Radium Ra-223 Dichloride

用于治疗转甲状腺素蛋白淀粉样变性心肌病的心脏病药物Beyonttra®（acoramidis）已在欧洲成功获批非激素类创新药elinzanetant用于治疗与更年期相关的中重度血管舒缩症状（VMS，也称为潮热）， 预计2025年在美国和欧洲上市达罗他胺在前列腺癌治疗领域的第三个适应症，以及非奈利酮的第二个适应症——用于治疗一种常见心力衰竭（心衰）——预计在2025年下半年上市凭借在眼科领域的领导地位，潜在重磅药物EyleaTM 8mg（阿柏西普8mg）在第三个适应症的III期临床试验中取得积极结果，很快将向欧盟提交上市许可申请在帕金森病治疗领域推进细胞疗法和基因疗法的旗舰项目启动并推进心血管/肾脏和肿瘤等重点治疗领域的多个创新和差异化项目的临床开发近日，在拜耳处方药2025年全球媒体日之际，公司展示了其处方药事业部的增长战略和研发管线的重大进展。公司正在扩展其心脏病学产品组合，推出Beyonttra®，用于治疗转甲状腺素蛋白淀粉样变性心肌病 （ATTR-CM），并计划在年底前推出非奈利酮（可申达®），用于治疗常见心衰，即左心室射血分数 （LVEF）≥40%的心衰。同时，elinzanetant作为治疗更年期女性中重度血管舒缩症状的非激素类疗法，预计将在2025年夏末首次上市。在肿瘤领域，公司增长动力达罗他胺（诺倍戈®）的第三个适应症预计将在2025年获得在美国的批准，允许达罗他胺与雄激素剥夺疗法（ADT）联合使用，治疗转移性激素敏感性前列腺癌（mHSPC）成年患者。“2025年是拜耳处方药具有里程碑意义的上市年，公司正在全力以赴推动研发管线进展，”拜耳集团管理委员会成员、拜耳处方药事业部全球总裁Stefan Oelrich表示。“我们的增长战略进展顺利，并产生了巨大价值。今年，我们将向市场推出多款具有重磅药物潜力的突破性产品。”具有重磅药物潜力的6款产品向上滑动阅览诺倍戈®（达罗他胺）拜耳计划于2025年推出诺倍戈®的第三个适应症，ARANOTE试验的有力数据为其提供了支持，该试验研究了达罗他胺联合ADT相较于安慰剂联合ADT治疗mHSPC患者的有效性和安全性。诺倍戈®已获批联合ADT和多西他赛治疗mHSPC。此外，它还获批联合ADT治疗具有高危转移风险的非转移性去势抵抗性前列腺癌（nmCRPC）成年患者。可申达®（非奈利酮）在FINEARTS-HF III期临床研究中，非奈利酮在心衰患者（LVEF ≥40%）中显示出心血管结果的统计学显著改善。基于此积极数据，拜耳已在美国、欧盟、中国和日本提交了该适应症的上市申请。非奈利酮是唯一一款在III期研究中证明对LVEF≥40%的心衰患者具有心血管获益的盐皮质激素受体（MR）通路的靶向药物。非奈利酮已获批用于治疗与2型糖尿病相关的慢性肾脏病（CKD）成人患者。Beyonttra® (acoramidis)今年2月，欧盟委员会批准了acoramidis（商品名为Beyonttra®）的上市许可，用于治疗野生型或变异型转甲状腺素淀粉样变性的患有心肌病的成年患者（ATTR-CM）。ATTR-CM是一种进行性致死性疾病，通过浸润性、局限性心肌病导致心衰。由于心脏内持续存在淀粉样物质沉积，患者面临疾病持续进展的风险。Beyonttra®是一种高选择性小分子、口服给药的、接近完全（≥90%）的转甲状腺素蛋白（TTR）稳定剂。该药物已在欧洲成功上市，德国是首个上市国家。Elinzanetant在三项III期临床试验（OASIS-1、2、3）中，elinzanetant已成功证明其在减少与更年期相关的中重度血管舒缩症状（VMS，也称为潮热）的有效性和安全性。今年1月，III期OASIS 4临床取得了积极成果，达成其主要终点，证明了elinzanetant在治疗接受乳腺癌辅助内分泌治疗或患乳腺癌风险较高的女性中重度VMS方面的有效性。在所有四个III期临床试验中，参与者的睡眠障碍和与更年期相关的生活质量方面也有所改善。Elinzanetant正在全球多个市场申请上市许可，拜耳预计其今年将在美国和欧洲获批。EyleaTM 8mg（阿柏西普8mg）在眼科治疗领域，EyleaTM 8mg以其更长的治疗间隔，将有望成为其已获批适应症——新生血管（湿性）年龄相关性黄斑变性（nAMD）和糖尿病性黄斑水肿（DME）——新的标准治疗。2024年12月，全球III期QUASAR研究表明，对于视网膜静脉阻塞（RVO），包括中央、分支和半侧视网膜静脉阻塞，继发黄斑水肿的患者，与当前的标准治疗（艾力雅®2mg每月）给药相比，阿柏西普8mg可以实现给药频率更低的同时，在视力改善方面也具有非劣疗效。详细结果将提交给全球多个卫生监管机构。AsundexianAsundexian是一种选择性口服FXIa抑制剂，作为一种潜在的新型抗血栓疗法，目前正在研究用于预防接受标准抗血小板治疗的患者的缺血性卒中复发。FXIa抑制的机制假设是将卒中预防与出血风险解耦。OCEANIC-STROKE III期临床研究进展顺利，研究了接受标准抗血小板治疗的患者在非心源性缺血性卒中或高危短暂性脑缺血发作后的卒中预防。该研究将于今年晚些时候完成。该适应症此前曾获得美国食品药品监督管理局（FDA）的快速通道资格。影像诊断业务的新对比剂拜耳影像诊断业务提供全面的对比剂产品组合，并显著推进了其磁共振（MRI）的创新研发管线。III期临床研究QUANTI探索了含钆的MRI对比剂gadoquatrane在儿科和成人患者中的广泛潜在适应症，成功达到了主要和全部关键次要终点。与按0.1 mmol Gd/kg体重给药的对照组相比，gadoquatrane的钆剂量减少了60%。减少钆剂量对于需要重复进行对比增强MRI检查的患者以及儿科等弱势患者尤为重要。拜耳计划向全球多个卫生监管机构提交上市申请。帕金森病细胞疗法和基因疗法居领导地位拜耳细胞和基因疗法平台取得了关键进展，达成了重要的临床试验里程碑，特别是在帕金森病领域。Bemdaneprocel是一种在研细胞疗法，通过手术将生成多巴胺的神经细胞前体植入大脑。根据I期临床试验exPDite的积极数据，它将直接推进至帕金森病的III期临床。美国食品药品监督管理局（FDA）已授予bemdaneprocel再生医学先进疗法认定（RMAT），认可其在治疗帕金森病方面的创新潜力。AB-1005是一种治疗帕金森病的在研基因疗法，目前正处于II期临床阶段。REGENERATE-PD临床试验已迎来随机化分组受试者。AB-1005基于腺相关病毒（AAV），将人胶质细胞源性神经营养因子（GDNF）转基因输送到大脑，有可能恢复产生多巴胺的神经元的功能。根据初步临床证据，美国FDA 授予 AB-1005 RMAT 资格，因为它具有减缓中度帕金森病患者病情进展和改善运动结果的潜力。此外，英国药品与保健品监管局（MHRA）授予AB-1005创新通行证认定。来自美国和英国的两项认定突显了AB-1005在帕金森病领域满足全球重大未满足医疗需求的潜力。作为转型的一部分，拜耳聚焦重点研发领域，为肿瘤、心血管疾病和肾脏病、神经学和罕见病、免疫学领域的长期增长建立了高度差异化的研发管线。通过严格的评估和优先排序，拜耳处方药目前完全专注于具有最大未满足需求和最高价值潜力的领域。推进精准肿瘤研发在精准肿瘤治疗领域，口服小分子酪氨酸激酶抑制剂（在研药物BAY 2927088）是针对携带HER2激活突变的非小细胞肺癌（NSCLC）患者的潜在新靶向治疗。在正在进行的评估其安全性和有效性的SOHO-01 I/II期临床研究中，该药物作为二线治疗显示出积极的结果，其潜力得到了美国FDA和中国国家药品监督管理局药品评价中心（CDE）的突破性疗法认定。此外，BAY 2927088还在SOHO-02 III期临床试验中评估作为一线治疗的潜力，针对肿瘤具有HER2激活突变的晚期NSCLC患者。针对携带HER2激活突变的转移性或不可切除实体瘤的成人患者，BAY 2927088的有效性和安全性也在全球panSOHO II期临床试验中进行了研究。最近，在晚期KRAS突变肿瘤患者中还启动了一项I期临床试验，研究药物为BAY 3498264，是一种口服选择性SOS1抑制剂。靶向放射性核素治疗（TRT）是拜耳精准肿瘤药物开发的战略重点领域。多菲戈®是首个也是唯一针对转移性去势抵抗前列腺癌症患者的靶向α治疗方案。基于多菲戈®十余年真实世界经验，拜耳不断发展的TRT产品组合包括新的靶向方法，将α放射性核素（如锕-225）与不同的靶向部分（包括抗体、小分子或肽基分子）结合起来。作为靶向PSMA（前列腺特异性膜抗原）的候选药物，225Ac-pelgifatamab（BAY 3546828）和225Ac-PSMA-Trillium（BAY 3563254）目前正在晚期转移性去势耐受性前列腺癌症（mCRPC）患者中进行I期临床试验。近年来，对研发和平台公司的定向投资加强了拜耳的早期和晚期研发管线。随着Vividion收购Tavros Therapeutics，拜耳继续利用其化学蛋白质组学技术平台，通过精确的小分子疗法，解锁传统上难以成药的靶点。拜耳已经启动了口服KEAP1激活剂在实体瘤中的I期临床试验和口服STAT3抑制剂在实体瘤和血液恶性肿瘤中的I期临床试验，并且还拥有包括针对RAS驱动癌症的RAS-PIK3CA项目在内的新药临床试验申请（IND）支持项目。加强心血管研发管线在心血管疾病领域，拜耳正在推进处于II期临床的治疗药物。用于慢性肾病（CKD）患者的可溶性鸟苷酸环化酶（sGC）激活剂BAY 3283142已进入II期临床。通过血红素非依赖性途径调节sGC，该在研sGC激活剂代表了一类新药，可能在糖尿病肾病等高氧化应激条件下提供优势。通过抗α2抗纤溶酶抗体项目，拜耳正在开发一种基于新模式和作用机制的溶栓剂。这种抗体特异性阻断内源性纤溶酶抑制剂α2AP能够在不增加出血风险的情况下溶解急性栓塞或血栓。目前，这种在研抗体正在针对深静脉血栓形成患者进行II期临床试验评估，并有可能成为具有高度医学相关性的适应症的治疗选择。AB-1002基因疗法目前正在进行一项国际II期临床试验，旨在评估其在治疗充血性心衰（CHF）中的有效性，涉及患有非缺血性心肌病和纽约心脏病协会（NYHA）III级心衰症状且射血分数降低的成年人。关于拜耳拜耳作为一家跨国企业，在生命科学领域的医疗健康与农业方面具有核心竞争力。秉承“共享健康，消除饥饿”的使命，公司致力于通过产品和服务，帮助人们克服全球人口不断增长和老龄化带来的重大挑战，造福人类和地球繁荣发展。拜耳致力于推动可持续发展并对业务产生积极影响。同时，集团还通过科技创新和业务增长来提升盈利能力并创造价值。在全球，拜耳品牌代表着可信、可靠及优质。在2024财年，拜耳的员工人数约为93,000名，销售额为466亿欧元。不计特殊项目的研究开发投入为62亿欧元。更多信息请见www.bayer.com。前瞻性声明本新闻稿包括拜耳集团管理层基于当前设想和预测所作的前瞻性声明。各种已知和未知的风险、不确定性和其它因素均可能导致公司未来的实际运营结果、财务状况、发展或业绩与上述前瞻性表述中所作出的估计产生重大差异。这些因素包括在拜耳官方网站http://www.bayer.com/上公开的拜耳各项报告。本公司没有责任更新这些前瞻性声明或使其符合未来发生的事件或发展。

iStock, Love Employee While Novartis and Bayer got there first, AstraZeneca, Bristol Myers Squibb and Eli Lilly are all vying to bring their radiopharmaceutical assets to a market projected to be worth over $13 billion by 2033. When the FDA approved a small and peculiar eight-amino acid peptide therapy in 2018, it also signed off on a field that today provides a precise and personalized approach to treating cancer. Novartis’ Lutathera belongs to a class called radiopharmaceuticals, which combines a radioactive substance and a biological agent into one therapeutic molecule. Lutathera carries lutetium-177, a beta-emitting isotope of lutetium that releases high-energy radiation as it degrades, in turn damaging a cancer cell’s DNA and ultimately leading to its death. Meanwhile, the drug’s eight-residue backbone allows it to specifically home in on subtype 2 somatostatin receptors, proteins typically highly expressed on specific types of cancer cells. This specific structure gives Lutathera—and radiotherapies more broadly—their characteristic precision. Radiopharmaceutical drugs “can generally shrink tumors effectively without causing much side effects,” Andrew Tsai, an analyst at Jefferies, told BioSpace in an email. The use of radioisotopes gives this modality its marked efficacy, Tsai continued, adding that these treatments might also lead to a more durable, longer-lasting therapy. “Lethality of radiation on cancer is robust, and there is no resistance mechanism to the modality,” he explained. Of course, the use of radioactive agents, no matter how targeted, is still bound to cause some toxicity. According to Tsai, radiotherapies can lead to the accumulation of radiation in various organs, which “could limit the dosing potential” of the modality. There is also a limit to how precise radiopharmaceuticals can get, and they still sometimes lead to unintended off-target side effects such as dry mouth and alopecia. On a more practical level, supply constraints also pose a roadblock to radiopharmaceuticals. “Having access to radioisotope[s] has been rate limiting in many instances even for clinical trials,” Tsai said. Another barrier, he continued, is that the practice has yet to penetrate sufficiently into current medical practice; both patients and physicians remain uninformed or uncomfortable about the tech, and there is a need to improve their awareness. Here, BioSpace looks at the current state of radiopharmaceuticals through five leading players—Novartis, AstraZeneca, Bristol Myers Squibb, Eli Lilly and Bayer—including their strategic moves and key upcoming milestones in a space projected to be worth more than $13 billion by 2033. Novartis Seeks to Maintain Radiopharma Leadership Radiopharma assets: Lutathera, Pluvicto Novartis is the clear frontrunner in the radiopharmaceutical race. The Swiss drugmaker already has two commercial products on the market: Lutathera, indicated for gastroenteropancreatic neuroendocrine tumors (GEP-NETs), and Pluvicto, for metastatic castration-resistant prostate cancer (mCRPC). Compared with its competitors, Novartis has also fleshed out “industry-leading radioligand research and production sites” globally, Geoff Towle, vice president of the company’s radioligand therapy solid tumor strategy, told BioSpace in an email. Despite enjoying a comfortable lead, Novartis continues to strengthen its radiopharma portfolio. In May 2024, the company paid $1 billion to acquire Mariana Oncology and its promising pipeline, anchored by MC-339, an actinium-based therapy being studied in small cell lung cancer (SCLC). Novartis also recently launched two pivotal trials for the next-generation radiotherapy AAA817, which is under development for prostate cancer, Towle shared. Like Pluvicto, AAA817 targets the prostate-specific membrane antigen (PSMA) but instead carries an actinium-based payload, which could deliver higher potency . Aside from building out the pipeline, Novartis is also seeking to expand the indications for its current products. Pluvicto, for instance, is currently under review by the FDA for use in earlier-stage mCRPC, with a regulatory verdict expected in the first half of 2025 , Towle said. This approval, if granted, would allow the use of Pluvicto ahead of chemotherapy and would highlight the “potential for radioligand therapy to become an established pillar of cancer care,” he added. These strategic moves, according to Towle, place the company in a strong position to “realize the $10 billion business potential of our candidates in clinical trials or pre-clinical trials,” and bring radioligand therapies beyond prostate and neuroendocrine tumors to other areas of high unmet patient need, including breast and lung cancer. AstraZeneca Zeroes in on Radioconjugates Radiopharma assets: FPI-2265, AZD2068 AstraZeneca bought entry into the radiopharma market in March 2024, with the up to $2.4 billion acquisition of Fusion Pharmaceuticals. Despite being a relative newcomer to the space, AstraZeneca has set its sights high. In a company presentation last month, the pharma announced that radioconjugates are expected to be a strong driver of its business by 2030 and beyond. “Our aim is to build a substantial radioconjugate portfolio to offer treatment options for patients with a broad range of tumor types,” Puja Sapra, AstraZeneca’s senior vice president for biologics engineering and oncology target discovery, told BioSpace in an email. In particular, the pharma envisions that radioconjugates will complement existing radiation therapy and help reach other cancer types that have been difficult to treat. AstraZeneca’s radiopharma pipeline is anchored by FPI-2265—the centerpiece of the Fusion acquisition—which consists of a small molecule drug that targets PSMA and carries an actinium-225 radioisotope that can inflict irreparable damage to cancer cells. FPI-2265 is being assessed in the Phase II AlphaBreak study in patients with PSMA-positive mCRPC, with a readout expected in the second half of 2025, according to Sapra. AstraZeneca is also working on AZD2068, another radioconjugate from Fusion, designed to target cells expressing the EGFR and cMET markers. The asset is currently in a Phase I study for advanced solid tumors. Findings are expected in 2026 at the earliest, according to the pharma’s latest pipeline document. Aside from its pipeline, AstraZeneca is also working on “molecular imaging and computation pathology,” which according to Sapra would “enhance the delivery and monitoring” of radioconjugates. The end goal, she continued, is to “deliver the right treatment to the right patient.” BMS Leads the Way in Actinium-Based Radiotherapies Radiopharma assets: RYZ-101, RYZ-801 A few months ahead of AstraZeneca, Bristol Myers Squibb made a major radiopharma play in December 2023 with the acquisition of RayzeBio and its actinium-225-based platform for $4.1 billion. “RayzeBio is pioneering the use of Actinium-225,” which is an alpha-emitting radioisotope, Ben Hickey, the company’s president under BMS, told BioSpace in an email. “We believe alpha-emitting isotopes represent the next generation of therapeutic radionucleotides due to their higher potency as compared to beta-emitting isotopes.” Novartis’ Lutathera and Pluvicto carry beta-emitting lutetium-177. With the RayzeBio acquisition, BMS gained ownership of the biotech’s lead asset RYZ-101, which targets somatostatin receptor type 2, a protein commonly expressed on certain solid tumors. BMS is running three clinical trials for RYZ-101: A Phase III study for GEP-NETs and Phase I studies in unresectable metastatic breast cancer and extensive-stage SCLC. The SCLC study will read out later this year , while pivotal data for GEP-NETs are expected in 2026, according to Hickey. “If successful, we believe RYZ101 could be the first [actinium-255-based radiopharmaceutical therapy] approved In the U.S.” BMS is also advancing RYZ-801 , which consists of a proprietary peptide bound to an actinium-225 radioactive payload. RYZ-801, which targets the GPC3 protein, entered the clinic late last year for hepatocellular carcinoma, with enrollment currently ongoing, according to Hickey. Aside from these two clinical assets, the acquisition of RayzeBio gave BMS what Hickey called an “IND-generating engine” that can produce “several therapeutic candidates in the coming years.” BMS currently has several preclinical programs ongoing, he said. Beyond beefing up its radiopharma pipeline, BMS is also building up manufacturing capabilities. Hickey said the pharma’s facility in Indianapolis “is now fully operational” and can contribute to clinical supply, while BMS works to ramp up the site to support commercial-scale operations. Eli Lilly Enters Radiopharma Space With Dealmaking Flurry Radiopharma asset: PNT2001 and PNT2002 Ahead of both BMS and AstraZeneca, Lilly entered the radiopharma arena in October 2023 with $1.4 billion to acquire Point Biopharma—a transaction that formally closed in December that year. Less than a year later, in May 2024, Lilly doubled down on radiopharma with an agreement with Aktis Oncology worth up to $1.1 billion. The deal gave Lilly access to the biotech’s proprietary discovery engine to develop novel radiotherapeutic assets against certain cancer targets. But Lilly wasn’t done. In July 2024, the company entered into another strategic alliance , this time with Radionetics Oncology, for $140 million upfront. The partners will work on radiotherapies targeting small-molecule G-protein coupled receptors for the treatment of various solid tumors. Under the deal, Lilly also has the exclusive right to acquire Radionetics for $1 billion. From the Point acquisition, Lilly gained ownership of the biotech’s lead asset PNT2002, a PSMA-targeted lutetium-177-based therapy being proposed for patients with mCRPC whose disease has progressed after hormonal treatment. A Phase III readout in December 2023 for PNT2002 was disappointing : The asset reduced the risk of death or disease progression by 29% versus androgen receptor blockage—an effect that met statistical significance but fell below what analysts had hoped for. Regulatory filings for PNT2002 are “pending,” according to Jefferies’ Tsai. Lilly has other radiopharma bets in the clinic, including PNT2001, which targets the PSMA protein and carries a 225-actinium radioisotope payload. The asset is currently in Phase I development for prostate cancer. According to a Feb. 7 Jefferies note, Lilly also has a preclinical radiopharma candidate that uses 225-actinium. Another, PNT2003, delivers lutetium-177 and targets the somatostatin receptor to address GEP-NETs. Bayer Builds Radiopharma Pipeline Beyond Xofigo Radiopharma assets: Xofigo, 225Ac-Pelgifatamab, 225Ac-PSMA-Trillium Aside from Novartis, the only other company on this list with an FDA-approved radiopharma asset is Bayer. Xofigo , a radium-223 dichloride radioactive drug, was cleared by the FDA in 2013 for the treatment of castration-resistant prostate cancer with symptomatic bone metastases and with no known visceral metastatic disease. Unlike Novartis’ Lutathera and Pluvicto, however, Xofigo does not include a targeting moiety. Instead, the drug takes advantage of radium’s chemistry, which allows it to bind to bone minerals, in turn helping localize the drug to sites of high bone turnover. Xofigo’s market performance has been underwhelming, peaking at €408 million in 2017 . Bayer did not report specific sales for Xofigo last year. But the pharma is attempting to carve out a space in today’s radiopharma space, inking a strategic collaboration with Bicycle Therapeutics in May 2023. For $45 million upfront and up to $1.7 billion in milestones, Bayer gained access to Bicycle’s proprietary peptides, which it will use to develop targeted radiotherapies for several undisclosed cancer targets. As per its pipeline page , Bayer has at least two clinical-stage radiopharmaceutical therapies in development: 225Ac-Pelgifatamab and 225Ac-PSMA-Trillium, both actinium-based candidates in early-stage studies for advanced prostate cancer.