Pivekimab

Adds flagship antibody-drug conjugate (ADC) ELAHERE® (mirvetuximab soravtansine-gynx) for folate receptor-alpha (FRα) positive platinum-resistant ovarian cancer (PROC) to AbbVie's portfolio ImmunoGen's pipeline complements AbbVie's existing oncology pipeline with potential to be transformative across multiple solid tumors and hematologic malignancies ImmunoGen's late-stage development programs for ELAHERE provide opportunity to expand into earlier lines of therapy and additional patient populations AbbVie reaffirms previously issued 2024 full-year adjusted diluted EPS guidance range of $11.05-$11.25 which now includes a $0.42 per share dilutive impact related to the ImmunoGen acquisition and the pending Cerevel Therapeutics acquisition AbbVie updates previously issued 2024 first-quarter adjusted diluted EPS guidance range from $2.30-$2.34 to $2.26-$2.30 which now includes a $0.04 per share dilutive impact related to the ImmunoGen acquisition NORTH CHICAGO, Ill., Feb. 12, 2024 /PRNewswire/ -- AbbVie (NYSE: ABBV) announced today that it has completed its acquisition of ImmunoGen (NASDAQ: IMGN). With the completion of the acquisition, ImmunoGen is now part of AbbVie. "Together with ImmunoGen, we have the potential to continue redefining the standard of care for those living with cancer," said Robert A. Michael, president and chief operating officer, AbbVie. "The addition of ImmunoGen's treatment for ovarian cancer will accelerate our ability to help patients today, expand our oncology pipeline and drive long-term revenue growth well into the next decade. I want to thank ImmunoGen for their efforts to advance science for patients and we look forward to welcoming our new colleagues to AbbVie." ELAHERE® (mirvetuximab soravtansine-gynx) is the first and only antibody-drug conjugate (ADC) approved by the U.S. Food and Drug Administration (FDA) in ovarian cancer. The FDA granted accelerated approval for ELAHERE in folate receptor-alpha (FRα) positive platinum-resistant ovarian cancer (PROC) patients based on response data. Results from a confirmatory trial currently under review by the FDA show that ELAHERE is the first targeted agent to offer a survival benefit in PROC, with label expansion opportunities across larger segments of the ovarian cancer market. ImmunoGen's follow-on pipeline of ADCs further builds on AbbVie's existing solid tumor pipeline of novel targeted therapies and next-generation immuno-oncology assets, which have the potential to create new treatment possibilities across multiple solid tumors and hematologic malignancies. Through focused R&D efforts, AbbVie has developed novel ADC technology and has unique strengths in antibody engineering, drug linker chemistry and toxin research. AbbVie and ImmunoGen's combined capabilities represent an opportunity to deliver potentially transformative ADC therapies to patients. ImmunoGen's investigational Phase 1 asset, IMGN-151, is a next-generation FRα ADC for ovarian cancer with the potential for expansion into other solid tumor indications. Pivekimab sunirine, currently in Phase 2, is an investigational anti-CD123 ADC targeting blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare blood cancer, which was granted FDA breakthrough therapy designation for the treatment of relapsed/refractory BPDCN. For additional background on the acquisition, please read the announcement press release here and view AbbVie's investor presentation here. Financial Terms AbbVie has acquired all outstanding ImmunoGen common stock for $31.26 per share. It is expected that ImmunoGen's common stock will cease to trade on the NASDAQ stock exchange prior to market open on February 12, 2024. AbbVie expects its acquisition of ImmunoGen to be accretive to AbbVie's diluted EPS beginning in 2027 and significantly accretive over the long-term. Full-Year 2024 Outlook AbbVie is reaffirming its previously issued 2024 full-year adjusted diluted EPS guidance range of $11.05-$11.25. This guidance now includes a $0.42 per share dilutive impact related to the completed ImmunoGen acquisition, as well as the pending Cerevel Therapeutics acquisition, which is anticipated to close in mid-2024. AbbVie's 2024 adjusted diluted EPS guidance excludes any impact from acquired IPR&D and milestones that may be incurred during 2024, as both cannot be reliably forecasted. AbbVie is updating its previously issued 2024 first-quarter adjusted diluted EPS guidance range from $2.30-$2.34 to $2.26-$2.30. This guidance now includes a $0.04 per share dilutive impact related to the ImmunoGen acquisition. AbbVie's 2024 first-quarter adjusted diluted EPS guidance excludes any impact from acquired IPR&D and milestones that may be incurred in the quarter, as both cannot be reliably forecasted. About ELAHERE (mirvetuximab soravtansine-gynx) ELAHERE (mirvetuximab soravtansine-gynx) is a first-in-class ADC comprising a folate receptor alpha-binding antibody, cleavable linker, and the maytansinoid payload DM4, a potent tubulin inhibitor designed to kill the targeted cancer cells. ELAHERE is indicated for the treatment of adult patients with folate receptor-alpha (FRα) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. Select patients for therapy based on an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. The prescribing information includes a boxed warning. ELAHERE can cause severe ocular toxicities, including visual impairment, keratopathy, dry eye, photophobia, eye pain, and uveitis. Conduct an ophthalmic exam including visual acuity and slit lamp exam prior to initiation of ELAHERE, every other cycle for the first 8 cycles, and as clinically indicated. Administer prophylactic artificial tears and ophthalmic topical steroids. Withhold ELAHERE for ocular toxicities until improvement and resume at the same or reduced dose. Discontinue ELAHERE for Grade 4 ocular toxicities. Serious adverse reactions occurred in 31% of patients. The most common (≥2%) serious adverse reactions were intestinal obstruction (8%), ascites (4%), infection (3%), and pleural effusion (3%). Fatal adverse reactions occurred in 2% of patients, including small intestinal obstruction (1%) and pneumonitis (1%).The most common (≥20%) adverse reactions, including laboratory abnormalities, were vision impairment, fatigue, increased aspartate aminotransferase, nausea, increased alanine aminotransferase, keratopathy, abdominal pain, decreased lymphocytes, peripheral neuropathy, diarrhea, decreased albumin, constipation, increased alkaline phosphatase, dry eye, decreased magnesium, decreased leukocytes, decreased neutrophils, and decreased hemoglobin. Please see full Prescribing Information, including Boxed Warning for ELAHERE. About AbbVie in Oncology At AbbVie, we are committed to transforming standards of care for multiple blood cancers while advancing a dynamic pipeline of investigational therapies across a range of cancer types. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potential breakthrough medicines. We are evaluating more than 20 investigational medicines in over 300 clinical trials across some of the world's most widespread and debilitating cancers. As we work to have a remarkable impact on people's lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines. For more information, please visit . About AbbVie AbbVie's mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas – immunology, oncology, neuroscience, and eye care – and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at . Follow @abbvie on LinkedIn, Facebook, Instagram, X (formerly Twitter), and YouTube. Forward-Looking Statements Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions and uses of future or conditional verbs, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those expressed or implied in the forward-looking statements. Such risks and uncertainties include, but are not limited to, risks related to the ability to realize the anticipated benefits of the ImmunoGen acquisition on the anticipated timeframe or at all, risks that the cost to consummate the ImmunoGen acquisition or to obtain the anticipated benefits of the acquisition could be greater than expected, the risk that the ImmunoGen business will not be integrated successfully, disruption from the ImmunoGen acquisition making it more difficult to maintain business and operational relationships, the diversion of management's attention from ongoing business operations and opportunities, negative effects of the consummation of the acquisition on business or employee relationships or the market price of AbbVie's common stock and/or operating results, significant transaction costs, the assumption of unknown liabilities, the risk of litigation and/or regulatory actions related to the acquisition or ImmunoGen's business, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2022 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no obligation, and specifically declines, to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law. SOURCE AbbVie

欢迎观看重磅直播！ADC（抗体偶联药物）被誉为抗肿瘤药物中“魔法子弹”，在过去几年成为创新药研发最热的赛道。作为抗肿瘤领域的佼佼者，艾伯维早在十几年前，就开始押注ADC，先后布局过几十条管线，但大多以终止为结局。不过艾伯维没有失去对ADC的信心，近期不断加码ADC管线布局。深耕十余年自研ADC迎来曙光2013年艾伯维从雅培拆分，在纽约证券交易所挂牌上市。十年后，艾伯维成长为一家领先的制药公司，市值约2900亿美元。以修美乐（Humira，阿达木单抗）为代表的自身免疫疾病业务是艾伯维最重要的收入来源，在过去十年，修美乐给艾伯维带来超过2200亿美元的收入。然而药王终有迟暮时，随着修美乐专利到期，受生物类似药冲击，销售额持续下滑。为了弥补修美乐即将到来的下滑，艾伯维推出了两颗“超新星”：JAK抑制剂Rinvoq (upadacitinib，乌帕替尼）和 IL-23 抑制剂 Skyrizi （risankizumab，瑞莎珠单抗）。艾伯维预计到2025年，Skyrizi和Rinvoq的每年总销售额将超过175亿美元。另一方面，艾伯维在肿瘤板块不断发力。2015年，艾伯维以210亿美元收购Pharmacyclics，获得血液瘤重磅新药伊布替尼（Imbruvica）。2016年，艾伯维与罗氏合作开发白血病新药Venclexta（维奈克拉，venetoclax）在美国获批上市。Imbruvica和Venclexta组成了艾伯维血液瘤领域的基石。2020年，艾伯维与Genmab达成39亿美元合作，引进双特异性抗体药物epcoritamab以及ABBV-383，2023年5月epcoritamab（商品名：Epkinly）获得FDA批准上市，用于治疗复发或难治性弥漫性大B细胞淋巴瘤（R/R DLBCL）。多年来艾伯维一直致力于将肿瘤管线拓展至实体瘤，而被艾伯维寄予厚望的就是ADC。药智数据显示，艾伯维曾将十余个ADC管线推进至临床阶段，但多数以失败告终。2016年，艾伯维以58亿美元收购Stemcentrx，获得靶向DLL3的ADC药物Rova-T，开拓小细胞肺癌领域。遗憾的是，Rova-T疗效不佳，2019年艾伯维彻底终止了该项目。此后，艾伯维又先后放弃了多个ADC项目，包括ABBV-414（靶向EGFR）、ABBV-221（靶向EGFR）、ABBV-321（靶向EGFR）、ABBV-3373（靶向TNFα）、CX-2029（靶向CD71）、ABBV-154（靶向TNFα）、ABBV-647（靶向PTK7）、ABBV-011（靶向SEZ6）等。几番调整后，根据艾伯维最新公布的管线，目前仅有6个ADC管线，包括收购ImmunoGen所得的Elahere和IMGN-151，自研管线4个：ABBV-399 (靶向c-Met ) 、ABBV-400 (靶向c-Met ) 、ABBV-706 (靶向SEZ6 ) 、双抗ADC ABBV-969  (靶向PSMA/STEAP1)。图片来源：艾伯维官网Teliso-V (ABBV-399)c-Met蛋白的过度表达会促进肿瘤生长。但是它也是个突破点——c-Met位于肿瘤细胞表面，因此是一个非常理想的治疗靶点。例如，在非小细胞肺癌(NSCLC)患者中，近25%的患者都存在c-Met过表达。Teliso-V (ABBV-399)是艾伯维自研的一款ADC药物，该药靶向c-Met，以MMAE作为毒性有效载荷，已进入全球注册性Ⅲ期临床。2023年11月29日，艾伯维公布了Ⅱ临床LUMINOSITY顶线数据结果，该试验评估Teliso-V用以治疗c-Met蛋白过度表达、表皮生长因子受体（EGFR）野生型、晚期/转移性非鳞状非小细胞肺癌（NSCLC）患者的疗效。根据独立中心审评（ICR）分析的试验结果显示：肿瘤c-Met高度表达和中度表达患者的总缓解率分别为35%和23%。此外，其他终点显示了有意义的临床结局，包括c-Met高度表达和中度表达患者的中位缓解持续时间分别为9个月和7.2个月，中位总生存期分别为14.6个月和14.2个月。Teliso-V的安全性特征与既往结果一致，未发现新的安全性问题。艾伯维把这一结果描述为“令人信服的（compelling）”。基于该研究艾伯维计划寻求Teliso-V的加速批准，作为c-Met过表达、EGFR野生型的非鳞状非小细胞肺癌（NSCLC）患者的单药疗法。ABBV-400ABBV-400是艾伯维开发的二代c-Met ADC，有效载荷为TOP1i，用于治疗c-Met阳性实体瘤。在临床前研究中，ABBV-400在非小细胞肺癌、胃食管癌和结直肠癌的异体移植模型中表现出良好的药代动力学、体外抗增殖活性和令人信服的疗效。目前，该疗法结直肠癌(CRC)适应症已进入临床2期，肺癌和胃食管腺癌（GEA）处于临床1期。ABBV-706ABBV-706是一款靶向SEZ6的ADC，有效载荷为TOP1i，小细胞肺癌适应症正在开展1期临床试验。ABBV-969ABBV-969是一款PSMA/STEAP1双抗ADC，采用拓扑异构酶作为payload，目前公开信息不多，尚未查到临床试验信息。大手笔收购囊获first-in-class ADC管线目前艾伯维ADC自研管线虽然进展不错，但尚无上市产品。2023年11月30日，艾伯维（AbbVie）宣布收购ADC药物上市公司ImmunoGen，加码ADC管线布局。此次收购，艾伯维获得的最重要资产是一款已上市的“first-in-class” ADC药物——Elahere，用于治疗卵巢癌，使其快速进军实体瘤领域。此外，艾伯维还获得了另一款卵巢癌ADC药物IMGN-151（临床Ⅰ 期），血液瘤ADC药物Pivekimab sunirine（临床Ⅱ期），以及一款其他实体瘤ADC IMGC936（临床Ⅰ 期）。图片来源：ImmunoGen官网根据协议条款，艾伯维将以每股31.26美元的价格收购ImmunoGen的所有流通股，收购总价高达101亿美元。艾伯维和Immunogen的董事会已经通过了这项收购协议，预计收购事宜将于2024年中期完成。ImmunoGen公司成立于1981年，是最早研发ADC药物的企业之一，曾与Seagen、基因泰克并称为ADC领域的“三巨头”。ImmunoGen拥有独有的喜树碱ADC药物开发平台，旨在优化现有的喜树碱技术，以提供更宽的治疗窗，提高ADC药物的安全性和有效性。除此之外，它还构建了靶点筛选、抗体开发、毒素库、连接子库四位一体的ADC工具库。基于强大的技术平台，ImmunoGen曾与罗氏、拜耳、诺华、赛诺菲等多家国际知名制药企业展开合作。目前已有3款产品获批上市，分别为Kadcyla（HER2 ADC）、Sarclisa（ CD38 单抗）和Elahere（FRα ADC）。其中Elahere是ImmunoGen首款独立研发和商业化的ADC药物。ElahereElahere（mirvetuximab soravtansine; 索米妥昔单抗）是全球首款获批上市的FRα ADC药物，由一个binding叶酸受体的抗体、可裂解连接子和高效微观抑制剂DM4构成。该药于2022年11月获得FDA批准加速上市，治疗FRα高表达、对含铂疗法耐药的经治晚期卵巢癌患者，这也是FDA批准的首个用于铂耐药卵巢癌的ADC药物。图片来源：艾伯维官网2023年前9个月，Elahere累计销售额2.12亿美元。艾伯维认为，Elahere有着数十亿美元的市场空间，未来有望拓展早期和更大范围的卵巢癌市场。值得一提的是，2020年10月，华东医药以4000万美元预付款+2.65亿美元里程碑金额获得了该药在大中华区的独家开发和商业化权益。2023年10月，华东医药宣布ELAHERE上市许可申请获得CDE受理，此前7月，ELAHERE已被纳入国内优先审评品种名单，意味着ELAHERE有望在半年内获批。IMGN-151IMGN-151是ImmunoGen另一个重要管线，是新一代FRα靶向ADC，同样适用于卵巢癌，且具潜力扩展到其他实体瘤适应症。目前正在开展Ⅰ 期临床试验。Pivekimab sunirineImmunoGen其他管线还有靶向母细胞性浆细胞样树突状细胞肿瘤（BPDCN）的CD123靶向ADC——Pivekimab sunirine，该药物被美国FDA授予突破性疗法认定，用于治疗复发/难治性BPDCN。目前该疗法处于Ⅱ期临床。图片来源：艾伯维官网综上所述，Immunogen重点研发领域为卵巢癌ADC，包括1款已上市ADC和1款临床Ⅰ 期的ADC产品；血液瘤也有1款CD123 ADC已进入Ⅱ期临床。艾伯维认为，Immunogen研发管线与其高度互补，通过并购极大地丰富了艾伯维的肿瘤管线。而且Immunogen的ADC研发平台和开发经验，将有力地支持艾伯维推进其他ADC管线的研发进程。投资新锐寻找潜力新靶点2024年1月16日，Disco Pharmaceuticals宣布获得了艾伯维风投（AbbVieVentures）、MVentures、PanakesPartners和SofinnovaPartners等机构2000万欧元（约合2180万美元）的支持。Disco成立于2022年5月，是瑞士苏黎世联邦理工学院 (ETH) 的衍生项目。Disco认为，尽管ADC和双特异性抗体等生物制品的开发正在快速增长，但目前所有基于抗体的疗法仅靶向不到30个靶点蛋白。因此，迫切需要发现新的癌症特异性靶点和靶点对（target pair）。Disco致力于大规模解锁癌细胞的表面蛋白组（surfaceome），旨在发现新的靶点，并开发潜在“first-in-class”药物。Disco已经完成了小细胞肺癌（SCLC）的表面蛋白组图谱，并正在为SCLC开发基于抗体的治疗方法。Disco目前还在研究微卫星稳定型结直肠癌，公司的管线还包括更多未公开的项目。艾伯维加码新的技术平台，有望加速开发新一代抗肿瘤疗法。小结ADC结合了抗体的靶点特异性与化疗的杀灭功效，对多种恶性肿瘤疗效显著，成为各大药企的热门布局方向。艾伯维是最早入局ADC赛道的制药巨头之一，最早可以追溯到2008年（彼时尚未从雅培中分拆出来），十几年来屡败屡战，不过在不断地探索和试错后，近期已进入收获期。其进展最快的自研ADC项目ABBV-399已进入全球注册性3期临床，而且迭代产品ABBV-400也在稳步推进中。2023年底，艾伯维又通过收购获得了一款上市ADC产品，很快将给公司带来现金收益。而且收购ImmunoGen还能为艾伯维提供强大的ADC专业知识，加速艾伯维ADC研发进程。参考来源：DISCO Pharmaceuticals launches as thesurfaceome company with EUR 20 Millionin Seed FinancingAbbVie to Acquire ImmunoGen, includingits Flagship Cancer Therapy ELAHERE® (mirvetuximab soravtansine-gynx),ExpandingSolid Tumor PortfolioAbbVie Announces Positive Topline Resultsfrom Phase 2 LUMINOSITY Trial EvaluatingTelisotuzumab-Vedotin(Teliso-V) for Patients withPreviouslyTreated Non-Small Cell LungCancer (NSCLC)封面图来源：123rf融资超3亿美元，上市第一天，股价大涨100%！首个东南亚获批上市的国产PD-1「已起飞」直抵印尼！黑框警告，但CAR-T不凉追缉阿尔茨海默病致病元凶，人类用120年等到仑卡奈单抗点击这里，欣赏中国新药“繁花”！