Lutikizumab

作者｜灰兔子 自免药物是仅次于肿瘤药物的第二大药物市场，据弗若斯特沙利文报告，全球自身免疫疾病药物市场估计在2030年将达到1767亿美元。 如此巨大的市场也成为各大药企纷纷追逐的对象，艾伯维凭借修美乐、Skyrizi和Rinvoq位居自免冠军宝座，强生先后有Remicade、Simponi/ Simponi Aria、Stelara和Tremfya等重磅药物，罗氏有多发性硬化症重磅炸弹药物Ocrevus、赛诺菲凭借度拉普利单抗在自免领域占有重要地位，诺华有Cosentyx、Promacta/Revolade、Kesimpta和Xolair等自免重磅药物，实力不容小视。   01   艾伯维：Skyrizi有望突破110亿美元 Rinvoq Q3增长45% 10月30日，艾伯维公布2024Q3业绩，第三季度净收入同比增长3.8%至144.60亿美元。从业务板块上看，自免、肿瘤、神经科学和美容业务分别贡献70.46亿美元（+3.9%）、16.87亿美元（+11.6%）、23.63亿美元（+15.6%）、12.39亿美元（-0.1%）。 自免领域，修美乐的市场份额受到仿制药的冲击，单季度收入进一步下滑至22.27亿美元（-37.2%），其中，美国市场17.65亿美元（-41.6%），美国之外市场4.62亿美元（-12.4%）。 Skyrizi（利生奇珠单抗）和Rinvoq（乌帕替尼）是艾伯维自身免疫疾病业务中的后起之秀，正在以较高的增速填补修美乐专利悬崖的收入缺口。 Skyrizi第三季度销售额同比增长50.8%至32.05亿美元，预计全年收入可超过110亿美元。Rinvoq第三季度销售额同比增长45.3%至16.14亿美元，预计全年收入将超50亿美元。 Skyrizi最初由勃林格殷格翰研发的一种靶向炎症过程的细胞因子IL23的单抗药物，可通过与IL-23 p19亚基结合来选择性阻断IL-23。2016年，艾伯维以5.95亿美元首付款从勃林格殷格翰手中获得利生奇珠单抗的全球商业化权利。 Skyrizi于2019年4月在美国获批上市，目前获批的适应症包括银屑病、银屑病关节炎和克罗恩病等，今年6月3日，艾伯维在中国提交了利生奇珠单抗的注射液和皮下注射剂型的新的适应症申请，并且这一申请已被国家药品监督管理局药品审评中心正式接收并开始审查。推测此次提交的新适应症申请可能与溃疡性结肠炎相关。 Rinvoq（乌帕替尼）是由艾伯维研发的一款口服JAK1抑制剂，2019年8月首次在美国获批上市，用于对甲氨蝶呤应答不足或不耐受（MTX-IR）的中度至重度活动性类风湿性关节炎（RA）成人患者的治疗。 随后2022年2月，Rinvoq在中国获批上市，用于治疗成人和12岁及12岁以上青少年中重度特应性皮炎（AD）患者。目前，Rinvoq获批的适应症有类风湿性关节炎、银屑病关节炎、特应性皮炎和中度至重度溃疡性结肠炎（UC，成人）等。 除此之外，艾伯维自免领域还有很多新颖管线在研，包括口服NLRX1激动剂ABBV-113，RIPK抑制剂ABBV-668、ICOS/CD28双重抑制剂ALPN-101和 IL-1α 和 IL-1β 双变量结构域免疫球蛋白Lutikizumab等。 Lutikizumab目前处于临床2/3期，用于治疗化脓性汗腺炎（HS）和溃疡性结肠炎。 今年1月，艾伯维公布了Lutikizumab的2期结果，结果显示，既往抗 TNF 治疗失败的中度至重度HS成人患者接受 lutikizumab 300 毫克，每隔一周一次或每周 300 毫克，与安慰剂相比在第16周达到更高的HS 临床缓解（HiSCR 50） 的主要终点（59.5% vs 35.0%）。基于这些数据，艾伯维将把 lutikizumab 治疗 HS 的临床项目推进到3期（图1）[1]。 图1. Lutikizumab的2期结果   02   强生：Tremfya成功接棒 Nipocalimab自免新星 2024年10月15日，强生发布第三季度财报，Q3全球收入225亿美元，同比增长5.2%。 按业务划分，制药业务Q3营收146亿美元，同比增长4.9%，经营性同比增长6.3%，增长由肿瘤学领域的Darzalex（daratumumab）、Erleada（apalutamide）、Carvykti（ciltacabtagene autoleucel）、免疫学领域的Tremfya（古塞奇尤单抗）、神经科学领域的Spravto（艾氯胺酮）和肺动脉高压领域的Opsumit（macitentan）推动。 自身免疫药物是强生制药核心业务，主要有Stelara（乌司奴单抗）、Tremfya、Remicade（英夫利昔单抗）和Simponi/ Simponi Aria（戈利木单抗）等。 Stelara是由强生研发的首款抗IL-12/23全人源IgG1k单克隆抗体，是强生的重磅自免药物，2023年销售额首次突破百亿美元，达到108.58亿美元，但是Stelara面临专利到期问题，它的美国专利保护期已于2023年9月到期，今年销售额已经有所下滑，2024年Q3营收下降了6.6%至26亿美元。 不过好在Tremfya大有接棒Stelara之势，Tremfya是强生旗下杨森制药研发的一款靶向IL-23的p19亚基的人源化单克隆抗体，于2017年获得FDA的批准治疗中重度斑块型银屑病成人患者。 今年9月11日，Tremfya用于治疗患有中度至重度活动性溃疡性结肠炎（UC）的成人患者的新适应症获得FDA批准上市，这是一种结肠内壁发炎的慢性大肠疾病。Tremfya是第一个也是唯一一个获批的全人源双效单克隆抗体，可阻断 IL-23，同时还能结合 CD64，CD64 是产生 IL-23 的细胞上的受体[2]。 2021年Tremfya销售额首次突破20亿美元，2022销售额达到26.68亿美元，2023年销售额同比增长17.9%至31.47亿美元，今年前三个季度销售额已达到27.14亿美元，近期获批的UC新适应症有望进一步提升其销售额。 除此之外，强生的另一款自免药物nipocalimab表现出很大的潜力，nipocalimab是强生以65亿美元从Momenta公司引进的一款FcRn单抗药物。 Nipocalimab的2期DAHLIAS研究结果显示中度至重度干燥症患者（SjD）在接受nipocalimab治疗后，疾病活动的关键指标有所改善，并且IgG显著减少了77%以上。 根据2期DAHLIAS研究的结果，Nipocalimab被授予美国FDA突破性疗法认定（BTD），用于治疗患有中度至重度干燥症的成人患者，这是一种具有高患病率的使人衰弱且慢性自身抗体疾病，目前尚无批准的先进治疗方法可用（图2）[3]。 图2. Nipocalimab被授予美国FDA突破性疗法认定（BTD） Nipocalimab是唯一在SjD中获得此称号的研究疗法。此次是Nipocalimab第二次获得突破性疗法认定，第一次是2月Nipocalimab被批准用于治疗患有严重胎儿和新生儿溶血性疾病（HDFN）高风险的同种异体免疫孕妇。   03   罗氏：Ocrevus皮下注射剂获批 Xolair老药新用 10月23日，罗氏公布三季度报，前九个月，制药业务销售额 343 亿瑞士法郎（387.6亿美元，按1瑞士法郎=1.13美元计算），增长 7%，基础业务（不包括 COVID-19）增长 9%；第三季度，实现销售额增长 9%（以瑞士法郎计算为 6%），与第二季度持平。 其中制药业务的增长主要得益于 Vabysmo（严重眼病）、Phesgo（乳腺癌）、Ocrevus（多发性硬化症）、Hemlibra（血友病）和 Polivy（血癌）销售额的增长。 罗氏主要自免产品有CD20单抗Ocrevus、IL-6单抗Actemra/RoActemra和IgE单抗Xolair等。 Ocrevus是由罗氏研发的的靶向CD20的重磅抗体疗法，是第一个也是唯一一个复发性或原发性进行性多发性硬化症（RMS或PPMS）患者都有益的多发性硬化症疾病改善治疗（DMT），于2017年在美国获批上市。 今年9月，FDA基于3 期OCARINA II 试验数据批准 Ocrevus Zunovo™（奥瑞珠单抗和透明质酸酶-ocsq）皮下注射用于治疗成人复发型多发性硬化症 (MS)，包括临床孤立综合征、复发缓解型多发性硬化症和活动性继发性进展型多发性硬化症；以及成人原发性进展型 MS。 Ocrevus Zunovo 是针对 CD20 的溶细胞抗体奥瑞珠单抗和透明质酸酶-ocsq（一种可增加皮下 (SC) 组织通透性的内切糖苷酶）的组合。该产品每年给药两次，每次10分钟，皮下注射。 Ocrevus目前罗氏最畅销药物，今年前九个月销售额达到50.56亿瑞士法郎（57.13亿美元），同比增长9%（图3）[4]。 图3. 罗氏2024Q3销售额前三药物 Actemra/RoActemra最初由Chugai研发，后与罗氏共同开发和销售的可以结合sIL-6R和mIL-6R的单抗药物，先后于2005年、2009年、2010年和2013年在日本、欧盟、美国和中国获批上市，用于治疗类风湿关节炎（RA）等。 Actemra/RoActemra的销售额于2017年首次突破20亿美元，随后一直稳定增长，由于新冠期间，托珠单抗被纳入中国新冠治疗指南，销售额2021年达到39.6亿美元，不过随着新冠影响减弱以及专利到期等原因，Actemra/RoActemra销售额近两年开始下降，2023年销售额为26.3亿瑞士法郎（29.7亿美元），今年前九个月销售额19.48亿瑞士法郎（22亿美元）。 Xolair是由罗氏和诺华研发的靶向和阻断IgE的抗体药物。通过降低游离IgE，下调高亲和力IgE受体和限制肥大细胞脱颗粒，Xolair在整个过敏性炎症级联过程中最大限度地减少介质的释放。 Xolair是一款老药，首次于2003年6月被FDA批准皮下注射用于治疗12岁及以上的中度至重度持续性哮喘，虽然Xolair在中美的专利已到期，但凭借不断获批的新适应症，如今年2月，Xolair获得美国FDA获批上市用于治疗成人和1岁以上儿童因意外暴露于一种或多种食物而可能发生免疫球蛋白E（IgE）介导的过敏反应。该获批就是基于OUtMATCH研究的积极数据。值得一提的是，这是FDA批准的首款也是唯一一款用于减少一种或多种食物过敏反应的药物。 随着新适应症的获批，Xolair的销售额依然可观，据罗氏财报，Xolair前9个月销售额为17.37亿瑞士法郎（19.63亿美元）。 除此之外，罗氏在免疫领域还布局了用于治疗多发性硬化症的BTK抑制剂Fenebrutinib、用于治疗溃疡性结肠炎的TL1A单抗RG6631等。 Fenebrutinib是由罗氏研发的一款口服可逆且非共价BTK抑制剂，可以阻断小胶质细胞Fc γ受体（FcγR）激活的有害作用，包括细胞因子和趋化因子的释放、小胶质细胞聚集和不同人脑细胞系统中的神经突损伤（图4）[5]。 图4. fenebrutinib 对 B 细胞和小胶质细胞通路的影响示意图 9月4日，罗氏公布Fenebrutinib的2期FENopta开放标签扩展（OLE）研究的最新结果。结果显示，接受Fenebrutinib长达1年治疗的复发性多发性硬化症（RMS）患者保持非常低的疾病活动水平，并且残疾状况没有进展。   04   赛诺菲：度普利尤单抗扛起大旗 有望突破130亿欧元 2024年10月25日，赛诺菲发布了2024年第三季度财务业绩。2024年第三季度（报告期），公司收入134.38亿欧元（约141.64亿美元，按1欧元=1.054美元计算），同比增长15.7%（按固定汇率计算，下同）。 制药业务增长强劲，收入121.67亿欧元（约137.49亿美元），同比增长16.6%，主要由度普利尤单抗和疫苗驱动。 度普利尤单抗是赛诺菲的重磅自免药物，是一款靶向IL-4R的免疫球蛋白G4亚类的全人源单克隆抗体，相继于2017年3月和2020年6月在美国和中国获批上市，成为首个治疗中重度特应性皮炎的生物制剂。 度普利尤单抗自获批以来销售额逐年上升，2023年销售额达到107.15亿欧元（约121.08亿美元），主要得益于特应性皮炎、哮喘、慢性鼻-鼻窦炎伴鼻息肉）、结节性痒疹和嗜酸性粒细胞性食管炎（EoE）临床需求的持续释放。今年Q3销售额达到34.76亿欧元（约39.28亿美元），加上今年上半年的61.38亿欧元（约69.36亿美元），前九个月销售额已达到96.14亿欧元（约108.64亿美元），全年有望突破赛诺菲先前定下的130亿欧元销售目标（图5）。 图5. 度普利尤单抗销售额 今年度普利尤单抗也取得很多进展，如7月3日，度普利尤单抗获欧洲药品管理局（EMA）批准作为以血嗜酸性粒细胞水平升高为特征的不受控制的慢性阻塞性肺疾病（COPD）患者的附加维持治疗，包括已经联合使用吸入性皮质类固醇（ICS）、长效β2受体激动剂（LABA）和长效毒蕈碱拮抗剂（LAMA）的患者。 9月27日，赛诺菲美国FDA和中国NMPA已批准度普利尤单抗作为COPD控制不佳且嗜酸性粒细胞性表型成人的附加维持治疗。 度普利尤单抗是美国批准用于治疗这些患者的第一种生物药物。FDA 的批准基于两项具有里程碑意义的关键3期研究（BOREAS和NOTUS）的数据：它们达到了在52周内中度或重度 COPD 恶化的年化率降低30%和34%的主要终点。 与安慰剂相比，第12周时支气管扩张剂后FEV1较基线改善74mL和68mL，持续52周。在关键次要终点12周和52周时，支气管扩张剂前FEV1较基线观察到相似幅度的统计学显着改善[6]。 11月6日，赛诺菲宣布欧洲药品管理局已批准度普利尤单抗用于治疗年仅 1岁儿童的嗜酸性粒细胞性食管炎（EoE）。具体来说，该批准涵盖1至11岁、体重至少15公斤且受常规药物治疗控制不充分、不耐受或不适合常规药物治疗的儿童。这扩大了欧盟对成人和青少年 EoE 的初步批准，并使度普利尤单抗成为第一个也是唯一一个用于治疗这些年轻患者的药物[7]。 11月15日，赛诺菲宣布美国FDA已接受重新提交度普利尤单抗的补充生物制品许可申请（sBLA）以供审查，用于治疗 H1 抗组胺药治疗无法充分控制的慢性自发性荨麻疹（CSU）成人和 12 岁及以上儿童患者。FDA 决定的目标行动日期为2025年4月18日。 除了靶向IL-4R的度普利尤单抗之外，赛诺菲还有多款自免药物处于临床开发阶段，包括靶向IL-33的单抗Itepekimab、CD40L单抗frexalimab、BTK抑制剂tolebrutinib和rilzabrutinib以及OX40L单抗amlitelimab等。 Itepekimab是由赛诺菲研发的“First-in-class”靶向IL-33的一种人IgG4单克隆抗体，通过作用于IL-33减少气道炎症并预防ILC2细胞的激活。这可能有助于减轻哮喘症状并改善肺功能。 Frexalimab最初是由ImmuNext研发的是一种靶向CD40L的新型单克隆抗体，2017年，赛诺菲和ImmuNext签订一项全球独家授权协议，获得Frexalimab在狼疮和多发性硬化症等一系列自身免疫性疾病领域的开发权益。为此，赛诺菲将向ImmuNext支付的潜在里程碑付款总额可能会达到5亿美元，以及高达两位数的产品销售额分级特许权使用费。 Amlitelimab最初由Kymab研发的一款全人源的OX40L单抗，通过靶向OX40配体，amlitelimab旨在恢复促炎T细胞和调节性T细胞之间的免疫稳态。 2021年11月，赛诺菲与Kymab达成协议，以14.5亿美元的价格收购了Kymab，将Amlitelimab收入囊中，Amlitelimab有可能成为一系列免疫介导的疾病和炎症性疾病（包括中度至重度特应性皮炎和哮喘）的首创治疗方法。   05   诺华：Cosentyx同比增长28% Fabhalta后起之秀 10月29日，诺华公布2024年第三季度业绩，公司实现营收128亿美元，超出市场预期的118亿美元，较去年同期增长10%（按固定汇率计算）；公司总净收入32 亿美元，较去年同期增长121%。 其中，核心业务收入51 亿美元，同比增长20%，主要得益于Entresto (+26%)、Cosentyx (+28%)、Kisqali (+43%)、Kesimpta (+28%)、Pluvicto (+50%) 和 Leqvio (+119%)等产品销量的增长。 诺华免疫领域拥有重磅药物Cosentyx、Promacta/Revolade、Kesimpta、 Xolair和Fabhalta等。 Cosentyx是由诺华研发的一款能够靶向IL-17A单抗药物，相继于2016年3月和2019年4月在美国和中国获批上市，目前获批的适应症有银屑病关节炎（PsA）、斑块型银屑病（PsO）、强直性脊柱炎（AS）和活动性幼年银屑病关节炎（JPsA）等。 Cosentyx自批准以来销售额稳步增加，2018年销售额达到28.37亿美元，2021年销售额超过40亿美元，达到47.18亿美元，2022年高达47.88亿美元，2023年销售额达到49.8亿美元，今年第三季度销售额为16.93亿美元（图6），至此前九个月销售额达到45.45亿美元。 图6. Cosentyx销售额 Revolade（欧洲/印度版）/Promacta（美国版）最初由GSK公司研发的一种小分子的血小板生成素受体激动剂（TPO-RA），在2014年，诺华通过与GSK的资产置换交易获得该产品。 Revolade/Promacta相继于2008年11月和2017年12月在美国和中国上市，用于治疗慢性免疫性血小板减少症（ITP）。 Revolade/Promacta全球销售额于2018年突破10亿美元，进入重磅炸弹药行列，2019年为14.16亿美元，同比增长21%。2020年全球销售额达到17.38亿美元，同比增长22.74%，2021年销售额达到20.16亿美元，2022年20.88亿美元，2023年销售额22.69亿美元。 Kesimpta (奥法妥木单抗)是由诺华研发的靶向CD20单抗，于2009年获批用于治疗慢性淋巴细胞白血病，后于2020年8月获得美国FDA批准，作为皮下注射剂，用于治疗成人复发型多发性硬化症（RMS），此后，随着自免领域的适应症批准，Kesimpta销量额开始激增。 2022年Kesimpta销售额同比增长194%至10.92亿美元，2023年Kesimpta销售额同比增长99%至21.71亿美元。 Fabhalta （iptacopan）是由诺华研发的一种补体B因子抑制剂，可在免疫系统的替代补体途径中发挥近端作用，全面控制血管内外的红细胞 (RBC) 破坏。 2023年12月5日，Fabhalta首次获得FDA批准上市，作为首个口服单药疗法，用于治疗阵发性夜间血红蛋白尿症（PNH）成人患者。在临床试验中，使用 Fabhalta治疗可提高大多数患者的血红蛋白水平（在不输注红细胞的情况下，血红蛋白水平比基线值≥ 2g/dL），在 APPLY-PNH 试验中，几乎所有接受 Fabhalta 治疗的患者都没有输血。 除此之外，诺华在临床上布局的免疫管线多达26项，包括临床1期的IPX643、MHV370、PIT565，临床2期的iscalimab、DFV890以及临床3期的remibrutinib 、ianalumab等（图7）。  图7. 诺华临床管线汇总 Ianalumab是由诺华研发的一款抗BAFF-R全人源单克隆抗体，靶向B细胞，可与B细胞活化因子受体（BAFF-R）结合，目前处于临床3期，用于治疗干燥综合征、狼疮性肾炎和系统性红斑狼疮。   小结   各大药企在自免领域都有重磅产品，未雨绸缪，防止重磅产品专利到期引起销售额断崖式下降，各大药企纷纷发力，后续布局很多自免管线，给更多患者带来更多的选择。 参考文献 1. Lutikizumab Showed Positive Results in a Phase 2 Trial of Adults with Moderate to Severe Hidradenitis Suppurativa as Program Advances to Phase 3 2. TREMFYA® (guselkumab) receives U.S. FDA approval for adults with moderately to severely active ulcerative colitis, strengthening Johnson & Johnson’s leadership in inflammatory bowel disease 3. Nipocalimab demonstrates significant clinical improvement in disease activity and IgG reduction in Phase 2 Sjögren’s disease study 4.https://assets.roche.com/f/176343/x/f7a9170178/231024_mr_q3_roche-2024_en.pdf 5. Julie Langlois et.al, Fenebrutinib, a Bruton’s tyrosine kinase inhibitor, blocks distinct human microglial signaling pathways, Journal of Neuroinflammation (2024) 21:276 6. Press Release: Dupixent approved in the US as the first-ever biologic medicine for patients with COPD7. Press Release: Dupixent approved in the EU as the first and only medicine for young children with eosinophilic esophagitis 共建Biomedical创新生态圈！ 如何加入BiG会员？

Reports Third-Quarter Diluted EPS of $0.88 on a GAAP Basis, a Decrease of 12.0 Percent; Adjusted Diluted EPS of $3.00, an Increase of 1.7 Percent; These Results Include an Unfavorable Impact of $0.04 Per Share Related to Acquired IPR&D and Milestones Expense Delivers Third-Quarter Net Revenues of $14.460 Billion, an Increase of 3.8 Percent on a Reported Basis or 4.9 Percent on an Operational Basis Third-Quarter Global Net Revenues from the Immunology Portfolio Were $7.046 Billion, an Increase of 3.9 Percent on a Reported Basis, or 4.8 Percent on an Operational Basis; Global Humira Net Revenues Were $2.227 Billion; Global Skyrizi Net Revenues Were $3.205 Billion; Global Rinvoq Net Revenues Were $1.614 Billion Third-Quarter Global Net Revenues from the Oncology Portfolio Were $1.687 Billion, an Increase of 11.6 Percent on a Reported Basis, or 13.0 Percent on an Operational Basis; Global Imbruvica Net Revenues Were $828 Million; Global Venclexta Net Revenues Were $677 Million Third-Quarter Global Net Revenues from the Neuroscience Portfolio Were $2.363 Billion, an Increase of 15.6 Percent on a Reported Basis, or 16.0 Percent on an Operational Basis; Global Botox Therapeutic Net Revenues Were $848 Million; Global Vraylar Net Revenues Were $875 Million; Combined Global Ubrelvy and Qulipta Net Revenues Were $445 Million Third-Quarter Global Net Revenues from the Aesthetics Portfolio Were $1.239 Billion, a Decrease of 0.1 Percent on a Reported Basis, or an Increase of 1.8 Percent on an Operational Basis; Global Botox Cosmetic Net Revenues Were $671 Million; Global Juvederm Net Revenues Were $258 Million Successfully Completed Acquisition of Cerevel, Adding Pipeline of Highly Complementary Assets to AbbVie's Existing Neuroscience Portfolio Raises 2024 Adjusted Diluted EPS Guidance Range from $10.67 - $10.87 to $10.90 - $10.94, which Includes an Unfavorable Impact of $0.64 Per Share Related to Acquired IPR&D and Milestones Expense Incurred Year-To-Date Through the Third Quarter 2024 Announces 2025 Dividend Increase of 5.8 Percent, Beginning with Dividend Payable in February 2025 NORTH CHICAGO, Ill., Oct. 30, 2024 /PRNewswire/ -- AbbVie (NYSE:ABBV) announced financial results for the third quarter ended September 30, 2024. "We delivered another quarter of strong commercial execution and significant pipeline progress," said Robert A. Michael, chief executive officer, AbbVie. "Based upon the momentum of AbbVie's business and our confidence in the long-term growth outlook, we are once again raising our full-year guidance and are increasing our quarterly dividend." Third -Quarter Results Worldwide net revenues were $14.460 billion, an increase of 3.8 percent on a reported basis, or 4.9 percent on an operational basis. Global net revenues from the immunology portfolio were $7.046 billion, an increase of 3.9 percent on a reported basis, or 4.8 percent on an operational basis. Global Humira net revenues of $2.227 billion decreased 37.2 percent on a reported basis, or 36.5 percent on an operational basis. U.S. Humira net revenues were $1.765 billion, a decrease of 41.6 percent. Internationally, Humira net revenues were $462 million, a decrease of 12.4 percent on a reported basis, or 7.8 percent on an operational basis. Global Skyrizi net revenues were $3.205 billion, an increase of 50.8 percent on a reported basis, or 51.5 percent on an operational basis. Global Rinvoq net revenues were $1.614 billion, an increase of 45.3 percent on a reported basis, or 47.4 percent on an operational basis. Global net revenues from the oncology portfolio were $1.687 billion, an increase of 11.6 percent on a reported basis, or 13.0 percent on an operational basis. Global Imbruvica net revenues were $828 million, a decrease of 8.8 percent, with U.S. net revenues of $618 million and international profit sharing of $210 million. Global Venclexta net revenues were $677 million, an increase of 14.8 percent on a reported basis, or 18.2 percent on an operational basis. Global Elahere net revenues were $139 million. Global net revenues from the neuroscience portfolio were $2.363 billion, an increase of 15.6 percent on a reported basis, or 16.0 percent on an operational basis. Global Botox Therapeutic net revenues were $848 million, an increase of 13.4 percent on a reported basis, or 14.4 percent on an operational basis. Global Vraylar net revenues were $875 million, an increase of 16.6 percent. Global Ubrelvy net revenues were $269 million, an increase of 15.3 percent. Global Qulipta net revenues were $176 million, an increase of 33.6 percent. Global net revenues from the aesthetics portfolio were $1.239 billion, a decrease of 0.1 percent on a reported basis, or an increase of 1.8 percent on an operational basis. Global Botox Cosmetic net revenues were $671 million, an increase of 8.2 percent on a reported basis, or 9.9 percent on an operational basis. Global Juvederm net revenues were $258 million, a decrease of 19.7 percent on a reported basis, or 16.9 percent on an operational basis. On a GAAP basis, the gross margin ratio in the third quarter was 70.9 percent. The adjusted gross margin ratio was 84.4 percent. On a GAAP basis, selling, general and administrative (SG&A) expense was 29.1 percent of net revenues. The adjusted SG&A expense was 23.0 percent of net revenues. On a GAAP basis, research and development (R&D) expense was 14.7 percent of net revenues. The adjusted R&D expense was 14.2 percent of net revenues. Acquired IPR&D and milestones expense was 0.6 percent of net revenues. On a GAAP basis, the operating margin in the third quarter was 26.5 percent. The adjusted operating margin was 46.7 percent. Net interest expense was $591 million. On a GAAP basis, the tax rate in the quarter was 25.0 percent. The adjusted tax rate was 16.2 percent. Diluted EPS in the third quarter was $0.88 on a GAAP basis. Adjusted diluted EPS, excluding specified items, was $3.00. These results include an unfavorable impact of $0.04 per share related to acquired IPR&D and milestones expense. Note: "Operational" comparisons are presented at constant currency rates that reflect comparative local currency net revenues at the prior year's foreign exchange rates. Recent Events AbbVie announced that it completed its acquisition of Cerevel, adding a pipeline of highly complementary assets to AbbVie's existing neuroscience portfolio. Cerevel's pipeline includes emraclidine, a potential best-in-class, next-generation antipsychotic, that is being studied for the treatment of schizophrenia; tavapadon, a first-in-class dopamine D1/D5 selective partial agonist for the management of Parkinson's disease (PD); as well as CVL-354, a potential best-in-class kappa opioid receptor (KOR) antagonist being studied for the treatment of major depressive disorder (MDD). Cerevel is a strong strategic fit for AbbVie and has potential to meaningfully impact revenue into the next decade. AbbVie announced positive topline results from its pivotal Phase 3 TEMPO-1 trial evaluating tavapadon as a fixed-dose monotherapy treatment in early PD. In the study, tavapadon met the primary endpoint, demonstrating a statistically significant improvement from baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III combined score at week 26. Tavapadon also met the key secondary endpoint, demonstrating statistically significant improvement from baseline in the MDS-UPDRS Part II score. Full results from the TEMPO-1 study will be submitted for presentation at future medical meetings and used to support regulatory submissions of tavapadon as a treatment for PD. Topline results from TEMPO-2, the Phase 3 flexible-dose monotherapy trial for tavapadon, are expected by the end of 2024. AbbVie announced the U.S. Food and Drug Administration (FDA) approved Vyalev (foscarbidopa and foslevodopa) as the first subcutaneous 24-hour infusion of levodopa-based therapy for the treatment of motor fluctuations in adults with advanced PD. The approval was supported by results from a pivotal Phase 3 head-to-head, randomized and controlled clinical trial that demonstrated a statistically significant improvement in "on" time without troublesome dyskinesia and decreased "off" time, compared to oral immediate-release carbidopa/levodopa (CD/LD). AbbVie and Aliada Therapeutics announced a definitive agreement under which AbbVie will acquire Aliada, a biotechnology company advancing therapies using a novel blood-brain barrier (BBB)-crossing technology to address challenging central nervous system (CNS) diseases. Aliada's lead investigational asset utilizing this delivery technology, ALIA-1758, is an anti-pyroglutamate amyloid beta (3pE-Aβ) antibody in development for the treatment of Alzheimer's disease (AD). The acquisition also allows AbbVie to utilize Aliada's novel BBB-crossing technology to enhance discovery and development efforts across neuroscience. AbbVie and Gedeon Richter announced a new discovery, co-development and license agreement to advance novel targets for the potential treatment of neuropsychiatric conditions. This collaboration expands upon the success of nearly two decades of partnership on CNS projects. AbbVie announced the European Commission (EC) approved Skyrizi (risankizumab) for the treatment of adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response, lost response, or were intolerant to conventional or biologic therapy. The approval was supported by data from two pivotal Phase 3 trials in which Skyrizi achieved the primary endpoint of clinical remission as well as key secondary endpoints. This marketing authorization for Skyrizi marks its fourth approved indication in the European Union (EU). Skyrizi is part of a collaboration between Boehringer Ingelheim and AbbVie, with AbbVie leading development and commercialization globally. At the European Academy of Dermatology and Venerology (EADV) Congress 2024, AbbVie shared more than 30 presentations that showcased the depth and strength of AbbVie's dermatology portfolio. Presentations highlighted data for Rinvoq (upadacitinib), Skyrizi and lutikizumab across a multitude of dermatological conditions. AbbVie announced that the EC granted conditional marketing authorization for Tepkinly (epcoritamab) as a monotherapy for the treatment of adult patients with relapsed or refractory (r/r) follicular lymphoma (FL) after two or more lines of prior therapy. Tepkinly is the first subcutaneous bispecific antibody conditionally approved as a monotherapy in the EU to treat both r/r FL and r/r diffuse large B-cell lymphoma (DLBCL), after two or more lines of prior therapy. The EC approval is supported by data from the Phase 1/2 EPCORE NHL-1 clinical trial, which evaluated the safety and efficacy of Tepkinly in adult patients with r/r FL. Tepkinly is being co-developed by AbbVie and Genmab. AbbVie announced the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending the marketing authorization of Elahere (mirvetuximab soravtansine) for the treatment of adult patients with folate receptor alpha (FRα)-positive, platinum-resistant and high-grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer who have received one to three prior treatment regimens. The CHMP's opinion is supported by results of the Phase 3 MIRASOL clinical trial and the EC decision on this indication for Elahere is anticipated later this year. AbbVie announced submission of a Biologics License Application (BLA) to the FDA for accelerated approval (AA) of Teliso-V (telisotuzumab vedotin) in adult patients with previously treated, locally advanced or metastatic epidermal growth factor receptor (EGFR) wild type, nonsquamous non-small cell lung cancer (NSCLC) with c-Met protein overexpression. The BLA is supported by data from the Phase 2 LUMINOSITY clinical trial and review of the BLA will be conducted under FDA's Oncology Center of Excellence (OCE) Real-Time Oncology Review (RTOR) program. There are currently no approved anti-cancer therapies specifically for c-Met overexpressing NSCLC and if approved, Teliso-V would be the first-in-class therapy for this patient population. At the European Society for Medical Oncology (ESMO) Congress 2024, AbbVie showcased new data from its innovative antibody-drug conjugate (ADC) platform in tumor types with high unmet needs. Highlights included full data from the primary analysis of the positive, single-arm Phase 2 PICCOLO trial, evaluating Elahere for high FRα expressing platinum-sensitive ovarian cancer (PSOC); patient reported outcomes from the Phase 2 LUMINOSITY trial, evaluating Teliso-V in advanced NSCLC; as well as new safety and efficacy data in pre-treated patients with advanced NSCLC and gastroesophageal (GEA) cancer, from a Phase 1 study of ABBV-400 (telisotuzumab adizutecan). Allergan Aesthetics announced the FDA approved Botox Cosmetic (onabotulinumtoxinA) for temporary improvement in the appearance of moderate to severe vertical bands connecting the jaw and neck (platysma bands) in adults. Botox Cosmetic is the first product with four aesthetic indication areas: forehead lines, frown lines, crow's feet lines, and now platysma bands, making it the first product of its kind to go beyond the face. Allergan Aesthetics announced the launch of Botox Cosmetic for the treatment of masseter muscle prominence (MMP) in China. The approval is supported by Botox Cosmetic's well-established safety profile as well as clinical trial data that demonstrated Botox Cosmetic is effective in reducing the prominence of the masseter muscle. Botox Cosmetic is the first neurotoxin approved in China for MMP, the largest global MMP market. Allergan Aesthetics intends to develop Botox Cosmetic treatment for MMP in additional global markets and expand the use of Botox Cosmetic in the lower face. At the American Society for Dermal Surgery (ASDS), Allergan Aesthetics presented a total of 12 abstracts that showcased its commitment to patient outcomes and detailed insights and understanding of key concerns across differentiated patient segments. Highlights included four Best of Cosmetic Abstracts as well as a panel discussion on the impact of social media on patient experience and expectations when considering aesthetic treatment. Full-Year 2024 Outlook AbbVie is raising its adjusted diluted EPS guidance for the full year 2024 from $10.67 - $10.87 to $10.90 - $10.94, which includes an unfavorable impact of $0.64 per share related to acquired IPR&D and milestones expense incurred year-to-date through the third quarter 2024. The company's 2024 adjusted diluted EPS guidance excludes any impact from acquired IPR&D and milestones that may be incurred beyond the third quarter of 2024, as both cannot be reliably forecasted. Any potential IPR&D and milestones expense related to the recently announced acquisition of Aliada Therapeutics is also excluded from AbbVie's 2024 adjusted diluted EPS guidance, as the transaction is expected to close in the fourth quarter of 2024. Company Declares Dividend Increase of 5.8 Percent AbbVie is announcing today that its board of directors declared an increase in the company's quarterly cash dividend from $1.55 per share to $1.64 per share beginning with the dividend payable on February 14, 2025 to shareholders of record as of January 15, 2025. This reflects an increase of approximately 5.8 percent, continuing AbbVie's strong commitment to returning cash to shareholders through a growing dividend. Since the company's inception in 2013, AbbVie has increased its quarterly dividend by 310 percent. AbbVie is a member of the S&P Dividend Aristocrats Index, which tracks companies that have annually increased their dividend for at least 25 consecutive years. About AbbVie AbbVie's mission is to discover and deliver innovative medicines 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 across our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at . Follow @abbvie on X (formerly Twitter), Facebook, Instagram, YouTube or LinkedIn. Conference Call AbbVie will host an investor conference call today at 8:00 a.m. Central Time to discuss our third-quarter performance. The call will be webcast through AbbVie's Investor Relations website at investors.abbvie.com. An archived edition of the call will be available after 11:00 a.m. Central Time. Non-GAAP Financial Results Financial results for 2024 and 2023 are presented on both a reported and a non-GAAP basis. Reported results were prepared in accordance with GAAP and include all revenue and expenses recognized during the period. Non-GAAP results adjust for certain non-cash items and for factors that are unusual or unpredictable, and exclude those costs, expenses, and other specified items presented in the reconciliation tables later in this release. AbbVie's management believes non-GAAP financial measures provide useful information to investors regarding AbbVie's results of operations and assist management, analysts, and investors in evaluating the performance of the business. Non-GAAP financial measures should be considered in addition to, and not as a substitute for, measures of financial performance prepared in accordance with GAAP. 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, 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 2023 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its Quarterly Reports on Form 10-Q and in other documents that AbbVie subsequently files with the Securities and Exchange Commission that update, supplement or supersede such information. 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 WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED