Prednisone

点击上方蓝字 关注我们编者按：转移性激素敏感性前列腺癌（mHSPC）作为延缓疾病进展至转移性去势抵抗性前列腺癌（mCRPC）的关键治疗窗口，其治疗策略的优化直接关乎患者长期生存。目前，恩扎卢胺联合雄激素剥夺治疗（ADT）等治疗方案已成为mHSPC的一线选择；近期该联合方案的全球ARCHES研究5年随访结果公布，结果表明该方案进一步为mHSPC患者带来5年长期生存，且无论肿瘤负荷高低均有获益。肿瘤瞭望-泌尿时讯特邀中国人民解放军总医院张旭院士和顾良友教授就相关数据进行深度解读，以期规范我国mHSPC诊疗实践，助力患者实现长期生存。01《肿瘤瞭望-泌尿时讯》mHSPC作为前列腺癌防控的“黄金窗口期”，如何基于肿瘤负荷与患者个体化特征制定治疗策略？顾良友 教授中国人民解放军总医院对于转移性前列腺癌患者而言，激素敏感期无疑是至关重要的治疗阶段；这一时期若能实施及时且有效的治疗策略，往往能使患者获得较长的长期生存时间，显著改善患者预后状况[1]。面对mHSPC患者，2024版《CSCO前列腺癌诊疗指南》推荐进行风险分层[2]。目前而言，临床上主要参考两类分层标准：一是依据肿瘤负荷情况，可分为高瘤负荷和低瘤负荷[CHAARTED标准的高肿瘤负荷定义为≥4处骨转移（含至少一处椎体或骨盆外转移）或内脏转移][3]；二是根据风险程度，分为高风险和低风险[LATITUDE标准则基于高危因素（Gleason评分≥8、≥3处骨转移或内脏转移）][4]。尤其是高风险或高瘤负荷的患者预后相对较差，病情进展速度较快，因此需要充分参考各类临床试验，选择适合的治疗策略，从而针对性改善治疗效果和患者的生存质量。新型内分泌治疗的出现，为转移性前列腺癌的治疗带来了新的曙光。其中，雄激素受体通路抑制剂（ARPI）联合ADT的治疗方案已成为当下的一线治疗标准[2]。目前可供选择的治疗方案众多，不同的治疗组合各有特点：以恩扎卢胺联合ADT为例，该方案经过了长期、多中心的数据验证，能够有效改善患者生存。无论是高瘤负荷还是低瘤负荷的患者，恩扎卢胺方案均能实现全覆盖，为患者提供了有效的治疗选择。值得一提的是，在今年的美国临床肿瘤学会（ASCO）大会上，该方案的最新生存结果得以更新，进一步证实了其在临床上的应用价值。基于这些循证依据，恩扎卢胺治疗方案也获得2024版CSCO前列腺癌诊疗指南、2024版中国泌尿外科和男科疾病诊断治疗指南-前列腺癌诊疗指南、2025版欧洲泌尿外科学会（EAU）指南、2025版美国国家综合癌症网络（NCCN）指南等多项权威指南的认可和推荐，用于一线起始治疗mHSPC“全人群”患者[2,5-7]。在临床实践中，我们也需要根据患者的具体情况，充分考虑患者的个体化特征，进行治疗方案的优化调整。这其中包括多个方面的因素，例如药物可及性与医保纳入情况、患者的经济状况、基础的用药情况（避免药物之间的相互作用对治疗效果产生不良影响；以及不同药物可能引发的严重不良反应等）。02《肿瘤瞭望-泌尿时讯》ARCHES研究5年OS数据出炉，恩扎卢胺治疗持续获益，并可降低30%死亡风险。长期生存获益如何改变中国实践？其亚组分析又带来哪些启示？顾良友 教授中国人民解放军总医院ARCHES研究作为一项全球性、3期、随机、双盲、安慰剂对照研究，为我们提供了极具价值的临床数据。既往总生存（OS）分析结果表明，相较于对照组，恩扎卢胺联合ADT的治疗方案能够降低患者34%的死亡风险（HR 0.66，P＜0.001）[8]。在2025年美国临床肿瘤学会（ASCO）年会上，该研究公布了5年OS随访数据[9]。值得关注的是，在中位随访61.4个月时，尽管ADT联合安慰剂组中有32%（182例）的患者在疾病进展前接受恩扎卢胺的有效治疗，但这一因素并未对整体研究数据产生实质性影响。研究结果显示，恩扎卢胺联合ADT仍较安慰剂联合ADT治疗显著降低患者死亡风险30%（HR 0.70；P=0.0003），恩扎卢胺联合ADT治疗组的患者五年生存率为66%，而安慰剂联合ADT组为53%，充分证明了恩扎卢胺联合ADT治疗方案的有效性。更为值得一提的是，在经过统计学校正交叉因素后，恩扎卢胺联合ADT组的OS获益更加显著，死亡风险降低36%（HR 0.64,95%CI：0.51-0.75）。这一结果进一步强调了恩扎卢胺治疗方案的可靠性和临床应用价值。△ ARCHES研究5年OS分析此外，从临床相关的亚组分析来看[9]，无论是高瘤负荷患者（HR 0.70）还是低瘤负荷患者（HR 0.71），亦或是既往接受过多西他赛治疗的患者（HR 0.67），以及未接受过多西他赛治疗的患者（HR：0.71），各亚组均呈现出阳性结果，即均能从恩扎卢胺治疗方案中获益。这一结果与既往分析结果一致，进一步支持恩扎卢胺联合ADT方案一线治疗mHSPC。△ ARCHES研究5年OS亚组分析03《肿瘤瞭望-泌尿时讯》我们知道ARCHES研究存在交叉（Crossover）队列，那么Crossover设计是否稀释OS获益？您如何看待研究方案的设计，及患者最终获益情况？顾良友 教授中国人民解放军总医院首先，ARCHES研究允许患者进行交叉治疗，这一设计充分体现了以患者为中心的治疗理念，同时也符合临床试验中对伦理和患者获益的高度重视。从此前公布的ARCHES研究4年随访OS分析结果来看，无论是高瘤负荷人群还是低瘤负荷人群，均有部分安慰剂组患者（91/373例 vs 89/203例）交叉进入了试验组。值得注意的是，低瘤负荷人群中接受交叉治疗的患者比例更高（高瘤负荷亚组vs 低瘤负荷亚组=24.4% vs 43.8%）[10]。在未进行校正分析时，低瘤负荷组患者的总生存期已呈现出获益趋势（HR 0.66， 95%CI 0.43-1.03）；而校正交叉治疗的影响后，该亚组存在显著的OS获益（HR 0.56， 95%CI 0.34-0.86）[10]。△ ARCHES研究校正交叉治疗影响后的5年OS亚组分析综上所述，尽管ARCHES研究中存在交叉治疗可能在一定程度上稀释了疗效差异，但恩扎卢胺仍显示出持续的生存优势。这一结果进一步强化了恩扎卢胺作为mHSPC标准治疗的地位，为临床实践提供了坚实的循证医学支持。04《肿瘤瞭望-泌尿时讯》此外，恩扎卢胺也进行了中国人群的China ARCHES研究，结果证实恩扎卢胺联合ADT治疗后76.3%患者可达到PSA不可测（PSA＜0.2ng/ml）应答，且相比安慰剂联合ADT可显著降低PSA进展风险87%。这对于中国的mHSPC临床实践有何影响？顾良友 教授中国人民解放军总医院China-ARCHES是一项在中国开展的多中心、双盲、随机对照3期研究，其聚焦于中国人群，为我们提供了更具针对性的临床数据。研究结果显示[11]，恩扎卢胺治疗组患者的PSA进展风险显著降低了87%（HR 0.130，P＜0.0001），同时能够降低67%的影像学进展风险（HR 0.330，P＜0.001），并降低82.8%的去势抵抗风险（HR 0.172，P＜0.001）。在2024年欧洲肿瘤内科学会（ESMO）大会上，相关研究进一步公布了恩扎卢胺联合ADT治疗中国mHSPC的患者报告结局[12]。研究表明，恩扎卢胺联合ADT方案在确保显著疗效的同时，并未对患者的生活质量造成负面影响。对于需要长期治疗的患者而言，生活质量是重要的考量因素，这一结果为临床实践提供了有力支持。综合China ARCHES研究与全球ARCHES研究的结果，可以发现中国mHSPC患者能够从恩扎卢胺联合ADT方案中获益，生活质量也能得到保障。随着恩扎卢胺联合ADT成为此类患者的一线治疗方案，中国mHSPC患者的总生存有望进一步延长，这也为实现“健康中国2030”目标提供了有力支撑。大咖点评张旭 院士中国人民解放军总医院就我国的前列腺癌临床诊疗现状而言，多数患者初诊时已处于疾病晚期，常伴有明显临床症状且难以实现根治性治疗，因此如何有效缓解症状负担、延缓疾病进展及保障生活质量，已成为医患双方共同关注的核心议题。晚期前列腺癌通常包括mHSPC、非转移性CRPC，以及mCRPC等阶段。其中，mHSPC作为前列腺癌全程管理的战略窗口期，核心目标在于延迟疾病向mCRPC阶段进展，从而改善患者生存预后并维持生活质量。随着多项ARPI药物研究数据的持续更新及指南推荐级别的提升，mHSPC整体治疗格局已发生显著改变。目前多项国内外指南均推荐，mHSPC应采取恩扎卢胺等ARPI联合ADT的一线治疗策略。以多项指南推荐的恩扎卢胺联合ADT方案为例，其循证医学证据在ARCHES研究中得到多次验证：今年公布的5年随访数据显示，相比安慰剂联合ADT，恩扎卢胺联合ADT治疗死亡风险降低30%，证实该方案可为mHSPC全人群提供持续生存获益，且亚组分析证实无论肿瘤负荷高低或是否联合多西他赛化疗，患者均可获得一致的生存获益。这也意味着通过恩扎卢胺联合ADT的治疗，多数mHSPC患者能够获得5年及以上的生存。这一数据不仅刷新了既往疗效数据，更为mHSPC的全程管理树立了新的临床实践标准。张旭 院士解放军总医院泌尿外科医学部主任中国科学院院士中国医学科学院学部委员中华医学会泌尿外科分会候任主任委员北京市医学会泌尿外科分会主任委员中国人体器官捐献管理中心副主任中国抗癌协会腹腔镜与机器人手术分会主任委员全军战创伤重点实验室主任中央保健委员会专家组成员国家高科技研究发展计划及全军重大后勤科研项目首席科学家全军科技领军人才国家杰出青年基金、国家科技进步奖获得者享受国务院特殊津贴我国泌尿外科腹腔镜和机器人技术的奠基人《中华泌尿外科杂志》、《Bladder》和《微创泌尿外科杂志》等学术期刊主编顾良友 教授中国人民解放军总医院泌尿外科医学部副主任医师、副教授、硕士生导师中华医学会泌尿外科分会临床研究办公室秘书 中国抗癌协会整合肿瘤学分会青委会（青年创新联盟）委员中国抗癌协会中西整合肾癌专委会委员中华医学会老年医学分会泌尿肿瘤青年医师联盟成员入选2023年北京市科技新星计划，主持国家自然科学基金等课题5项以第一/通讯作者于STTT、Innovation、Eur Urol、Cancer Treat Rev、J Urol、Commun Biol等发表论文41篇，中科院Top期刊9篇，H指数27研究成果多次入选ASCO、ESMO、EAU、SIU、UAA等国际会议《BMC Urology》、《Frontiers in Oncology》编委 ，《Cancer Letters》、《Surgery》等审稿人获中华医学科技奖一等奖1项，解放军总医院医疗成果一等奖、科技进步二等奖各1项参考文献上下滑动查看更多内容[1]. 中国前列腺癌研究协作组. 前列腺癌药物去势治疗随访管理中国专家共识（2024版）[J]. 中华肿瘤杂志, 2024, 46(4): 285-295.[2]. 中国临床肿瘤学会（CSCO）指南工作委员会.CSCO前列腺癌诊疗指南（2024）.人民卫生出版社[3]. Sweeney CJ, Chen Y-H, Carducci M, et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. 2015;373(8):737-746.[4]. Fizazi K, Tran N P, Fein L, et al. Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial[J]. The Lancet Oncology, 2019, 20(5): 686-700.[5]. 2024版中国泌尿外科和男科疾病诊断治疗指南-前列腺癌诊疗指南.[6]. P. Cornford, D. Tilki , R.C.N. van den Bergh, et al. EAU-EANM-ESTRO-ESUR-ISUP-SIOG guidelines on prostate cancer. 2025. 1-251[7]. Daniel E. Spratt, Sandy Srinivas, Edward M. Schaeffer, et al. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Prostate Cancer Version 2.2025 — April 16, 2025[8]. Armstrong A J, Iguchi T, Azad A A, et al. LBA25 Final overall survival (OS) analysis from ARCHES: A phase III, randomized, double-blind, placebo (PBO)-controlled study of enzalutamide (ENZA)+ androgen deprivation therapy (ADT) in men with metastatic hormone-sensitive prostate cancer (mHSPC)[J]. Annals of Oncology, 2021, 32: S1300-S1301.[9]. Armstrong A J, Petrylak D P, Shore N D, et al. ARCHES: 5-year follow-up overall survival (OS) analysis of enzalutamide (ENZA) plus androgen-deprivation therapy (ADT) in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC)[J]. 2025 ASCO. 5005[10]. Andrew J. Armstrong et al. Overall survival (OS) in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC) treated with enzalutamide (ENZA) + androgen deprivation therapy (ADT) by high or low disease volume and progression to mHSPC (M0 at diagnosis) or de novo mHSPC (M1 at diagnosis): Post hoc analysis of the phase 3 ARCHES trial.. JCO 40, 115-115(2022).[11]. Gongqian Zeng, et al. China ARCHES: A multicenter phase III randomized double-blind placebo (PBO)-controlled efficacy and safety trial of enzalutamide (ENZA) + androgen deprivation therapy (ADT) vs PBO + ADT in Chinese patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC).Annals of Oncology (2023) 34 (suppl_2): S954-S1000.[12]. Ye D, Chang Y, Li Y, et al. 345P Patient-reported outcomes in metastatic hormone-sensitive prostate cancer (mHSPC): Results from the China ARCHES trial[J]. Annals of Oncology, 2024, 35: S1534-S1535.中关村精准医学基金会特别发起“泌尿肿瘤诊疗新进展分享项目”，助力我国泌尿肿瘤规范化发展，最终使广大患者从中获益。特别鸣谢：北京安斯泰来医药有限公司（来源：《肿瘤瞭望-泌尿时讯》编辑部）声 明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

The article analyzes competition in DMD gene therapies, spotlighting FDA approvals, high costs, & strategic positioning of treatments like Givinostat & Elevidys The race to dominate Duchenne therapy is fierce. Givinostat’s oral HDAC edge meets Elevidys’ micro‑dystrophin promise-but sky‑high prices and safety signals may shape future winners.” — DataM Intelligence AUSTIN, TX, UNITED STATES, June 24, 2025 / EINPresswire.com / -- 1. Disease Overview & Molecular Pathogenesis Duchenne Muscular Dystrophy (DMD) is an X-linked recessive neuromuscular disorder resulting from mutations in the dystrophin gene, which encodes a structural protein critical for muscle fiber stability. Mutations lead to absent or non-functional dystrophin, causing muscle cell fragility, progressive myofiber degeneration, and eventual replacement with fibrofatty tissue. Clinical onset typically occurs by age five, with progressive weakness, loss of ambulation in early adolescence, and death in the late teens to early 20s due to respiratory or cardiac failure. 2. Epidemiology & Market Forecasts DMD affects approximately 1 in 3,500 to 5,000 live male births globally. The therapeutics market, valued at around USD 2.1–2.3 billion in 2023–2024, is projected to grow rapidly, potentially reaching USD 7.4–9.9 billion by 2030–2034. Growth is driven by the expansion of exon-skipping therapies, the entry of gene therapy platforms, increasing diagnosis through newborn screening, and the development of oral and mutation-agnostic treatment modalities. Compound annual growth rates (CAGR) are expected to range between 14% and 40%, depending on regulatory approvals and therapeutic uptake. Download CI Sample Report: https://www.datamintelligence.com/strategic-insights/ci/duchenne-muscular-dystrophy-gene-therapy-competitive-edge-insights 3. Current Treatment Paradigms Exon-Skipping Therapies Antisense oligonucleotides (ASOs) are designed to skip specific exons during pre-mRNA splicing to restore the dystrophin reading frame. Approved agents include: - Eteplirsen for exon 51 - Golodirsen and Viltolarsen for exon 53 - Casimersen for exon 45 These therapies target mutation-specific subpopulations and require weekly IV infusions. Functional benefit is often modest, and long-term outcomes remain under evaluation. Steroidal and Non-Steroidal Orals - Vamorolone, a dissociative corticosteroid, offers anti-inflammatory activity with a reduced side effect profile. It is approved for children aged 6 and older, regardless of mutation type. - Givinostat, a histone deacetylase inhibitor (HDACi), represents the first approved non-steroidal agent with disease-modifying properties, showing promise in reducing muscle fibrosis and preserving function. Gene Therapy - Elevidys (delandistrogene moxeparvovec) is the first FDA-approved AAV-based gene therapy for DMD. It delivers a truncated micro-dystrophin gene via a single IV dose, aiming for durable expression. Initially approved for ambulatory children aged 4–5, Elevidys is now expanding to non-ambulatory populations. However, concerns over liver toxicity, patient deaths in trials, and uncertain durability present critical hurdles. 4. Emerging Pipeline Modalities - Next-Gen AAV Gene Therapies: Several candidates, including RGX-202, SGT-003, and GNT0004, are being developed to enhance transduction efficiency, expand age eligibility, and reduce immunogenicity. - CRISPR/Cas Gene Editing: Preclinical programs aim for single-dose, mutation-independent correction of the dystrophin gene, with potential for a curative approach. - Cell-Based Therapies: Agents like CAP-1002, derived from cardiosphere-derived cells, are being evaluated for their anti-inflammatory and regenerative effects. - Adjunctive Agents: Anti-fibrotic and muscle-stabilizing molecules are being developed to complement dystrophin-restoring treatments, particularly in non-ambulatory stages. 5. Market Access & Commercialization Challenges - Cost Barriers: AAV gene therapies are priced in the multi-million-dollar range. For example, Elevidys costs approximately USD 3.2 million per patient, requiring innovative value-based pricing models. - Regulatory Heterogeneity: While accelerated approvals enable early access, global variation in reimbursement policies complicates commercialization, especially in Europe and Asia-Pacific. - Patient Access Gaps: Most therapies target ambulatory children under 5 years old, leaving older or non-ambulatory patients underserved-a significant market expansion opportunity. - Safety and Durability: AAV-based therapies face scrutiny over immune responses, hepatotoxicity, and uncertain long-term benefit, necessitating rigorous post-marketing surveillance and real-world data collection. Book Free CI Consultation Call: https://www.datamintelligence.com/strategic-insights/ci/duchenne-muscular-dystrophy-gene-therapy-competitive-edge-insights 6. Competitive Landscape: Key Companies and Strategies Sarepta Therapeutics - The current market leader, Sarepta offers the most extensive exon-skipping portfolio and the first approved gene therapy (Elevidys). The company is strategically expanding its label to non-ambulatory populations and building a robust global infrastructure for commercial distribution and real-world data capture. Pfizer - Developing an AAV-based gene therapy (PF-06939926), Pfizer is conducting Phase III trials with a broader patient population than Sarepta’s initial cohort. Pfizer leverages its large-scale manufacturing and global commercial footprint to compete in delivery and scalability. Regenxbio - Its RGX-202 program features proprietary vector technology targeting skeletal muscle for enhanced gene transduction. The program is advancing through Phase II/III studies with a focus on increased dystrophin production and improved durability. Solid Biosciences - This company’s SGT-003 therapy uses a muscle-specific promoter to improve gene expression specificity and safety. Its differentiated vector design and targeted delivery approach aim to overcome limitations of first-generation AAV therapies. NS Pharma (Nippon Shinyaku) - NS Pharma has commercialized viltolarsen (exon 53 skipping) and is pushing for regulatory approval in Europe. The company is focusing on deepening its foothold in exon-skipping with region-specific partnerships and accelerated review designations. Santhera Pharmaceuticals / Catalyst Pharmaceuticals - Vamorolone, their non-steroidal anti-inflammatory steroid alternative, addresses all mutation types and offers an improved side effect profile over corticosteroids, positioning it for widespread uptake in early and maintenance stages of DMD. Italfarmaco - Developer of givinostat, Italfarmaco is targeting muscle fibrosis reduction and functional stabilization. Its HDAC inhibition mechanism offers a unique value proposition as an adjunct to exon-skipping or gene therapy. Emerging Genome Editing Startups - Multiple biotech firms are pursuing CRISPR-based and epigenetic editing strategies to develop curative therapies. These programs, still in preclinical stages, aim to correct the underlying mutation at the genomic level, with potential long-term disease reversal. Ask For Customized CI Service As per Your Business Requirement: https://www.datamintelligence.com/strategic-insights/ci/duchenne-muscular-dystrophy-gene-therapy-competitive-edge-insights 7. Strategic Imperatives for Pharma Stakeholders Pipeline Optimization - Pharma firms must prioritize mutation-independent platforms (e.g., gene editing, full-length dystrophin delivery) and invest in strategies that extend eligibility to older, non-ambulatory patients. Developing combination regimens that include anti-fibrotic agents or oral steroids could further differentiate portfolios. Clinical Trial Innovation - Designing biomarker-rich trials that quantify dystrophin levels, muscle strength, and MRI-detected tissue changes will be essential. Adaptive trials and global multi-site platforms can expedite enrollment and regulatory alignment. Market Access Readiness - Early engagement with payers to shape outcomes-based pricing, annuity payment models, and evidence-based value frameworks will be critical for therapies with high upfront costs. Demonstrating reductions in lifetime disease burden, hospitalizations, and caregiver strain will strengthen economic positioning. Safety and Immunogenicity Management - Companies must invest in pre-treatment screening protocols, liver monitoring guidelines, and immunosuppressive strategies to mitigate the risks associated with viral vector delivery. Transparent communication with regulators and stakeholders regarding adverse events will build long-term trust. Integrated Care Strategy - Support services including home infusion options, digital adherence platforms, and tele-neurology networks will be essential for long-term treatment success and patient engagement. Partnerships with neuromuscular centers can serve as launchpads for patient identification and retention. Diagnostics and Early Intervention - Expansion of newborn screening and carrier detection programs will increase early diagnosis and support early therapeutic intervention-vital for maximizing the efficacy of gene therapies and exon-skipping agents. Global Expansion Strategy - Building tiered pricing frameworks, regional licensing partnerships, and local manufacturing strategies will be crucial for entering emerging markets. Pharma players must prepare to balance innovation with affordability to secure broad international adoption. Read Related CI Reports: 1. Alpha 1 Antitrypsin Deficiency | Competitive Intelligence 2. Chronic Spontaneous Urticaria | Competitive Intelligence Sai Kumar DataM Intelligence 4market Research LLP +1 877-441-4866 sai.k@datamintelligence.com Visit us on social media: LinkedIn X Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.