CYP17A1

刚刚，强生发布公告，旗下创新治疗药物泽倍珂（尼拉帕利阿比特龙片）正式获得国家药品监督管理局批准。作为目前国内首个且唯一获批的双效复方制剂，泽倍珂联合泼尼松或泼尼松龙用于治疗携带胚系和/或体系 BRCA 基因突变的转移性去势抵抗性前列腺癌成人患者（mCRPC）。 泽倍珂®是每日一次的口服复方制剂，用于联合泼尼松或泼尼松龙一线治疗携带BRCA1/2突变的转移性去势抵抗性前列腺癌成人患者，临床证实其相较标准治疗可显著延长影像学无进展生存期。 近年来，中国前列腺癌的发病率显著上升。据国家癌症中心最新发布的2022年度中国恶性肿瘤疾病负担报告显示，我国前列腺癌的发病率为每10万人中18.61例，已成为男性泌尿生殖系统中最常见的肿瘤。 泽倍珂®是BRCA1/2突变mCRPC成人患者的一线靶向治疗方案。作为一种高选择性聚腺苷二磷酸核糖聚合酶(PARP)抑制剂，尼拉帕利和醋酸阿比特龙的组合联合泼尼松或泼尼松龙，能够靶向mCRPC患者的两种致癌驱动因素——雄激素受体轴和BRCA1/2突变。 经临床验证，泽倍珂®联合泼尼松或泼尼松龙可显著延长BRCA1/2突变mCRPC患者的影像学无进展生存期（rPFS）。此外，与安慰剂相比，尼拉帕利还显示出总体生存 (OS)改善的趋势，可显著延长至症状进展时间（TSP）和至细胞毒性化疗起始时间（TCC），同时并维持了患者的生活质量。 内容来源于网络，如有侵权，请联系删除。

GLP-1减肥药市场已步入更为紧张刺激的下半场：一边是礼来与诺和诺德两大巨头，在临床试验、产能扩张及商业化上展开了全方位的激烈比拼；另一边，中国药企也在纷纷加速研发步伐，通过提高药物疗效和差异化设计突围。 与此同时，新型减肥药正悄然崛起成为新的蓝海。其中，ActRII靶向药物凭借既减重又增肌的独特疗效脱颖而出。 近日更是喜报频传：礼来启动了Bimagrumab联合替尔泊肽增肌减脂的Ⅱ期临床试验；来凯医药的LAE102临床试验也取得重大进展，且公司股价因此暴涨近40%。 来凯医药，这个看似边缘的Biotech，正以其不俗实力，吸引着市场的高度关注和期待。 01 下一代减肥药崛起 GLP-1靶点的减肥药是这两年最火爆的赛道之一，两大巨头礼来、诺和诺德均实现业绩、股价双双“暴增”。 更重要的是，下一代全球“药王”有望在GLP-1减肥药赛道诞生。 2024年上半年，诺和诺德的司美格鲁肽销售额高达129亿美元，同比增长43%，紧逼现任全球“药王”K药（142亿美元，同比增长21%）；同期，礼来的替尔泊肽销售额达66.56亿美元，同比增长329%。 按减重适应症看，司美格鲁肽减重版注射制剂Wegovy销售额为30.8亿美元，同比增长74%；替尔泊肽减重版Zepbound销售额为17.6亿美元。 不过，GLP-1减肥药并非完美，在减去脂肪的同时也使得肌肉流失，出现市场热议的“司美格鲁肽脸”（面部凹陷、皮肤松弛）。 在此背景下，减脂增肌靶点成为了新的竞技场，包括ActRII、艾帕素（Apelin）、HIF2等。其中，ActRII是在脂肪和肌肉细胞中都表达的激活素受体，通过阻断ActRII通路可促进肌肉再生和减少脂肪。 由此，具备减重增肌效果的ActRII单抗应运而生，再加上减肥药市场拥有巨大潜力，市场将ActRII誉为继GLP-1后又一个减重靶点“金矿”，吸引着资本市场的目光。 10月16日，来凯医药宣布其自研、全球首创的ActRIIA单抗LAE102，针对超重/肥胖在中国开展的I期临床试验取得重大进展：单次剂量递增研究的皮下注射部分已启动。 消息一出，踩在风口上的来凯医药，在短短3个交易日股价暴涨近40%，足见市场对“下一代减肥药新星”的高度期待。 股价暴涨背后的另一推动因素，还得益于礼来宣布启动Bimagrumab联合替尔泊肽增肌减脂的II期临床试验。尤其是，目前全球进入临床阶段的ActRII靶向药物（针对超重/肥胖）仅有少数几款，显著推升了来凯医药的内在价值。 02 三箭齐发，抢占先机 在ActRII靶向药物研发这条道路上，礼来与来凯医药走在了前头。 其中，礼来在2023年7月以近20亿美元重金收购Versanis，拿下其主要资产Bimagrumab（ActRIIA/B单抗）；来凯医药则一口气布局了3款ActRII靶向药物，包括LAE102（ActRIIA单抗）、LAE103（ActRIIB单抗）和LAE123（ActRIIA/B单抗），这一前瞻性的策略，为其在未来的市场竞争中赢得了先机。 从临床进度看，礼来的Bimagrumab进展更快，目前正在进行临床IIb期BELIEVE研究，旨在评估其单药或联合司美格鲁肽治疗48周后在超重或肥胖的成年人中的效果。 根据此前披露的II期试验数据显示：接受Bimagrumab治疗48周后，患者的的全身脂肪量减少了20.5%，肌肉量增加了3.6%，代谢指标也得到改善。 与GLP-1药物联用，发挥更大的疗效，使得ActRII靶向药成为GLP-1最佳“减重伴侣”药物之一。目前，礼来正在进行联用策略的临床验证，期待后续数据读出。 ActRII赛道仍处于蓝海阶段，来凯医药正在打造差异化的竞争优势。 首发管线LAE102，目前均已在中国和美国获批开展针对肥胖适应症的I期临床试验。此前已在临床前研究显示出增加肌肉并减少脂肪的效果。 另外，鉴于ActRII具有治疗肌肉疾病、肥胖、糖尿病以及癌症的潜力，来凯医药计划探索LAE102用于更多适应症。其中，LAE102用于治疗患者数量庞大的非小细胞肺癌（NSCLC），已于2023年5月获FDA批准开展临床试验。 就减重适应症而言，来凯医药正在开展的I期临床系一项随机、双盲、安慰剂对照、单次和多次给药剂量递增研究，旨在通过静脉输注和皮下注射两种给药方式，评价LAE102注射液在健康成年受试者及超重/肥胖受试者中的安全性、耐受性及药代动力学。 截至2024年9月30日，已有过半数的静脉输注队列完成了给药，并在低剂量组中就观察到靶点结合的早期迹象和预期的PD生物标志物变化。近日，来凯医药宣布启动单次剂量递增研究的皮下注射部分，2024年底前有望完成该项研究。 来凯医药董事长兼CEO吕向阳博士表示，“与静脉注射给药相比，皮下给药对慢性病患者长期使用更有优势，也更易与GLP-1受体激动剂联合用药。”LAE102与GLP-1受体激动剂联用，可进一步减少脂肪，并显著降低GLP-1受体激动剂导致的肌肉流失。 目前，越来越多Biotech达成license out、实现出海，来凯医药LAE102从一开始便瞄准国际市场、向美国FDA提交临床试验申请，或许也是为了给后续BD交易铺路。 03 BD预期打满 实际上，来凯医药不只有ActRII靶向药物这些管线，也不仅仅布局纤维化、代谢疾病领域，更值得关注的重头戏还有针对癌症的丰富管线。 截至目前，来凯医药已在癌症领域布局了10个管线，其中小分子药物和大分子药物各5个，涵盖AKT、CYP17A/CYP11B2、PI3Ka、PARP1等各种前沿靶点，进度最快的是LAE002和LAE001。 来凯医药的研发管线 图片来源：公司官网 LAE002（Afuresertib）是一种AKT强效抑制剂，抑制所有三种AKT亚型（AKT1、AKT2及AKT3），也是全球仅有的2种处于晚期临床开发阶段的针对乳腺癌及前列腺癌的AKT抑制剂之一。 AKT抑制剂是极具潜力的蓝海赛道，目前全球仅有阿斯利康的Capivasertib获批上市，科睿唯安预测该药到2031年将在七国集团市场实现销售额超10亿美元，也有海外分析师预测该药的销售峰值可达38亿美元。 目前，来凯医药正在开展LAE002针对乳腺癌、前列腺癌、卵巢癌及PD-1/PD-L1耐药实体瘤的多项临床试验，其中已有3项研究处于临床后期阶段。根据公开数据，与其他AKT抑制剂相比，LAE002具有疗效更高、药效更好、肿瘤抑制暴露更显著、安全性更佳等多项优势，具备BIC潜质。 根据弗若斯特沙利文的资料，全球及中国的乳腺癌发病人数预计到2030年将达到266.64万人及37.24万人。估计中国60%以上的乳腺癌患者存在HR+/HER2-分子特征，针对这类疾病的一线及/或二线疗法是内分泌/抗雌激素疗法联合CDK4/6抑制剂。 然而，15%至20%的患者对治疗产生原发性耐药，而另外30%至40%的患者会随时间对治疗产生耐药性。CDK4/6抑制剂及内分泌治疗后的HR+/HER2-乳腺癌仍是一个巨大的未满足医疗需求，具有数十亿美元的市场潜力。 今年5月，来凯医药在中国启动了LAE002联合氟维司群治疗PIK3CA/AKT1/PTEN改变的HR+/HER2-局部晚期或转移性乳腺癌III期临床试验AFFIRM-205。 值得关注的管线还有LAE001，作为全球首款CYP17A1/CYP11B2双靶点抑制剂，具备比CYP17A1抑制剂阿比特龙更优的有效性和安全性。 今年5月，FDA批准了LAE002联合LAE001治疗转移性去势抵抗性前列腺癌（mCRPC）患者的III期临床试验。此前，该组合疗法展现出了惊艳的疗效。 据II期临床数据显示：截至2023年11月21日，40名在接受1-3线标准治疗（包括至少接受过1线阿比特龙或第二代AR拮抗剂治疗）后病情进展的患者已加入推荐的II期剂量组，中位rPFS为8.1个月。与过去接受标准治疗的mCRPC患者2到4个月的中位rPFS相比，是一个显著的改善。 可以说，LAE002和LAE001都具备磅礴的BD预期。实际上，来凯医药也正在寻求战略合作伙伴，加速两者的开发和商业化。 04 结语 尽管作为小型Biotech，来凯医药却展现出了显著的内在价值，手握两款全球前二的潜力管线。这些管线的临床进展与满满的BD预期相互呼应，有望为来凯医药闯出一番天地。 参考资料 1.各家公司的财报、公告、官微 2.《减脂又增肌！礼来正式启动Bima+替尔泊肽增肌减脂2期临床》，GLP1减重宝典 3.中邮证券、华创证券研报

Metastatic castration-sensitive prostate cancer (mCSPC), also known as metastatic hormone-sensitive prostate cancer (mHSPC), refers to prostate cancer that has spread beyond the prostate but still responds to therapies that lower testosterone (castration) with an aging population, the incidence of prostate cancer is rising, leading to an increased demand for advanced therapies to treat metastatic forms of the disease. LAS VEGAS, Oct. 15, 2024 /PRNewswire/ -- DelveInsight's ' Metastatic Castration-Sensitive Prostate Cancer Pipeline Insight 2024 ' report provides comprehensive global coverage of pipeline mCSPC therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the mCSPC pipeline domain. Key Takeaways from the Metastatic Castration-Sensitive Prostate Cancer Pipeline Report DelveInsight's mCSPC pipeline report depicts a robust space with 35+ active players working to develop 40+ pipeline therapies for mCSPC treatment. Key mCSPC companies such as Tavanta Therapeutics, AstraZeneca, Regeneron Pharmaceuticals, Astellas Pharma, Propella Therapeutics, POINT Biopharma, Amgen, Janssen Research & Development, LLC, Bayer, Beigene, Amgen, Merck Sharp & Dohme LLC, Jiangsu HengRui Medicine Co., Ltd., Suzhou Kintor Pharmaceutical Inc, Astellas Pharma, and others are evaluating new mCSPC drugs to improve the treatment landscape. Promising mCSPC pipeline therapies such as TAVT-45 (abiraterone acetate), Saruparib (AZD5305), Capivasertib, REGN2810, Abiraterone decanote + dexamethasone or prednisone (PRL-02/ASP5541), [Ac-225]-PSMA-62, Xaluritamig, Apalutamide, Darolutamide, Luteinizing Hormone Releasing Hormone, Pembrolizumab, Dalpiciclib isethionate, GT0918, PRL-02, and others are under different phases of mCSPC clinical trials. In October 2024, Apalutamide (Erleada) was found to provide a significant improvement in overall survival (OS) at 24 months compared with enzalutamide (Xtandi) in the treatment of androgen receptor pathway inhibitor (ARPI)-naïve patients with metastatic castration-sensitive prostate cancer (mCSPC). In April 2024, Saruparib (AZD5305) demonstrated encouraging efficacy, favorable safety, a wide therapeutic index, and improved pharmacokinetic properties compared with currently approved PARP inhibitors in patients with advanced solid tumors harboring BRCA1/2, PALB2, or RAD51C/D mutations, according to findings from the Phase I/IIa PETRA study. In February 2024, Capivasertib combined with docetaxel to enhance anti-tumour activity through inhibition of AKT-mediated survival mechanisms in prostate cancer. Capivasertib can enhance anti-tumour effects of docetaxel by targeting residual docetaxel-persister cells, independent of PTEN status, to induce apoptosis and DNA damage in part through GSK3β. In January 2023, Tavanta Therapeutics announced positive top-line results from its pivotal, global Phase III clinical trial, evaluating the safety and efficacy of TAVT-45 (abiraterone acetate). The trial met its primary objective of establishing therapeutic equivalence of TAVT-45 to Zytiga® in patients with metastatic castrate-resistant prostate cancer (mCRPC) and metastatic high-risk castrate-sensitive prostate cancer (mCSPC), in addition to demonstrating a comparable safety profile. Request a sample and discover the recent advances in mCSPC treatment drugs @ Metastatic Castration-Sensitive Prostate Cancer Pipeline Report The mCSPC pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage mCSPC drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the mCSPC clinical trial landscape. Metastatic Castration-Sensitive Prostate Cancer Overview Metastatic castration-sensitive prostate cancer (mCSPC) is an advanced form of prostate cancer in which the cancer cells have spread beyond the prostate to other parts of the body, such as bones or lymph nodes, but remain responsive to hormone therapy. This means that reducing testosterone levels can still effectively slow the growth of cancer cells. mCSPC often arises when prostate cancer is initially diagnosed or when early-stage prostate cancer recurs after treatment. It is distinct from castration-resistant prostate cancer (CRPC), where the cancer continues to progress despite low testosterone levels. The causes of mCSPC primarily involve the spread of prostate cancer cells beyond the local prostate region, a process called metastasis. Although the exact mechanisms are complex, certain risk factors increase the likelihood of developing prostate cancer and its progression to metastatic disease. These risk factors include advanced age, a family history of prostate cancer, genetic mutations such as BRCA1/BRCA2, and race. Symptoms of mCSPC can include bone pain, urinary issues, fatigue, weight loss, and general malaise, especially if the cancer has spread to bones or lymph nodes. However, in many cases, early stages of metastasis may be asymptomatic, making regular screening essential for those at risk. Diagnosis of mCSPC typically involves a combination of blood tests, such as measuring prostate-specific antigen (PSA) levels, imaging studies, and biopsy to confirm the presence of cancer cells. Treatment for mCSPC revolves around androgen deprivation therapy to lower testosterone levels, often combined with other agents like chemotherapy (e.g., docetaxel) or second-generation androgen receptor inhibitors (e.g., abiraterone or enzalutamide). In recent years, clinical trials have shown the benefit of combining ADT with novel therapies to improve survival rates and manage symptoms, with personalized treatment approaches based on genetic testing becoming more common. Find out more about mCSPC treatment drugs @ Drugs for Metastatic Castration-Sensitive Prostate Cancer Treatment A snapshot of the mCSPC Pipeline Drugs mentioned in the report: Learn more about the emerging mCSPC pipeline therapies @ Metastatic Castration-Sensitive Prostate Cancer Clinical Trials Metastatic Castration-Sensitive Prostate Cancer Therapeutics Assessment The mCSPC pipeline report proffers an integral view of the mCSPC emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Metastatic Castration-Sensitive Prostate Cancer Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Therapeutics Assessment By Route of Administration: Oral, Intravenous, Subcutaneous Therapeutics Assessment By Molecule Type: Small molecule, Cell therapy, Peptides, Polymer, Small molecule, Gene therapy Therapeutics Assessment By Mechanism of Action: Steroidal inhibitor of CYP17A1, PARP1 inhibitor, Proto-oncogene protein c-akt inhibitors, CYP17 lyase inhibitor, Antibody-dependent cell cytotoxicity, Immunostimulants, T lymphocyte stimulants, Ionizing radiation emitters. Key Metastatic Castration-Sensitive Prostate Cancer Companies: Tavanta Therapeutics, AstraZeneca, Regeneron Pharmaceuticals, Astellas Pharma, Propella Therapeutics, POINT Biopharma, Amgen, Janssen Research & Development, LLC, Bayer, Beigene, Amgen, Merck Sharp & Dohme LLC, Jiangsu HengRui Medicine Co., Ltd., Suzhou Kintor Pharmaceutical Inc, Astellas Pharma, and others. Key Metastatic Castration-Sensitive Prostate Cancer Pipeline Therapies: TAVT-45 (abiraterone acetate), Saruparib (AZD5305), Capivasertib, REGN2810, Abiraterone decanote + dexamethasone or prednisone (PRL-02/ASP5541), [Ac-225]-PSMA-62, Xaluritamig, Apalutamide, Darolutamide, Luteinizing Hormone Releasing Hormone, Pembrolizumab, Dalpiciclib isethionate, GT0918, PRL-02, and others. Dive deep into rich insights for new drugs for mCSPC treatment, visit @ Metastatic Castration-Sensitive Prostate Cancer Drugs Table of Contents For further information on the mCSPC Cancer pipeline therapeutics, reach out @ Metastatic Castration-Sensitive Prostate Cancer Treatment Drugs Related Reports Metastatic Castration-Sensitive Prostate Cancer Market Metastatic Castration-Sensitive Prostate Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key mCSPC companies including Myovant Sciences, Pfizer, Bayer, Orion, Novartis, AstraZeneca, Pfizer, Janssen, Merck, Eli Lilly, among others. Metastatic Prostate Cancer Market Metastatic Prostate Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key metastatic prostate cancer companies including AstraZeneca, Arvinas, Madison Vaccines, Phosplatin Therapeutics, Hinova Pharmaceuticals, Bristol Myers Squibb, Merck, MacroGenics, Daiichi Sankyo, Seagen, Taiho Pharmaceutical, Modra Pharmaceuticals, Xencor, Point Biopharma, Lantheus Holdings, Zenith Epigenetics, Essa Pharma, Telix Pharmaceuticals, Kintor Pharmaceutical, AB Science, Eli Lilly and Company, Exelixis among others. Metastatic Castration-Resistant Prostate Cancer Market Metastatic Castration-Resistant Prostate Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key mCRPC companies including AstraZeneca, Merck Sharp & Dohme, Hinova Pharmaceuticals, Pfizer, Astellas Pharma, Modra Pharmaceuticals, AB Science, Eli Lilly and Company, Zr Pharma & GmbH, Bristol-Myers Squibb, Ipsen, Exelixis, Takeda, Janssen Research & Development, Tesaro, Lantheus Holdings, Kintor Pharmaceutical, MacroGenics, Daiichi Sankyo, Madison Vaccines, Novartis, Point Biopharma, Xencor, Essa Pharma, Telix International, Bayer, Arvinas, among others. Metastatic Castration-Resistant Prostate Cancer Pipeline Metastatic Castration-Resistant Prostate Cancer Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key mCRPC companies, including AstraZeneca, Merck Sharp & Dohme, Hinova Pharmaceuticals, Pfizer, Astellas Pharma, Modra Pharmaceuticals, AB Science, Eli Lilly and Company, Zr Pharma & GmbH, Bristol-Myers Squibb, Ipsen, Exelixis, Takeda, Janssen Research & Development, Tesaro, Lantheus Holdings, Kintor Pharmaceutical, MacroGenics, Daiichi Sankyo, Madison Vaccines, Novartis, Point Biopharma, Xencor, Essa Pharma , Telix International, Bayer, Arvinas, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED