Mirikizumab

1整体表现LLY在连续两个季度不及预期造成的股价大跌之后，原本依靠Orforglipron的临床读出形成了一波强力反弹到$800b以上，然而这个季报一出瞬间又掉到$750b。一季度收入同比增长45%，净利润同比增长29%，虽然看起来增收不增利，不过这里要考虑到收购Scorpion的每股$1.72的IPR&D负面影响，其实利润增长相当够看。自从24Q4美欧日市场均价下降后，这个季度的降价幅度继续扩大，看起来以价换量带来了效果，销量同比增长飞快，主要都来自Mounjaro的增长；而中国的Mounjaro上市后因供货短缺尚未放量，公司预计将在25H2增加供应。在2024年指引过于激进而错失后，公司2025年初的指引就已经相对理性，而这个季度的指引更新中，收入预期维持在$58-61b、也说明公司认为本季度表现符合预期，而利润预期因收购的IPR&D影响略有下调。2Tirzepatide众所周知，笔者长期以GLP1“吹哨人”自居（参见我是不是可以自称GLP1“吹哨人”了？），自然要不停审视这一观点的可靠性，同时随时做好自我打脸的准备。Tzp这个季度实现了$6.2b销售额，同比增速165%看似固然势不可挡，而环比增速13%基本坐实了逐步走平的预期。拆细来看，Mounjaro在美国市场的增长几乎已经触顶，近几个季度的增长主要依靠Mounjaro在欧日以及Zepbound来驱动。在与Sema的角力中，Tzp已经全面占据上风（这一趋势早在24年初就已明朗，参见【医苑观畴】2024年一季度海外药企进展更新：礼来LLY）。在T2D市场，Tzp的总处方量和新处方量份额分别达到39%和46%，正式完成对Sema的逆转；在减肥市场，Tzp的总处方量和新处方量份额更是分别高居60%和74%，形成对Sema的碾压之势。于是，GLP-1市场已经正式从双寡头齐头并进跑马圈地，向Tzp蚕食Sema份额的状态过渡，这对于高速增长的赛道而言应该是一个引起高度重视的前置信号。甚至对于LLY反复提及的Zepbound Vial剂型，确实在推动处方量提升和争抢份额中起了积极作用（须注意的是上图处方量增长应有相当一部分恰是vial贡献），但对整个市场空间而言也未见得是多么重大的正面作用，毕竟只有在看到增量边界的情况下才会注重存量优化。面对攻守易型，NVO不得不率先变阵、而且很鸡贼地选择就卡在两家公司公布季报之前官宣，包括CVS Caremark决定将Wegovy作为首选GLP-1药物、以及与Hims&Hers达成合作等，这也是导致LLY当天大跌的最直接因素。对此，管理层在电话会上面对汹涌而来的提问，并没有给出任何令人信服的策略（当然要考虑到给他们的反应时间太短），特别是对于是否会做出应对性的降价、乃至进入价格战，基本都不置可否，摆出了一副“别慌我们能赢”“对手先乱所以优势在我”“我有Orfo我怕谁”的姿态。那么就带来一个问题，GLP1市场是否确实接近天花板、乃至即将陷入价格绞杀的阶段呢？笔者目前仍维持谨慎悲观的态度，至少近几个季度从两家巨头的言行来看，已经不复一年前的星辰大海之态。3其他已上市产品在Tirzepatide历史级的增长面前，似乎讨论LLY的业绩就只需要关注这个单品，而我们同时也应注意到，整个公司其他产品线的表现也相当可圈可点，除了Dulaglutide属于内部自我迭代以外，主力品种几乎全都处在成长轨道，特别是诸如Abemaciclib和Empagliflozin等的增量贡献放在全市场来看也已经处于顶流水平（毕竟有很多MNC的最大单品在LTM也拿不出$1b以上的增量）。除了Tzp以外，这样全面和坚实的成长性，才是LLY值得高估值青睐的核心原因。除了Tzp以外的其他代谢基本盘中，Empagliflozin的惊艳还在持续，单季突破$1b大关、LTM累计达到$3.4b。肿瘤板块可能会成为较早进入增长放缓的产品线，Abemaciclib在刨掉年底年初的库存影响后已经基本走平，单季维持在$1.3b上下，市场份额也开始下滑；BTK C481S抑制剂Pirtobrutinib爬坡也相当乏力，单季仍然挣扎在$100m上下。自免板块基本维持着此前的趋势，IL-17A单抗Ixekizumab维持爬坡态势（刨去年底年初的存货影响），LTM累计超过$3.4b，仍在同靶点霸主Secukinumab的50%左右；不过剩下确实难成气候，JAK抑制剂Baricitinib看起来都很难上$1b了、与隔壁Upadacitinib的差距越拉越大，新晋的Lebrikizumab和Mirikizumab的爬坡还需要更多时间。其他唯一的看点CGRP单抗Galcanezumab本季度突然被腰斩，连带着对整个偏头痛市场的空间都要打问号；而万众瞩目的Aβ单抗Donanemab，上市后第三个季度只爬到$22m，总让人怀疑这几十年和几百亿是不是值得……4在研管线近期LLY与NVO双雄争霸的局面逆转，除了Tzp对Sema以外，更多是GLP-1领域的后续管线呈现一枯一荣。与隔壁的Amylin铩羽相比（参见【药海听涛】Amylin这是刚火就要凉了？CagriSema公布第二个临床三期结果），LLY可谓春风得意，小分子Orforglipron读出了首个三期临床ACHIEVE-1试验的积极结果：在559例T2D换着中，给药40周后，Orfo的36/12/3mg剂量组与安慰剂组相比，A1c警服分别为1.5%/1.6%/1.3%/0.1%，体重降幅则分别为7.9%/6.1%/4.7%/1.6%、且尚未达到减重平台期；安全性方面，四个组的腹泻发生率26%/21%/19%/9%、恶心发生率16%/18%/13%/2%、因AE而停药比例8%/4%/6%/1%，未观察到肝脏毒性，应该说是在预期范围内。公司宣布，将在25年底前向提交减重的NDA，在26年提交T2D的NDA，给NVO施加的压迫感简直拉满。不过在Tzp的重要适应症HFpEF上，LLY遭遇了与NVO类似的情况，将24年11月提交该适应症上市申请撤回，看起来FDA要求补充临床试验（虽然公司表示可能可以由其他试验提供数据），这样本以为在这个适应症上相对Sema的优势又被拉回来了。除了GLP-1，代谢管线也进展频频，继上个季度小分子Lp(a)抑制剂Muvalaplin的二期读出后，同靶点siRNA药物Lepodisiran也在NEJM上发布了二期临床ALPACA试验结果，该试验共入组320例高Lp(a)患者，分别在基线和180天接受安慰剂、两次Lepodisiran 16/96mg、Lepodisiran 400mg和安慰剂各一次、两次Lepodisiran 400mg，在60-180天范围内Lepodisiran的16/96/400mg剂量组的Lp(a)平均降幅分别为40.8%/75.2%/93.9%，在第30-360天范围内上述四个组的Lp(a)平均降幅分别为41.2%/77.2%/88.5%/94.8%；安全性方面，需要注意的是Lepodisiran组的注射反应发生率为8.1%-11.6%、肝酶升高发生率为2.7%-5.8%。https://doi-org.libproxy1.nus.edu.sg/10.1056/NEJMoa2415818除此以外，值得关注的进展还包括：Donanemab在欧洲批准遇阻、主要还是源于对ARIA风险的顾虑，JAK抑制剂Baricitinib公布青少年斑秃的三期临床结果。看了医药武林中GLP-1双雄这么久的激烈争斗，虽然这一代看起来胜负已分，但也有惨胜的苗头，于是LLY在面对竞争问题时动辄就王顾左右把Orfo抬出来说事，特别是在NVO后续管线凋敝的情况下。这种态度，是不是让人联想起大理段氏皇位之争到了最后，段延庆对段正淳的心理优势最终落脚在：“我有儿子呀！”礼来LLY往期季报分析：【医苑观畴】主流技术方向谁说了算：2022年上半年全球大药企核心产品管线进展总览【医苑观畴】主流技术方向谁说了算：2022年下半年全球大药企核心产品管线进展总览【医苑观畴】2023年上半年全球大药企核心进展总览【医苑观畴】2024年一季度海外药企进展更新：礼来LLY【医苑观畴】2024年二季度海外药企进展更新：礼来LLY【医苑观畴】2024年三季度海外药企进展更新：礼来LLY【医苑观畴】2024年全年及四季度海外药企进展更新：礼来LLY

TREMFYA® subcutaneous induction demonstrates significant rates of clinical remission and endoscopic improvement at Week 24 in ulcerative colitis Findings build on recent FDA-approval of both routes of administration for induction therapy with TREMFYA® in Crohn's disease SAN DIEGO, May 5, 2025 /PRNewswire/ -- Johnson & Johnson (NYSE: JNJ) today announced new data from the Phase 3 ASTRO study evaluating TREMFYA® (guselkumab) subcutaneous (SC) induction therapy in adults with moderately to severely active ulcerative colitis (UC). The ASTRO Week 24 data build on the Week 12 SC induction data that showed statistically significant and clinically meaningful improvements compared to placebo across all clinical and endoscopic measures consistent with the U.S. Food and Drug Administration (FDA)-approved intravenous (IV) induction regimen evaluated in this population, in the Phase 3 QUASAR study.1,2 TREMFYA® is the first and only IL-23 inhibitor to demonstrate robust results with a fully SC regimen. These findings are among 24 abstracts highlighting the Company's research being presented at Digestive Disease Week (DDW) 2025. Data at Week 24 show patients treated with TREMFYA® 400 mg SC induction followed by SC maintenance dose regimens of either 100 mg every eight weeks (q8w) or 200 mg every four weeks (q4w) demonstrated statistically significant and clinically meaningful improvements across all clinical and endoscopic measures compared with patients receiving placebo.1 "Data from the ASTRO study demonstrate that subcutaneous induction treatment with TREMFYA provides clinically meaningful remission in patients with ulcerative colitis, similar to the effects seen with intravenous induction," said Millie Long, M.D., MPH, Professor of Gastroenterology and Hepatology at the University of North Carolina at Chapel Hill and study investigator.e "The availability of both subcutaneous and intravenous induction options would offer physicians and patients greater flexibility in their treatment approach." Furthermore, at Week 24, in prespecified analyses of subpopulations defined by prior advanced therapy treatment status, TREMFYA® demonstrated statistically significant results across endpoints in both biologic and JAK inhibitor-naïve and biologic and JAK inhibitor-refractory patients. Safety data from the ASTRO study were consistent with the well-established safety profile of TREMFYA®.1 "These results highlight the potential of TREMFYA to redefine ulcerative colitis care with a fully subcutaneous induction and maintenance regimen that offers a convenient option with meaningful clinical and endoscopic improvements," said Esi Lamousé-Smith, MD, PhD, Vice President, Gastroenterology Disease Area Lead, Immunology, Johnson & Johnson Innovative Medicine. "Our goal is to reshape UC care and empower prescribers with a differentiated and effective treatment that offers the option of patient self-administration from day one." TREMFYA® is the first and only approved, dual-acting monoclonal antibody that blocks IL-23 while also binding to CD64, a receptor on cells that produce IL-23. IL-23 is a cytokine secreted by activated monocyte/macrophages and dendritic cells that is known to be a driver of immune-mediated diseases including UC.3,4,5,6,7 TREMFYA® received FDA approval in September 2024 for the treatment of adult patients with moderately to severely active UC and is currently administered via an IV induction regimen, followed by a SC maintenance regimen. In November 2024, a supplemental Biologics License Application (sBLA) was submitted to the FDA seeking approval of a SC induction regimen of TREMFYA® for the treatment of adults with moderately to severely active UC. TREMFYA® was also approved by the FDA in March 2025 for SC and IV induction options for the treatment of adults with moderately to severely active Crohn's disease (CD). For a full list of all data being presented at DDW visit: Editor's Notes: a. Clinical remission was defined as a Mayo stool frequency subscore of 0 or 1 and not increased from baseline, a Mayo rectal bleeding subscore of 0, and a Mayo endoscopic subscore of 0, or 1 with no friability present on the endoscopy. b. Symptomatic remission per Mayo score is defined as a stool frequency subscore of 0 (normal number of stools) or 1 (1 to 2 stools more than normal) and a rectal bleeding subscore of 0 (no blood seen). c. Endoscopic improvement was defined as an endoscopy subscore of 0 or 1 with no friability present on the endoscopy. d. Clinical response is defined as decrease from baseline in the modified Mayo score by greater than or equal to (>=) 30 percent (%) and >=2 points, with either a >=1-point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1. e. Dr. Long is a paid consultant for Johnson & Johnson. She has not been compensated for any media work. ABOUT THE ASTRO STUDY (NCT05528510) ASTRO is a randomized, double-blind, placebo-controlled, parallel-group, multicenter, treat-through Phase 3 study designed to evaluate the efficacy and safety of TREMFYA® SC induction therapy (400 mg at Weeks 0, 4, and 8) in adults with moderately to severely active ulcerative colitis who had an inadequate response or intolerance to conventional therapy (e.g., thiopurines or corticosteroids), prior biologics (TNF antagonists or vedolizumab) and/or ozanimod or approved JAK inhibitors. Patients (n = 418) were randomized 1:1:1 to receive TREMFYA® 400 mg SC induction at Weeks 0, 4 and 8 followed by TREMFYA® 200 mg SC every 4 weeks (q4w); or TREMFYA® 400 mg SC induction at Weeks 0, 4 and 8, followed by TREMFYA® 100 mg SC every 8 weeks (q8w); or placebo. The maintenance dose regimens in ASTRO (200 mg SC q4w and 100 mg SC q8w) are the same as those evaluated in the Phase 3 QUASAR program which established the efficacy and safety profile of IV induction followed by SC maintenance therapy in patients with moderate to severely active UC.8 ABOUT ULCERATIVE COLITIS Ulcerative colitis (UC) is a chronic disease of the large intestine, also known as the colon, in which the lining of the colon becomes inflamed and develops tiny open sores, or ulcers, that produce pus and mucus. It is the result of the immune system's overactive response. Symptoms vary but may typically include loose and more urgent bowel movements, rectal bleeding or bloody stool, persistent diarrhea, abdominal pain, loss of appetite, weight loss, and fatigue.9 ABOUT TREMFYA® (guselkumab) Developed by Johnson & Johnson, TREMFYA® is the first approved fully-human, dual-acting monoclonal antibody designed to neutralize inflammation at the cellular source by blocking IL-23 and binding to CD64 (a receptor on cells that produce IL-23). Findings for dual-acting are limited to in vitro studies that demonstrate guselkumab binds to CD64, which is expressed on the surface of IL-23 producing cells in an inflammatory monocyte model. The clinical significance of this finding is not known. TREMFYA® is a prescription medicine approved in the U.S. to treat: adults with moderate to severe plaque psoriasis who may benefit from taking injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet or UV light). adults with active psoriatic arthritis. adults with moderately to severely active ulcerative colitis. adults with moderately to severely active Crohn's disease.5 TREMFYA® is approved in Europe, Canada, Japan, and a number of other countries for the treatment of adults with moderate-to-severe plaque psoriasis and for the treatment of adults with active psoriatic arthritis. In addition, TREMFYA ® is approved in Europe, Japan and Brazil for the treatment of adult patients with moderately to severely active UC and in Brazil and China for the treatment of adults with moderately to severely active CD. Johnson & Johnson maintains exclusive worldwide marketing rights to TREMFYA®. For more information, visit: . IMPORTANT SAFETY INFORMATION What is the most important information I should know about TREMFYA®? TREMFYA® is a prescription medicine that may cause serious side effects, including: Serious Allergic Reactions. Stop using TREMFYA® and get emergency medical help right away if you develop any of the following symptoms of a serious allergic reaction: Infections. TREMFYA® may lower the ability of your immune system to fight infections and may increase your risk of infections. Your healthcare provider should check you for infections and tuberculosis (TB) before starting treatment with TREMFYA® and may treat you for TB before you begin treatment with TREMFYA® if you have a history of TB or have active TB. Your healthcare provider should watch you closely for signs and symptoms of TB during and after treatment with TREMFYA®. Tell your healthcare provider right away if you have an infection or have symptoms of an infection, including: Liver problems. With the treatment of Crohn's disease or ulcerative colitis, your healthcare provider will do blood tests to check your liver before and during treatment with TREMFYA®. Your healthcare provider may stop treatment with TREMFYA® if you develop liver problems. Tell your healthcare provider right away if you notice any of the following symptoms: Do not use TREMFYA® if you have had a serious allergic reaction to guselkumab or any of the ingredients in TREMFYA®. Before using TREMFYA®, tell your healthcare provider about all of your medical conditions, including if you: have any of the conditions or symptoms listed in the section "What is the most important information I should know about TREMFYA®?" have an infection that does not go away or that keeps coming back. have TB or have been in close contact with someone with TB. have recently received or are scheduled to receive an immunization (vaccine). You should avoid receiving live vaccines during treatment with TREMFYA®. are pregnant or plan to become pregnant. It is not known if TREMFYA® can harm your unborn baby. Pregnancy Registry: If you become pregnant during treatment with TREMFYA®, talk to your healthcare provider about registering in the pregnancy exposure registry for TREMFYA®. You can enroll by visiting , by calling 1-877-311-8972, or emailing [email protected]. The purpose of this registry is to collect information about the safety of TREMFYA® during pregnancy. are breastfeeding or plan to breastfeed. It is not known if TREMFYA® passes into your breast milk. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. What are the possible side effects of TREMFYA®? TREMFYA® may cause serious side effects. See "What is the most important information I should know about TREMFYA®?" The most common side effects of TREMFYA® include: respiratory tract infections, headache, injection site reactions, joint pain (arthralgia), diarrhea, stomach flu (gastroenteritis), fungal skin infections, herpes simplex infections, stomach pain, and bronchitis. These are not all the possible side effects of TREMFYA®. Call your doctor for medical advice about side effects. Use TREMFYA® exactly as your healthcare provider tells you to use it. Please read the full Prescribing Information, including Medication Guide, for TREMFYA® and discuss any questions that you have with your doctor. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit , or call 1-800-FDA-1088. Dosage Forms and Strengths: TREMFYA® is available as 100 mg/mL and 200 mg/2mL for subcutaneous injection and as a 200 mg/20 mL (10 mg/mL) single dose vial for intravenous infusion. ABOUT JOHNSON & JOHNSON At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity.   Learn more at or at Follow us at @JNJInnovMed. Janssen Research & Development, LLC and Janssen Biotech, Inc. are Johnson & Johnson companies.  Cautions Concerning Forward-Looking Statements This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding TREMFYA®. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's most recent Annual Report on Form 10-K, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at , or on request from Johnson & Johnson. Johnson & Johnson does not undertake to update any forward-looking statement as a result of new information or future events or developments. References: 1 Peyrin-Biroulet, et al. Efficacy and safety of subcutaneous guselkumab induction therapy in patients with Ulcerative Colitis: Results through week 12 from the phase 3 ASTRO study. Results from the Phase 3 ASTRO study. Oral presentation (#OP10) at the 20th Congress of the European Crohn's and Colitis Organization (ECCO). February 2025. 2 Long M, et al. Efficacy And Safety Of Subcutaneous Guselkumab Induction Therapy In Patients With Ulcerative Colitis: Results Through Week 24 From The Phase 3 Astro Study. Oral presentation (#4241895) at Digestive Disease Week 2025. May 2025. 3 Atreya R, Abreu MT, Krueger JG, et al. Guselkumab, an IL-23p19 subunit-specific monoclonal antibody, binds CD64+ myeloid cells and potentially neutralizes IL-23 produced from the same cells. Poster presented at: 18th Congress of the European Crohn's and Colitis Organization (ECCO); March 1-4, 2023; Copenhagen, Denmark. Poster P504. 4 Kreuger JG, Eyerich K, Kuchroo VK. Il-23 past, present, and future: a roadmap to advancing IL-23 science and therapy. Front Immunol. 2024; 15:1331217. doi:10.3389/fimmu.2024.1331217. 5 TREMFYA® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc. 6 Skyrizi® [Prescribing Information]. North Chicago, IL: AbbVie, Inc. 7 Omvoh™ [Prescribing Information]. Indianapolis, IN: Eli Lilly and Company. 8 National Institutes of Health: Clinicaltrials.gov. A Study of Guselkumab Therapy in Participants With Moderately to Severely Active Ulcerative Colitis (ASTRO). Identifier: NCT05528510. . Accessed March 2025. 9 Crohn's & Colitis Foundation. What is ulcerative colitis? Available at: . Accessed March 2025 SOURCE Johnson & Johnson WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED