Varenicline Tartrate

中美地缘政治高度不确定性的扰动背景下，远大医药近6个交易日累计上涨近40%，无惧行业波动。值得注意的是，国际大行中金在5月13日上调目标价20.0%至9.6港币，这是中金年内第三次上调远大医药的目标价。大涨背后是远大医药密集的创新进展等积极消息的释放，包括：脓毒症创新药STC3141的二期临床成功、创新核素偶联药物TLX591加入国际多中心三期申请获受理、诊断RDC产品TLX591-CDx完成三期患者全部入组并计划在年内递交上市、肝癌创新精准诊断RDC产品GPN02006临床结果将亮相SNMMI大会，以及公司成都温江核药基地计划今年投入运营等等，这充分印证了公司厚积薄发的科技创新战略正在逐渐兑现，2025年公司创新药布局爆发正当时。随着公司更多的创新药布局一一开花结果，公司的投资与成长逻辑已全面蜕变，凸显港股创新药龙头气势。01核药爆发：批量颠覆性大品种蓄势待发核药板块，是远大医药创新药布局的最强尖兵之一。公司首个商业化核药品种为易甘泰®（钇[90Y]微球注射液），为全球唯一获批用于结直肠癌肝转移选择性内放射治疗（SIRT）的产品，2022-2024年分别实现销售额超过6000万港元、2亿港元和4.9亿港元，呈现了高速放量增长。易甘泰®的增长潜力还远远未被释放，其未来不仅有望惠及国内每年36万新发的肝癌患者，并且有望进一步探索后线治疗的潜力（如肝癌术后辅助治疗、联合靶向治疗等）。易甘泰®只是“商业化先锋”，远大医药核药板块处于一个全面爆发的关键窗口，要探析公司的强劲布局，诺华便是一个很好的对标或参照例子。2024年诺华核药两大商业化核心产品Pluvicto、Lutathera分别实现13.92亿美元（yoy+42%）、7.24亿美元（yoy+20%），整体板块收入超过20亿美元，而Jefferies更是给出了Pluvicto销售峰值将超过50亿美金的预测，另外Lutathera在2024年扩大适应症纳入了12岁及以上SSTR+胃肠胰神经内分泌肿瘤儿童患者，也即将步入10亿美元分子行列。‌显然，无论是Pluvicto还是Lutathera都分别在前列腺癌、神经内分泌适应症中展现了强大市场扩张力，这一势头未有减弱迹象并且有着加速迹象。远大医药，目前在Pluvicto、Lutathera对应的PSMA靶点、SSTR靶点核药RDC上分别布局了对应的me-better管线TLX591和ITM-11，如今正在奔向关键临床里程碑。TLX591是一款基于J591单抗的RDC药物，其通过抗体靶向PSMA，搭载治疗性放射性核素177Lu，精准输送至肿瘤部位。相比诺华Pluvicto，TLX591在多个方面具备潜在me better的特质：1）更精准的靶向治疗： TLX591通过抗体特异性除了更精准外，药物在PSMA阳性肿瘤的穿透性和滞留时间更长，有望达到更好的疗效；2）给药依从性：相比市面上长达六周期、持续30周的放射性配体治疗方案，TLX591仅需间隔14天的双剂给药（总周期约1个月），大幅缩短治疗周期；3）安全性：TLX591通过肝脏代谢清除，有效避免了肾脏毒性，而且其大分子结构使其对唾液腺和泪腺的摄取率极低，减少口干症和干眼症等常见不良反应发生率，改善患者生活质量。核药诊疗一体化的组合可以进一步发挥产品的效能。基于PSMA成像的优越性，TLX591-CDx是欧美最受医患青睐的诊断性核药，其基于放射性核素-小分子偶联技术的靶向PSMA（在90%以上的原发性和转移性前列腺癌细胞表面过表达），可用于检测基于血清PSA水平升高的复发前列腺癌患者。2024年TLX591-CDx实现近5.17亿美元的销售额，并于2025Q1取得近1.51亿美元的销售额，同比增长近35%。目前Pluvicto尚未在国内上市，随着TLX591-CDx预计在年内递交NDA，远大医药TLX591-CDx将有望在Pluvicto上市后搭乘其放量的东风；同时，待未来TLX591顺利加入国际多中心三期临床，其与TLX591-CDx有望为国内前列腺疾病患者带来更精准、高效的诊疗方案，并为远大医药实现前列腺癌的“诊疗一体化”。ITM-11是一款无载体177Lu与生长抑素类似物结合的RDC，其同样是一款潜在me better产品。其具体优势包括：1）ITM-11采用无载体技术，更高的比活度和纯度，生产杂质少，可提升肿瘤靶向效率；2）ITM-11半衰期更长，其采用每8周一次间隔给药，具备更高的患者依从性；3）ITM-11的潜在安全性更高，在过往临床中未观察到严重不良事件（SAE）。药物有效性来看，ITM-11的全球三期临床COMPOSE研究显示：在侵袭性2/3级SSTR阳性的胃肠或胰腺来源的神经内分泌肿瘤GEP-NETs患者中，患者的mPFS高达34.5个月，且未观察到严重的不良事件。与Lutathera非头对头数据比较下，ITM-11有望在整体的疗效（mPFS显著提升，Lutathera一线治疗在22个月左右）、安全性上成为同类最佳产品。目前诺华Lutathera并未在国内上市，远大医药ITM-11国内三期临床在今年三月已经实现首例患者入组，其有望成为国内首个商业化靶向SSTR的RDC产品，享受市场独占期。多款创新核药的管线为远大医药未来增长赋予了稳健的确定性，同时核药的商业化供应背后必须有着强大的产业链保障，经过多年深耕，远大医药在核药领域已实现了研发、生产、销售、监管资质等多个环节的全方位布局，建立了完整的产业链。同时，远大医药预计投入30亿的成都温江放射性药物全球研发及生产基地，将于今年投入运营，有望加速创新核药管线的落地，并进一步公司核药领域的领先地位。该基地是全球首个零辐射智能核药工厂，是目前国际范围内核素种类最全、自动化程度最高的智能工厂，未来将巩固远大医药全球核药研发中心网络的布局，其预计将于今年年底至2026年陆续实现产品的FDA临床申报。值得一提的是，今天远大医药还公布了其用于治疗肝细胞癌（HCC）的创新RDC产品GPN02006将于2025年SNMMI（核医学与分子影像学会）年会公布重磅临床结果。GPN02006是一款基于放射性核素-抗体偶联技术的靶向磷脂酰肌醇蛋白聚糖3 (GPC-3)的诊断型放射性药物。该产品早前临床研究数据展现了卓越的安全性和显像效能：所有受试者给药后均未报告任何药物相关不良反应，安全耐受性表现优异；给药后30分钟即可实现高质量显像，充分满足肝细胞癌临床快速诊断需求。本次其亮相SNMMI，不仅体现了GPN02006的潜力——有望成为全球首个针对GPC-3靶点的HCC诊断类RDC产品，同时也标志着远大医药核药产业全球化发展迈入新的阶段。02STC3141：全球脓毒症创新药FIC远大医药自研创新药STC3141脓毒症临床结果一鸣惊人，让市场重新审视公司的创新实力。脓毒症是全球市场公认最难攻克的适应症之一，由于发病机制复杂且病理过程涉及感染、免疫反应、代谢紊乱等多重机制，难以通过单一靶点药物全面干预，这也让远大医药的STC3141价值凸显。脓毒症领域缺乏有效治疗药物，目前抗生素类、免疫调节剂等传统药物为主，21世纪以来仅有重组活化蛋白C获批治疗脓毒症（后因疗效不确切撤市）。但由于脓毒症是美国住院患者的第一大死因（死亡率高达35% ~54%），并且中国每年约有近250万脓毒症患者，市场空间广阔；据Wise Guy Reports数据，2024年全球脓毒症治疗药物市场规模为125.4亿美元，预计到2032年市场规模将达到193.7亿美元，年均复合增长率为5.58%。远大医药STC3141的治疗机制围绕脓毒症治疗的核心目标——维持免疫稳态，其活性成分是一种多阴离子分子，研究表明脓毒症患者体内循环组蛋白水平升高与疾病严重程度相关，STC3141能够通过中和细胞外游离组蛋白和中性粒细胞陷阱网（NETs），减少炎症反应和组织损伤。STC3141国内治疗脓毒症二期临床结果显示，高剂量治疗组在主要终点第7天序贯器官衰竭评估（SOFA）评分较基线变化的表现显著优于安慰剂组，同时次要终点趋势与主要终点一致，患者安全性、耐受性良好。尽管未披露具体数据，但从“显著优于安慰剂组”的口径在脓毒症这样危重症适应症来说显然是大获成功。另外，STC3141的疗效和安全性也可以在过往的早期临床中初见端倪，STC3141在多个临床中帮助患者脱离呼吸机、脱离升压药和缩短ICU住院时间等有效性指标方面均体现了积极信号。值得注意的是，2024年底NIH公示的STC3141一期临床研究，在26名SOFA评分≥2的脓毒症患者中，大部分患者安全性、耐受性良好，有18名（69.2%）完成了ICU第8天的完整治疗方案，其余8名患者有4名提前出院、1名过早出ICU、1名SAE、1名需要其他治疗和1名死亡，这彰显了STC3141在患者中的安全性与耐受性。STC3141在国内二期临床明确了初步成药性的背景下，成为全球脓毒症潜在First in class药物候选毋庸置疑，若未来远大医药顺利申请STC3141突破性治疗药物资格，该产品的开发也有望进一步提速，并早日惠及广大脓毒症患者。而更大的悬念，在于STC3141对外授权的价值判断。由于脓毒症验证性创新临床管线稀缺，并且欧美住院患者用药花费不菲，巨额BD是可以预期的。从过往可参考的案例看，脓毒症药物开发商AM-Pharma的重组人碱性磷酸酶ilofotase alfa在脓毒症相关急性肾损伤适应症曾经未达到二期临床终点的背景下，仍基于对肾功能显著、渐进和持续改善潜力被协和麒麟看中，后2021年协和麒麟以2000万欧元首付+3000万欧元及1.95亿欧元监管里程碑费用买下日本开发权益。远大医药STC3141作为疗效、安全性已被验证并且拥有部分海外人群临床数据的FIC药物，拿下总额巨大的BD，想必市场不会感到意外。除了STC3141之外，远大医药还布局了一款脓毒症新药APAD，通过拮抗多种病原体相关分子（PAMPs），抑制免疫细胞过度活化，阻断脓毒症早期炎症风暴的启动，据介绍APAD与STC3141存在协同作用。03逻辑体系转变随着多年创新药的布局在2025年开始爆发，远大医药显然形成一套全新成长性逻辑。首先是各个创新药板块未来两年有一大批产品将迎来商业化放量，这些产品的体量将至少“再造一个”远大医药：（图源：远大医药2024年年报）1）核药领域除了易甘泰®（预计未来国内销售峰值有望超过50亿人民币）之外，公司诊断性核药TLX591-CDx国内三期临床完成全部患者入组并将于年内递交国内NDA申请、肾透明细胞癌诊断产品TLX250-CDx国内III期已完成首例入组、治疗性核药ITM-11国际多中心III期临床国内完成首例入组，以及治疗性核药TLX591加入国际多中心III期临床获受理，未来这些后期产品预计至少能贡献30亿人民币的收入（核心为治疗性核药），这还没有考虑后续其他早期管线。2）眼药方面，目前公司干眼症FIC产品酒石酸伐尼克兰鼻喷雾剂OC-01已经商业化，鉴于目前干眼症常规药物人工泪液玻璃酸钠滴眼液等药物在2023年均突破10亿规模，OC-01未来市场潜力亦值得期待；同时公司两款治疗蠕形螨睑缘炎滴眼液GPN01768和白内障术后抗炎滴眼液GPN00833均处于商业化冲刺阶段，两者销售峰值均有望冲刺10亿人民币的规模。3）吸入制剂方面公司拥有国内针对过敏性鼻炎的轻、中、重症全方位布局，目前包括已上市的布地奈德鼻喷雾剂及丙酸氟替卡松鼻喷剂、冲击商业化阶段的糠酸莫米松鼻喷雾剂，以及处于新药上市审核阶段的Ryaltris创新复方鼻喷剂，尽管前三款是仿制药，但具备良好的竞争格局和一定剂型壁垒，能够贡献可观的现金流，另外Ryaltris作为起效迅速并能治疗季节性过敏性鼻炎（SAR）的创新药物，重磅产品潜质凸显，保守预计公司吸入制剂产品组合未来至少可贡献25-30亿人民币收入。仅统计上述三大创新板块，未来就有望为远大贡献超过130亿人民币的营收，考虑到创新药的净利率高于传统品种，保守以20%净利率测算，将创造近30亿人民币的净利润，相当于再造一个远大医药。这只是远大医药向全球展示其真正内核实力的开始，如今随着脓毒症FIC管线STC3141验证性临床的开花结果，以及创新眼药、核药板块管线的产学研转化和自主开发，迅速打开了市场对公司在海外市场发展的想象空间，其中最大的预期要属STC3141海外授权的推进。再从估值重估的角度而言，公司作为股息率高达5-6%的业绩稳健增长的医药龙头，目前远大医药从估值体系并未反应或计价上述两大逻辑的价值，或许如今的起点，仅仅只是一个市场价值发现的起点。结语：远大医药2025年创新药里程碑的密集井喷，不仅得益于公司过去多年的前瞻性创新布局，还得益于公司坚定转型创新的卓越执行力，以及打造国际化差异竞争力的不懈坚持。如今远大医药在核药、呼吸及危重症和眼药领域等前沿板块的持续创新兑现，恰恰是公司厚积薄发的正向反馈，而股价的不断新高，是市场给予公司坚定创新最直白的肯定。远大医药的价值发现之路，才刚刚启程。识别微信二维码，添加抗体圈小编，符合条件者即可加入抗体圈微信群！请注明：姓名+研究方向！本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

ORCA-3 Demonstrated a Significant Increase in Quitting and Reduction in Nicotine Cravings for Cytisinicline-Treated Participants Compared to Placebo Cytisinicline New Drug Application (NDA) Submission to FDA Planned for June 2025 SEATTLE and VANCOUVER, British Columbia, April 21, 2025 (GLOBE NEWSWIRE) -- Achieve Life Sciences, Inc. (Nasdaq: ACHV), a late-stage specialty pharmaceutical company focused on the global development and commercialization of cytisinicline as a treatment of nicotine dependence for smoking cessation, today announced that complete trial results from its ORCA-3 were published in the Journal of the American Medical Association (JAMA) Internal Medicine. ORCA-3 was the second randomized, placebo-controlled Phase 3 clinical trial evaluating cytisinicline for smoking cessation in 792 U.S. adults. The authors concluded that ORCA-3 reaffirms cytisinicline’s efficacy and tolerability for smoking cessation in adult smokers at both 6- and 12-week treatment durations, including reduction in nicotine cravings and extended cessation benefits through 24 weeks. In addition to previously reported topline results announced in May 2023, the published completed trial results provided further evidence of cytisinicline’s highly targeted effect on treating nicotine dependence by binding to specific nicotine receptors. These consistent results, now published from two large, randomized Phase 3 trials, demonstrated that cytisinicline significantly reduced nicotine cravings and increased the likelihood of quitting smoking. In clinical trials, cytisinicline was well tolerated, which is thought to be due to limited other off-target binding effects that can result in side effects known to be associated with currently available treatments. Similar to the first Phase 3 trial, ORCA-3 participants had an average age of 53 years, smoked a median of 20 cigarettes per day at baseline, and had a median smoking history of 36 years with four prior quit attempts. “Most people who smoke want to quit and it often takes multiple attempts to do so successfully. Our trial participants were no exception and had multiple previous quit attempts, although less than half had previously tried varenicline, possibly due to its well-known adverse event profile,” said Cindy Jacobs, MD, PhD, President and Chief Medical Officer of Achieve Life Sciences. “Cytisinicline is very selective in targeting only nicotine receptors and has shown limited binding to other off-target receptors that can cause side effects, like nausea and gastrointestinal disturbances. We believe this leads to a highly tolerable treatment with cytisinicline, as demonstrated in our clinical trial program.” Results from the ORCA-3 study show that cytisinicline significantly increased the odds of smoking cessation compared to placebo. Cytisinicline also reduced nicotine craving which led to decreased nicotine intake, even among those who continued smoking, as evidenced by both lower craving scores and reduced cotinine levels, a well-known metabolite of nicotine. “More deaths each year in the U.S. are attributed to cigarette smoking than to any other preventable cause, and our current smoking cessation treatment options are limited,” said Nancy Rigotti, MD, Professor of Medicine at Harvard Medical School, Director of Tobacco Research and Treatment Center, Massachusetts General Hospital, and ORCA Program Investigator. “The study findings published today suggest that cytisinicline, if approved by the FDA, could help many smokers to quit and reduce the smoking-related risks to their health.” Achieve plans to submit the cytisinicline New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in June 2025. About ORCA-3 The Phase 3 ORCA-3 trial evaluated 792 adults who smoked cigarettes daily and was conducted at 20 clinical trial locations in the U.S. The trial was initiated in January 2022 and completed enrollment in September 2022, with topline results reported in May 2023. ORCA-3 participants received 3mg cytisinicline dosed 3 times daily for either 6 or 12 weeks and were monitored through 24 weeks post randomization. The trial was blinded, placebo-controlled, and all subjects received behavioral support for the duration of the trial. The primary endpoint was biochemically verified continuous abstinence during the last four weeks of treatment. Secondary outcome measures assessed continued abstinence rates through 6 months from the start of study treatment. The full manuscript is published in Journal of the American Medical Association (JAMA) Internal Medicine. About Achieve Life Sciences, Inc. Achieve Life Sciences is a late-stage specialty pharmaceutical company committed to addressing the global smoking health and nicotine dependence epidemic through the development and commercialization of cytisinicline. The company has successfully completed two Phase 3 studies with cytisinicline for smoking cessation and one Phase 2 study with cytisinicline in vaping cessation. The company has fully enrolled its ongoing open-label safety study with cytisinicline and plans to submit its new drug application for smoking cessation in June 2025. Achieve has also conducted a successful end-of-Phase 2 meeting with the FDA for a future vaping indication. About Cytisinicline There are approximately 29 million adults who smoke combustible cigarettes.1 Tobacco use is currently the leading cause of preventable death that is responsible for more than eight million deaths worldwide and nearly half a million deaths in the United States annually.2,3 More than 87% of lung cancer deaths, 61% of all pulmonary disease deaths, and 32% of all deaths from coronary heart disease are attributable to smoking and exposure to secondhand smoke.3 In addition, there are over 11 million adults in the United States who use e-cigarettes, also known as vaping.4 In 2024, approximately 1.6 million middle and high school students in the United States reported using e-cigarettes.5 There are no FDA-approved treatments indicated specifically as an aid to nicotine e-cigarette cessation. Cytisinicline has been granted Breakthrough Therapy designation by the FDA to address this critical need. Cytisinicline is a plant-based alkaloid with a high binding affinity to the nicotinic acetylcholine receptor. It is believed to aid in treating nicotine addiction for smoking and e-cigarette cessation by interacting with nicotine receptors in the brain, reducing the severity of nicotine craving symptoms, and reducing the reward and satisfaction associated with nicotine products. Cytisinicline is an investigational product candidate being developed for the treatment of nicotine addiction and has not been approved by the Food and Drug Administration for any indication in the United States. Forward Looking Statements This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding the timing and nature of cytisinicline clinical development and regulatory review and approval, data results and commercialization activities, the potential market size for cytisinicline, the potential benefits, efficacy, safety and tolerability of cytisinicline, the development and effectiveness of new treatments, and the successful commercialization of cytisinicline. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. Achieve may not actually achieve its plans or product development goals in a timely manner, if at all, or otherwise carry out its intentions or meet its expectations or projections disclosed in these forward-looking statements. These statements are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and assumptions that could cause actual results to differ materially from those described in the forward-looking statements, including, among others, the risk that cytisinicline may not demonstrate the hypothesized or expected benefits; the risk that Achieve may not be able to obtain additional financing to fund the development and commercialization of cytisinicline; the risk that cytisinicline will not receive regulatory approval in a timely manner or at all, or be successfully commercialized; the risk that new developments in the smoking and vaping cessation landscapes require changes in business strategy or clinical development plans; the risk that Achieve’s intellectual property may not be adequately protected; general business and economic conditions; risks related to the impact on our business of macroeconomic and geopolitical conditions, including fluctuating inflation, interest and tariff rates, volatility in the debt and equity markets, actual or perceived instability in the global banking system, global health crises and pandemics and geopolitical conflict and the other factors described in the risk factors set forth in Achieve’s filings with the Securities and Exchange Commission from time to time, including Achieve’s Annual Reports on Form 10-K and Quarterly Reports on Form 10-Q. Achieve undertakes no obligation to update the forward-looking statements contained herein or to reflect events or circumstances occurring after the date hereof, other than as may be required by applicable. Achieve Contact Nicole Jones ir@achievelifesciences.com 425-686-1510 References 1VanFrank B, Malarcher A, Cornelius ME, Schecter A, Jamal A, Tynan M. Adult Smoking Cessation — United States, 2022. MMWR Morb Mortal Wkly Rep 2024;73:633–641. 2World Health Organization. WHO Report on the Global Tobacco Epidemic, 2019. Geneva: World Health Organization, 2017. 3U.S. Department of Health and Human Services. The Health Consequences of Smoking – 50 Years of Progress. A Report of the Surgeon General, 2014. 4Cornelius ME, Loretan CG, Jamal A, et al. Tobacco Product Use Among Adults – United States, 2021. MMWR Morb Mortal Wkly Rep 2023;72:475–483. 5Jamal A, Park-Lee E, Birdsey J, et al. Tobacco Product Use Among Middle and High School Students — National Youth Tobacco Survey, United States, 2024. MMWR Morb Mortal Wkly Rep 2024;73:917–924. Released April 21, 2025