前为止，FDA在2024年已经批准了一些重磅新药，包括礼来公司治疗阿尔茨海默病的Kisunla和Madrigal制药公司治疗代谢功能障碍相关脂肪性肝炎的Rezdiffra，BMS的35年来第一种新型精神分裂症药物KarXT等…… 相关内容回顾： 盘点：11月FDA批准上市的重磅药物 新药速递：FDA10月批准药物盘点 12月又有一些新药获批，以下汇总了12月FDA批准药物的相关信息。 01 Zepbound 研发企业：礼来 适应症：成人肥胖症的中度至重度阻塞性睡眠呼吸暂停 礼来的Zepbound（tirzepatide）已经是减肥领域的一枚重磅炸弹。近日，FDA宣布，现在Zepbound可用于治疗肥胖成人的中度至重度阻塞性睡眠呼吸暂停，并指出该药物需与饮食和运动相结合。 FDA的批准基于两项随机、双盲、安慰剂对照研究——一组为使用气道正压通气（PAP）治疗的患者，另一组未进行PAP治疗患者，469名受试者者均不患有2型糖尿病。在每周一次使用Zepbound（10或15毫克）或安慰剂52周后，服用Lilly药物的受试者的呼吸暂停或低通气事件减少，具有统计学意义和临床意义。除此外还伴随着体重减轻，FDA表示这可能有助于改善呼吸暂停症状。 02 Alyftrek 研发企业：Vertex Pharmaceuticals 适应症：患有囊性纤维化且至少有一个F508del突变或另一个CFTR基因突变且对治疗有反应的成人和6岁及以上儿童 Vertex Pharmaceuticals表示，FDA已批准其囊性纤维化新产品Alyftrek，这是对Trikafta的改良。Trikafta在2023年的销售额为89亿美元。 Alyftrek是一种Vanzacaftor/Tezacaftor/Deutivacaftor三联疗法，Vanzacaftor和Tezacaftor旨在通过促进CFTR蛋白的加工和运输，增加细胞表面CFTR蛋白数量，而Deutivacaftor旨在增加送达细胞表面的CFTR蛋白的通道开放概率，以改善细胞膜上盐和水的流动。FDA此次批准三联疗法上市主要是基于3项III期研究的积极结果。 03 Alhemo 研发企业：诺和诺德 适应症：患有血友病A或B的成人和12岁以上儿童 Alhemo是一种组织因子途径抑制剂（TFPI）拮抗剂，适用于皮下注射。近日，诺和诺德的Alhemo获得批准，用于预防成人和12岁及以上血友病A或B儿童的出血发作或降低出血频率。这些患者体内存在凝血因子抑制物。 该批准得到了一项关键试验的支持，在试验中，与对照组相比，Alhemo将自发性和创伤性出血的频率降低了86%。 Alhemo将与辉瑞每周一次的皮下血友病治疗药物Hympavzi竞争，后者于10月获得FDA批准（详情可见：重磅首款！每周一次，辉瑞长效血友病疗法获FDA批准）。据EndpointsNews报道，Hympavzi仅被批准用于体内没有凝血因子抑制物的血友病A和B患者，但辉瑞预计明年将获得Hympavzi在有抑制物患者中的数据，可能支持标签扩展。 04 Ensacove 研发企业：Xcovery 适应症：ALK阳性局部晚期或转移性非小细胞肺癌 Xcovery Holdings的Ensacove（ensartinib）获得了FDA的批准，用于治疗ALK阳性局部晚期或转移性小细胞肺癌（NSCLC）患者。Ensacove已获准用于一线治疗。 ALK是一个主要参与发育的基因，在健康的情况下，它在出生前就被关闭了。然而，在某些情况下，该基因被重新激活并与邻近基因融合——这种突变可导致不同类型的癌症，例如淋巴瘤和NSCLC。 Ensacove是一种口服酪氨酸激酶抑制剂，通过破坏ALK介导的信号传导来解决ALK阳性NSCLC，进而阻断癌细胞典型的过度活跃的生长和增殖。 Ensacove III期eXalt3试验表明，Ensacove显著改善了辉瑞的Xalkori（克唑替尼）的无进展生存期。 05 Steqeyma 研发企业：Celltrion 适应症：成人和儿童斑块状银屑病和银屑病关节炎、成人克罗恩病和溃疡性结肠炎 在FDA批准了Celltrion的生物仿制药Steqeyma之后，强生公司重磅免疫疗法Stelara（优特克单抗）将面临更激烈的竞争。Steqeyma计划于2025年2月在美国上架，将以皮下注射和静脉输注的形式给药。 Steqeyma的批准基于斑块状银屑病的III期研究结果，该研究表明，该生物仿制药在疗效或安全性方面与Stelara没有临床意义的差异。 Steqeyma是Stelara生物仿制药列表中的最新成员。4月，FDA还批准了Teva和Alvotech的Selarsdi，该药可用于斑块状银屑病和银屑病关节炎，但不能用于克罗恩病和溃疡性结肠炎。Selarsdi将于2025年初推出。7月，监管机构批准了Samsung Bioepis的Pyzchiva，该公司也获得了互换性的临时许可。Pyzchiva将于2025年2月22日由Sandoz在美国进行商业化。 06 Nemluvio 研发企业：Galderma 适应症：中度至重度特应性皮炎 FDA批准了皮下注射剂Nemluvio（nemolizumab-ilto），用于12岁及以上患有中度至重度特应性皮炎的患者。建议将Nemluvio与局部皮质类固醇和/或钙调磷酸酶抑制剂一起给药。 Nemluvio是一种人源化IgG2单克隆抗体，靶向IL-31受体并破坏其下游信号传导，进而抑制炎症、纤维化和表皮失调。它的批准得到了III期ARCADIA临床试验计划的支持，该计划包括1,700多名患者，与安慰剂相比，每4周给药一次的Nemluvio可显著改善皮肤清除率。此外，Nemluvio还显著缓解了瘙痒且减少了睡眠障碍。 Galderma的目标是Nemluvio的峰值销售额超过20亿美元，预计到2027年底Nemluvio将达到重磅炸弹的地位。 07 Vtama 研发企业：Organon 适应症：特应性皮炎 FDA批准外用乳膏Vtama（taparinof）用于治疗特应性皮炎。Vtama可用于成人患者和年仅2岁的儿童。 Vtama是一种芳烃受体激动剂，Vtama于2022年5月首次被批准用于治疗斑块状银屑病。 关键临床试验ADORING的结果支持Vtama的应用，该试验确定了Vtama在帮助患者获得清晰或几乎清晰的皮肤方面优于安慰剂。此外，一项长期扩展研究确定Vtama的效果是持久的，并且在48周的随访中其耐受性仍然良好。 08 Crenessity 研发企业：Neurocrine 适应症：先天性肾上腺皮质增生症 Neurocrine的Crenessity（crinecerfont）获得批准，成为该领域七十年来第一种新的先天性肾上腺皮质增生症（CAH）药物。 CAH是一种罕见的遗传病，其特征是缺乏重要的肾上腺类固醇激素，包括皮质醇、醛固酮和肾上腺雄激素。CAH患者会出现脱水和呕吐，严重时会导致盐分流失甚至死亡。在Crenessity获得批准之前，患者使用糖皮质激素控制症状，糖皮质激素可以帮助纠正酶失衡，但可能会带来骨质疏松症和糖尿病等副作用。 Crenessity通过选择性阻断CRF1受体来帮助调节ACTH和其他肾上腺雄激素。其批准得到了III期CAHtalyst研究数据的支持，该研究表明Crenessity显著降低了成人和儿童患者的雄烯二酮浓度，使他们能够在不影响治疗效果的情况下逐渐减少糖皮质激素剂量。 然而，该产品还存在一些风险，包括“急性肾上腺皮质功能不全或肾上腺危象伴糖皮质激素治疗不足的风险”的黑框警告。该公司表示，预计要到2025年下半年才能实现广泛的商业准入。 09 Unloxcyt 研发企业：Checkpoint Therapeutics 适应症：转移性或局部晚期皮肤鳞状细胞癌 FDA批准使用Checkpoint Therapeutics的PD-L1抑制剂Unloxcyt治疗转移性或局部晚期皮肤鳞状细胞癌患者。 Unloxcyt是第一个也是唯一一个适用于该适应症的PD-L1阻断剂，Unloxcyt是一种人类免疫球蛋白G1（IgG1）单克隆抗体，具有双重作用机制，其一，结合PD-L1并阻断PD-L1与其受体PD-1和B7.1之间的相互作用。这种相互作用产生对抗肿瘤免疫反应的抑制作用。其二，可在体外诱导抗体依赖性细胞介导的细胞毒性。 Unloxcyt的批准得到了关键数据的支持，该数据显示，转移性和局部晚期疾病患者的确认客观缓解率分别为47.4%和54.8%。 10 Imfinzi 研发企业：阿斯利康 适应症：局限期小细胞肺癌 阿斯利康宣布，美国FDA批准Imfinzi（durvalumab，度伐利尤单抗）的新适应症上市申请，用于治疗在同时进行铂类化疗和放疗（cCRT）后病情未进展的局限期小细胞肺癌（LS-SCLC）成年患者。 IMFINZI是目前唯一获批用于局限期和广泛期小细胞肺癌的免疫疗法，该批准得到了III期ADRIATIC研究数据的支持，根据2024年4月的读数，该研究达到了总生存期和的主要疗效终点。与安慰剂相比，Imfinzi治疗可将死亡风险降低27%，同时将无进展生存期延长24%。两种效应均具有统计学意义。 11 Bizengri 研发企业：Merus 适应症：具有NGR1突变的胰腺癌和非小细胞肺癌 Merus的双特异性抗体Bizengri（zenocutuzumab）成为晚期不可切除或转移性胰腺癌和具有NRG1基因融合的非小细胞肺癌的第一个也是唯一一个疗法。FDA在其加速途径下批准了zenocutuzumab，但Merus需要在验证性试验中验证Bizengri的临床益处，以使其继续投放市场。 Bizengri是一种双特异性抗体，能结合表达在细胞（包括肿瘤细胞）表面的HER2和HER3的细胞外结构域，抑制HER2与HER3形成二聚体并阻止NRG1与HER3的结合。它通过减少细胞增殖及PI3K-AKT-mTOR信号通路传导发挥作用。此外，Bizengri能介导抗体依赖的细胞毒性（ADCC）。 FDA的加速批准得到了eNRGy研究的支持，该研究称胰腺癌和非小细胞肺癌患者的总体缓解率分别为40%和33%。前者患者组的反应持续时间长达16.6个月，而后一组的中位持续时间为7.4个月。 12 Yesintek 研发企业：Biocon Biologics 适应症：克罗恩病、溃疡性结肠炎、斑块状银屑病和银屑病关节炎 FDA批准了Biocon Biologics的Yesintek（ustekinumab-kfce），这是一种与强生公司的重磅抗体药物Stelara类似的生物仿制药。 与其参比制剂一样，Yesintek适用于斑块状银屑病和银屑病关节炎，以及炎症性肠病克罗恩病和溃疡性结肠炎。根据2024年2月与J&J的和解协议，Biocon将能够在2025年2月22日之前在美国推出Yesintek。 随着Yesintek的批准，Stelara仿制药越来越多，包括Teva和Alvotech的Selarsdi（于2024年4月获得批准），以及三星Bioepics的Pyzchiva。 参考资料： https://www.biospace.com/biospace-fda-decision-tracker *声明：本文仅是介绍医药疾病领域研究进展或简述研究概况或分享医药相关讯息，并非也不会进行治疗或诊断方案推荐，也不对相关投资构成任何建议。内容如有疏漏，欢迎沟通指出！ 7亿美元！济民可信抗IgE单抗成功出海，授权于RAPT 盘点：2024年值得关注的5项失败的临床试验 治疗脱发！浙大团队开发出新型局部给药的PROTAC降解剂

Addition is part of the annual reconstitution of the Nasdaq Biotech Index (NBI)Inclusion criteria include minimum market capitalization and daily trading volumes REYKJAVIK, Iceland, Dec. 23, 2024 (GLOBE NEWSWIRE) -- Alvotech (NASDAQ: ALVO), a global biotech company specializing in the development and manufacture of biosimilar medicines for patients worldwide, today announced that its stock will be added to the Nasdaq Biotechnology Index (NASDAQ: NBI). The addition comes as a part of the annual reconstitution of the index. Alvotech’s inclusion in the NBI will be effective when the U.S. market opens on Monday, December 23, 2024. The Nasdaq Biotechnology Index contains securities of Nasdaq-listed companies classified according to the Industry Classification Benchmark as either Biotechnology or Pharmaceuticals. The Nasdaq Biotechnology Index is calculated under a modified capitalization-weighted methodology. Companies in the Nasdaq Biotechnology Index must meet various eligibility requirements, including minimum market capitalization and average daily trading volume, among other criteria. Nasdaq selects new constituents of the NBI once annually, in December. About AlvotechAlvotech is a biotech 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. Two biosimilars, to Humira® (adalimumab) and Stelara® (ustekinumab) are already approved and marketed in multiple global markets. The current development pipeline includes nine disclosed biosimilar candidates aimed at treating autoimmune disorders, eye disorders, osteoporosis, respiratory disease, 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. Alvotech’s commercial partners include Teva Pharmaceuticals, a US affiliate of Teva Pharmaceutical Industries Ltd. (US), STADA Arzneimittel AG (EU), Fuji Pharma Co., Ltd (Japan), Advanz Pharma (EEA, UK, Switzerland, Canada, Australia and New Zealand), Dr. Reddy’s (EEA, UK and US), Biogaran (FR), Cipla/Cipla Gulf/Cipla Med Pro (Australia, New Zealand, South Africa/Africa), JAMP Pharma Corporation (Canada), Yangtze River Pharmaceutical (Group) Co., Ltd. (China), DKSH (Taiwan, Hong Kong, Cambodia, Malaysia, Singapore, Indonesia, India, Bangladesh and Pakistan), YAS Holding LLC (Middle East and North Africa), Abdi Ibrahim (Turkey), Kamada Ltd. (Israel), Mega Labs, Stein, Libbs, Tuteur and Saval (Latin America) and Lotus Pharmaceuticals Co., Ltd. (Thailand, Vietnam, Philippines, and South Korea). Each commercial partnership covers a unique set of product(s) and territories. Except as specifically set forth therein, Alvotech disclaims responsibility for the content of periodic filings, disclosures and other reports made available by its partners. 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 investor portal, and our website or follow us on social media on LinkedIn, Facebook, Instagram, X and YouTube. Alvotech Forward Looking StatementsCertain 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 generally relate to future events or the future financial operating performance of Alvotech and may include, for example, Alvotech’s expectations regarding competitive advantages, business prospects and opportunities including pipeline product development, future plans and intentions, results, level of activities, performance, goals or achievements or other future events, regulatory submissions, review and interactions, the potential approval and commercial launch of its product candidates, the timing of regulatory approval, and market launches. In some cases, you can identify forward-looking statements by terminology such as “may”, “should”, “expect”, “intend”, “will”, “estimate”, “anticipate”, “believe”, “predict”, “potential”, “aim” or “continue”, or the negatives of these terms or variations of them or similar terminology. 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: (1) the ability to maintain criteria for inclusion in stock market indexes; (2) the ability to maintain stock exchange listing standards; (3) changes in applicable laws or regulations; (4) the possibility that Alvotech may be adversely affected by other economic, business, and/or competitive factors; (5) Alvotech’s estimates of expenses and profitability; (6) Alvotech’s ability to develop, manufacture and commercialize the products and product candidates in its pipeline; (7) actions of regulatory authorities, which may affect the initiation, timing and progress of clinical studies or future regulatory approvals or marketing authorizations; (8) the ability of Alvotech or its partners to respond to inspection findings and resolve deficiencies to the satisfaction of the regulators; (9) the ability of Alvotech or its partners to enroll and retain patients in clinical studies; (10) the ability of Alvotech or its partners to gain approval from regulators for planned clinical studies, study plans or sites; (11) the ability of Alvotech’s partners to conduct, supervise and monitor existing and potential future clinical studies, which may impact development timelines and plans; (12) Alvotech’s ability to obtain and maintain regulatory approval or authorizations of its products, including the timing or likelihood of expansion into additional markets or geographies; (13) the success of Alvotech’s current and future collaborations, joint ventures, partnerships or licensing arrangements; (14) Alvotech’s ability, and that of its commercial partners, to execute their commercialization strategy for approved products; (15) Alvotech’s ability to manufacture sufficient commercial supply of its approved products; (16) the outcome of ongoing and future litigation regarding Alvotech’s products and product candidates; (17) the impact of worsening macroeconomic conditions, including rising inflation and interest rates and general market conditions, conflicts in Ukraine, the Middle East and other global geopolitical tension, on the Company’s business, financial position, strategy and anticipated milestones; and (18) other risks and uncertainties 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. Nothing in this communication should be regarded as a representation by any person that the forward-looking statements set forth herein will be achieved or that any of the contemplated results of such forward-looking statements will be achieved. You should not place undue reliance on forward-looking statements, which speak only as of the date they are made. 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. The recipient agrees that it shall not seek to sue or otherwise hold Alvotech or any of its directors, officers, employees, affiliates, agents, advisors, or representatives liable in any respect for the provision of this communication, the information contained in this communication, or the omission of any information from this communication. ALVOTECH INVESTOR RELATIONS AND GLOBAL COMMUNICATIONSBenedikt Stefansson, VPalvotech.ir@alvotech.com