131I-MIP-1095

前列腺癌的病因及发病机制十分复杂，其确切病因尚不明确。目前，前列腺癌早期可以通过手术、放疗、雄激素剥夺疗法(ADT)等进行成功治疗。但前列腺癌早期临床症状不明显，因此确诊时多数患者已属中晚期。近年来，随着一系列突破性进展的取得，前列腺癌药物的江湖纷争出现新的变化。注：本文仅作信息交流之目的，文中观点不代表药智网立场，也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。01治疗方案有限，常见疗法包括化疗和内分泌疗法前列腺是雄激素依赖性器官，其生长发育与雄激素受体（AR）信号通路密切相关。AR在前列腺癌的发生、发展中起重要作用。AR通路抑制剂通过减少循环睾酮及雄激素-AR受体复合物，降低前列腺癌中的AR活性。目前，前列腺癌早期可以通过手术、放疗、雄激素剥夺疗法(ADT)等进行成功治疗。但前列腺癌早期临床症状不明显，因此确诊时多数患者已属中晚期，中晚期前列腺癌患者首选治疗方案为雄激素剥夺治疗(ADT)。ADT是晚期转移性前列腺癌患者的主要全身性基础治疗，也是各种新型联合治疗方案的基础。ADT包括多种实施方案，其中，单纯去势（外科或者药物去势）是最广为接受的核心治疗方式。近年来，出现了一系列突破性进展，主要是ADT与新型内分泌治疗药物或化疗药物的联合使用，改善了转移性前列腺癌的总体治疗效果。但最终，几乎所有患者经ADT治疗18~36个月后会出现药物抵抗，最终进展为去势抵抗性前列腺癌(CRPC)，此阶段的患者中位生存期大约只有12个月。下图为前列腺癌进展到不同阶段的治疗方法及用药方案。注：本文仅作信息交流之目的，文中观点不代表药智网立场，也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。表1 前列腺癌主要治疗药物分类及作用机制数据来源：公开数据，药智咨询整理02第二代AR拮抗剂等新药的上市，刺激前列腺癌市场增长2021年，中国前列腺癌治疗药物市场规模为77.45亿元，2017-2021年复合增长率为14.79%。同时，近年来多个第二代AR拮抗剂在国内上市，包括恩扎卢胺（2019年），阿帕他胺（2020年），瑞维鲁胺（2022年6月）等，预计第二代AR拮抗剂等新药的上市将促进前列腺癌治疗药物市场持续增长。图1 中国前列腺癌治疗药物市场规模数据来源：药智数据，药智咨询整理2021年，中国前列腺癌治疗药物中市场份额最高的为亮丙瑞林（27.16%），其次为戈舍瑞林（23.61%）。这两个药物为GnRHR激动剂，是雄激素剥夺疗法（ADT）中常用的药物，ADT是激素敏感性前列腺癌联合用药的基础，所以市场份额高。阿比特龙是由强生公司开发的CYP17A酶不可逆抑制剂，CYP17A酶是雄激素生物合成过程中的限速酶，存在于睾丸、肾上腺以及前列腺癌细胞中。2011年获FDA批准上市，2015年被美国泌尿外科协会推荐用于治疗各种类型的转移性去势抵抗性前列腺癌（mCRPC）患者，2015年4月在中国获批上市。阿比特龙临床试验疗效显著，2017年进入医保，进入医保后迅速放量，2017-2021年复合增长率高达71.34%。2021年，阿比特龙销售额达13.92亿元，同比2020年增长5.19%。阿比特龙2020年进入国家集采，进入集采后阿比特龙的销售额依然保持增长。恩扎卢胺由Medivation和安斯泰来公司合作开发，2012年获FDA批准用于治疗CRPC，2019年在中国获批上市。恩扎卢胺是第二代非甾体类抗雄激素药物，相比于第一代AR抑制剂仅竞争性地结合AR，其抗AR活性比第一代强数倍。恩扎卢胺是少数无需联合类固醇激素治疗的选择，相较于阿比特龙（需要与泼尼松联用以控制不良反应）具有显著安全性优势。2019年至今在全球抗前列腺癌市场中恩扎卢胺所占市场份额最大；而国内该药于2019年上市，上市后销售额增长迅速，2021市场规模为1.96亿元，同比2020年增长4170.32%，预计未来国内用药结构将向全球看齐，恩扎卢胺将保持高速增长。03在研药物数量多，靶点集中在FOLH1、AR等全球前列腺癌在研治疗药物约657个，中国前列腺癌在研治疗药物约145个；全球在研靶点集中在PSMA（FOLH1）、AR、GnRH receptor等靶点。图2 全球及中国前列腺癌治疗上市在研药物数量和靶点图片来源：药智数据-全球药物分析系统前列腺特异性膜抗原（PSMA,又称叶酸水解酶1（FOLH1））是一种跨膜糖蛋白，目前的研究表明PSMA在超过90%的前列腺癌细胞表面都出现了过表达，并且在晚期和去势抵抗性患者的癌细胞中表达水平更高。可通过影像学评估PSMA的表达情况，与传统的扫描检查相比，PSMA PET/CT在检测前列腺癌病灶方面有着独特的优势，在前列腺癌早期和病程分期上能做出更有效的判断，PSMA PET/CT凭借其高特异性多模态显像的优势显著提高诊断敏感性和准确性。目前上市和在研的PSMA药物多是放射性药物，包括已上市药物177Lu-PSMA-617，和在研药物PNT2002（177Lu标记的放射性药物）、131I-MIP-1095（131I标记的放射性药物）、225Ac-PSMA-I&T（225Ac标记的放射性药物）等。其中，诺华研发的放射性配体疗法（177Lu-PSMA-617）于2022年3月获FDA批准，治疗范围包括已扩散的、接受过其他治疗的前列腺癌患者。177Lu-PSMA-617包括靶向性化合物（PSMA-617）和治疗性同位素（177Lu），能够实现精准癌症治疗。177Lu-PSMA-617与表达PSMA的前列腺癌细胞结合，反射性元素产生的放射线更集中在肿瘤组织局部，在杀死癌细胞的同时减少对健康细胞的损伤。目前，mCRPC一线治疗主要推荐优选新型内分泌治疗（NHT），国内可及的方案有恩扎卢胺、阿比特龙等。但临床结果发现新型内分泌治疗药物并不是对所有的去势抵抗性前列腺癌（CRPC）都有效，一部分患者对这些药物存在原发性耐药，对于初始有效的mCRPC患者，最终也还是发生继发性耐药。耐药机制主要是由于AR基因发生变异，包括AR扩增、AR突变、AR剪切变异体（ARVs）等。沉默AR基因表达的治疗策略是治疗CRPC的潜在有效方法。反义寡核苷酸（ASO）可以从本质上阻断特定基因靶标，阻止其相关蛋白质的合成，因此已成为多种人类疾病的替代治疗方法。阿斯利康开发了反义核苷酸AZD5321，临床前研究表明，AZD5312与AR mRNA杂交，从而阻断AR蛋白的翻译，能够有效抑制全长AR(AR-FL)及其剪接变体的表达，这既能抑制AR诱导的肿瘤细胞生长，又能促进AR过表达的肿瘤细胞凋亡，从而在恩杂鲁胺耐药的CRPC模型中产生抗肿瘤活性。但该药物于2014年开始进行I期临床试验，目前暂无进展。04小结目前针对晚期前列腺癌治疗通路有限，深受现有治疗方案交叉耐药的瓶颈；mCRPC的中位生存时长短，患者往往进展到二线治疗时丧失治疗积极性，存在巨大未被满足的临床需求。亟需一个全新的治疗方式和理念，带领临床患者走出治疗困境。注：本文仅作信息交流之目的，文中观点不代表药智网立场，也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。参考文献：[1]闵淑慧，胡依，郭芮绮.1990-2019年中国前列腺癌疾病负担分析及趋势预测.中国肿瘤ISSN 1004-0242，CN 11-2859/R.[2]http://www.phirda.com/artilce_27200.html?cId=1[3]De Velasco MA,Kura Y,Sakai K,Hatanaka Y,Davies BR,Campbell H,Klein S,Kim Y,MacLeod AR,Sugimoto K,Yoshikawa K,Nishio K,Uemura H.Targeting castration-resistant prostate cancer with androgen receptor antisense oligonucleotide therapy.JCI Insight.2019 Sep 5;4(17):e122688.声明：本内容为作者独立观点，不代表药智网立场。如需转载，请务必注明文章作者和来源。对本文有异议或投诉，请联系maxuelian@yaozh.com。责任编辑 | 八斤转载开白 | 马老师 18996384680（同微信）如需定制医药咨询服务，请扫描下方二维码咨询！ 阅读原文，是受欢迎的文章哦

The dynamics of the metastatic prostate cancer market are anticipated to change in the coming years owing to the rise in the number of companies taking interest in the development of specific drugs for mCRPC and nmCRPC along with increasing awareness and penetration of already approved prostate cancer drugs. LAS VEGAS, Dec. 13, 2023 /PRNewswire/ -- DelveInsight's Metastatic Prostate Cancer Market Insights report includes a comprehensive understanding of current treatment practices, metastatic prostate cancer emerging drugs, market share of individual therapies, and current and forecasted market size from 2019 to 2032, segmented into 7MM [the United States, the EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan]. Key Takeaways from the Metastatic Prostate Cancer Market Report As per DelveInsight analysis, the total market size in the 7MM for metastatic castration-resistant prostate cancer (mCRPC) was estimated to be nearly USD 6.4 billion in 2022, which is expected to show positive growth by 2032. In 2022, the United States held the highest market share for mCRPC and mCSPC in the 7MM, at 63% and 61%, respectively, followed by the EU4 countries and the UK. As per DelveInsight estimates, the total prevalent population of prostate cancer in the 7MM was nearly 8 million cases in 2022. These cases will increase during the study period, i.e., 2019–2032. Leading metastatic prostate cancer companies such as 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, and others are developing novel metastatic prostate cancer drugs that can be available in the metastatic prostate cancer market in the coming years. The promising metastatic prostate cancer therapies in the pipeline include HC-1119, Talazoparib, Enzalutamide, Niraparib, Boosted Oral Docetaxel, Masitinib, EPI-7386, Verzenio, 177Lu-PSMA-617, Capivasertib, I-131-1095, Proxalutamide (GT0918), MGC018, DS-7300, MVI-816, ARV-110, 177Lu-PNT2002 (PNT2002), Vudalimab (XmAb20717), 177Lu-DOTA-rosopatamab (TLX591), and others. Established therapies in the metastatic prostate cancer market include Astella/Pfizer's and Jansenn's blockbuster products XTANDI and ZYTIGA, respectively, approved for metastatic patients for over a decade now. Even though ZYTIGA's generics have entered the US market since 2019, and the EU since late 2022, leading to a drastic decline in the revenue mainly in the US, the product is extensively being evaluated in combination with novel emerging therapies, leading to an increase in patient share on the compound abiraterone acetate. Whereas, Jansenn's XTANDI, the biggest revenue generator in the prostate cancer market, has witnessed stable growth since 2021 owing to increased competition. Quantitatively mCRPC pipeline seems to be quite strong, however with recent failures/terminations of several trials of certain therapies in the past year, we have mentioned the most promising ones, which include ESSA Pharma's EPI-7386, Macrogenics, and Daiichi's anti-B7-H3 Antibody Drug Conjugates, MGC-018 and DS-7300 respectively, Arvinas, AR-targeted PROTAC protein degrader, and Point Biopharma's Radioligand therapy. Except for Point Biopharma's therapy, none of these potential players have initiated a Phase III trial, even though Arvinas is planning to opt for an accelerated approval based on its Phase II data readout. The landscape of mHSPC has evolved tremendously in the past decades. The treatment paradigm has shifted from androgen deprivation therapy (ADT) alone to doublet combinations comprising ADT with docetaxel or an androgen receptor inhibitor, and now triplet therapy involving all three classes of agents. Apart from XTANDI, ZYTIGA, and ERLEADA in the mCSPC market, Bayer's NUBEQA is another rising contender with a strong uptake in a short period. Bayer is further strategizing to increase the prescription by volume for NUBEQA by label expansion in patients who are not eligible for chemotherapy in the ARANOTE Phase III trial. PARP inhibitors such as AKEEGA and TALZENNA are also currently being evaluated in the mHSPC space alone and with ARIs. Novartis' radioligand therapy, PLUVICTO approved in 2022, has generated an unexpected revenue from the third-line mCRPC setting, further plans to expand in an earlier line in mCRPC by 2024 in the United States. The approval of PLUVICTO has also marked a crucial advancement in treating progressive mCRPC, offering improved survival rates for those with limited treatment options. The drug had an exceptionally robust initial market performance, garnering a stronger-than-expected uptake in the US. The drug is currently being studied in the Phase III PSMAddition study to see if that triplet combination is better than ADT and an androgen receptor signaling inhibitor alone in patients with mHSPC. Discover which therapies are expected to grab the major metastatic prostate cancer market share @ Metastatic Prostate Cancer Market Report Metastatic Prostate Cancer Overview Prostate cancer, a form of malignancy specific to the prostate gland within the male reproductive system, can advance to a metastatic stage, spreading from the prostate to other areas of the body. This advanced stage is often referred to as metastatic or advanced prostate cancer, commonly extending to lymph nodes or bones. Prostate cancer symptoms can differ widely among individuals. Although some men might not experience any symptoms, typical signs may include the presence of blood in the urine or semen, painful ejaculation, discomfort or a burning sensation during urination, and various other related symptoms. The primary diagnostic method involves prostate-specific antigen (PSA) testing, which detects elevated PSA levels in individuals affected by prostate cancer or other prostate-related conditions. Screening processes may also include a digital rectal exam to identify any notable prostate tumors, alongside additional methods such as prostate ultrasound and MRI scans. However, a conclusive diagnosis typically necessitates a transrectal ultrasound-guided (TRUS) prostate tissue biopsy. Metastatic Prostate Cancer Epidemiology Segmentation As per DelveInsight analysis, the United States had the highest number of diagnosed prostate cancer cases in 2022, with approximately 2.9 million reported cases. In 2022, total cases of metastatic CSPC/HSPC and metastatic CRPC were around 100K and 120K, respectively, in the 7MM. These cases are expected to increase by 2032. The metastatic prostate cancer market report proffers epidemiological analysis for the study period 2019–2032 in the 7MM segmented into: Total Prevalent Cases of Prostate Cancer Total Diagnosed Cases of Prostate Cancer Age-Specific Cases of Prostate Cancer Total Diagnosed Cases of Prostate Cancer by Clinical Stages Total Metastatic Cases of Prostate Cancer Total Treated Cases of mCRPC Total Treated Cases of mCSPC Metastatic Prostate Cancer Treatment Market Metastatic Castration-Resistant Prostate Cancer (mCRPC) is a stage of prostate cancer that has spread to other parts of the body, such as lymph nodes or bones, and no longer responds to treatment that lowers testosterone. Despite currently approved therapeutics, mCRPC remains a terminal diagnosis with an aggressive disease course. ADT is a stalwart therapy for the initial treatment of metastatic disease. Unfortunately, most men in this situation will go on to develop mCRPC and require secondary systemic therapy. This disease state can be very challenging to treat. Docetaxel was the only agent available for the treatment of mCRPC until 2010, which showed an increase in overall survival compared with the standard of care. It was approved in 2004 for mCRPC with prednisone. Patients failed to first-line docetaxel for many years, and no standard treatment option was approved. However, in the last few years, several drugs such as JEVTANA, ZYTIGA, XTANDI, LYNPARZA, TALZENNA, AKEEGA, and others have received regulatory approval for mCRPC in the United States. Most recently, PARP inhibitors have shown tremendous development in this area with AKEEGA (Janssen), followed by TALZENNA (Pfizer/Astellas Pharma) and LYNPARZA in combination (AstraZeneca/Merck) getting approved in mCRPC in 2023. The approval of PLUVICTO has also marked a crucial advancement in treating progressive mCRPC, offering improved survival rates for those with limited treatment options. The drug had an exceptionally robust initial market performance, garnering a stronger-than-expected uptake in the US. Quantitatively, the mCRPC pipeline seems to be quite strong. ADCs such as MGC018 and DS-7300 have both displayed encouraging results in clinical trials involving patients with mCRPC. However, except for Point Biopharma's therapy, none of these potential players have initiated a Phase III trial, even though Arvinas plans to opt for an accelerated approval based on its Phase II data readout. Metastatic Castrate-Sensitive Prostate Cancer (mCSPC) is an advanced form of cancer in which cancer cells have spread from the prostate to other body areas. However, the patient is still sensitive to androgen deprivation therapy (ADT) (some mCSPC patients have never had ADT, while others may have had ADT but have recovered testicular function). The backbone of all treatments in mCSPC is androgen deprivation therapy (ADT) with medications that suppress the level of testosterone in the body because testosterone is the fuel for prostate cancer and gives the signals to grow and spread. Studies over the last decade have demonstrated that intensification of androgen deprivation with different treatment modalities correlates with prolongation of survival. The options for intensification include docetaxel chemotherapy, different androgen receptor-targeted agents, including abiraterone acetate, apalutamide, and enzalutamide, and radiation to the prostate. Most recently, the treatment paradigm for mHSPC shifted to triplet therapy, NUBEQA combined with ADT and chemotherapy. According to the findings presented at the ASCO GU 2023, the regimen should be considered the new standard of care for this patient population. To know more about metastatic prostate cancer treatment guidelines, visit @ Metastatic Prostate Cancer Management Metastatic Prostate Cancer Pipeline Therapies and Key Companies Capivasertib (AZD 5363): AstraZeneca Bavdegalutamide (ARV-110): Arvinas MVI-816 (pTVG-HP): Madison Vaccines PT-112: Phosplatin Therapeutics HC-1119: Hinova Pharmaceuticals OPDIVO (nivolumab): Bristol Myers Squibb KEYTRUDA (Pembrolizumab/MK-3475): Merck MGC018 (vobramitamab duocarmazine): MacroGenics DS-7300: Daiichi Sankyo Ceralasertib: AstraZeneca Ladiratuzumab vedotin: Seagen/Merck BMS-986218: Bristol-Myers Squibb TAS-115: Taiho Pharmaceutical ModraDoc006/r: Modra Pharmaceuticals Vudalimab: Xencor (Lu-177) - PNT2002: Point Biopharma LNTH-1095 (MIP-1095): Lantheus Holdings ZEN-3694: Zenith Epigenetics EPI-7386: Essa Pharma 177Lu-DOTA-rosopatamab: Telix Pharmaceuticals Proxalutamide: Kintor Pharmaceutical Masitinib: AB Science VERZENIO (Abemaciclib/LY2835219): Eli Lilly and Company CABOMETYX (cabozantinib): Exelixis Learn more about the FDA-approved drugs for metastatic prostate cancer @ Drugs for Metastatic Prostate Cancer Treatment Metastatic Prostate Cancer Market Dynamics The dynamics of the metastatic prostate cancer are expected to change in the coming years. Before 2010, docetaxel was the primary therapeutic option for metastatic castration-resistant prostate cancer (mCRPC), demonstrating improved overall survival compared to the established standard of care. Its approval in 2004, alongside prednisone, marked a milestone in mCRPC treatment. Following initial docetaxel therapy failure, patients faced a dearth of approved second-line treatments for numerous years. However, recent years have witnessed regulatory approvals of multiple drugs in the United States for mCRPC, transforming the treatment landscape. Notably, medications such as JEVTANA, ZYTIGA, XTANDI, LYNPARZA, TALZENNA, AKEEGA, and several others have gained approval. Of late, significant advancements have emerged in the realm of mCRPC, particularly with PARP inhibitors. AKEEGA from Janssen, TALZENNA jointly developed by Pfizer and Astellas Pharma, and the combination of LYNPARZA by AstraZeneca and Merck garnered approval in 2023, showcasing remarkable progress in this domain. PLUVICTO's approval is a significant leap forward in the management of progressive metastatic castration-resistant prostate cancer, bringing improved survival rates to patients with limited treatment alternatives. The drug witnessed an exceptional and robust initial performance in the US market, exceeding expectations. In numerical terms, the pipeline for metastatic castration-resistant prostate cancer appears robust. Antibody-drug conjugates like MGC018 and DS-7300 have demonstrated promising outcomes in clinical trials among mCRPC patients. Nevertheless, except for Point Biopharma's treatment, the majority of these prospective treatments have yet to commence a Phase III trial. Despite this, Arvinas intends to pursue an expedited approval pathway leveraging its Phase II data for regulatory approval. Scope of the Metastatic Prostate Cancer Market Report Therapeutic Assessment: Metastatic Prostate Cancer current marketed and emerging therapies Metastatic Prostate Cancer Market Dynamics: Key Market Forecast Assumptions of Emerging Metastatic Prostate Cancer Drugs and Market Outlook Competitive Intelligence Analysis: SWOT analysis and Market entry strategies Unmet Needs, KOL's views, Analyst's views, Metastatic Prostate Cancer Market Access and Reimbursement Discover more about metastatic prostate cancer drugs in development @ Metastatic Prostate Cancer Clinical Trials Table of Contents Related Reports Prostate Cancer Epidemiology Forecast Prostate Cancer Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, and prostate cancer epidemiology trends. Metastatic Prostate Cancer Pipeline Metastatic Prostate Cancer Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the 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 – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key metastatic castration-resistant 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 Hormone-Refractory Prostate Cancer Pipeline Metastatic Hormone-Refractory Prostate Cancer Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, including clinical and non-clinical stage products, and the key metastatic hormone-refractory 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. 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] +91-9650213330 Logo: SOURCE DelveInsight Business Research, LLP