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[2]。
强生公司今日宣布，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[1]，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）[3]。
泽倍珂®是BRCA1/2突变mCRPC成人患者的一线靶向治疗方案[4]。作为一种高选择性聚腺苷二磷酸核糖聚合酶(PARP)抑制剂[5]，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[3],[6],[7]。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[8]。
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[9]。尽管随着我国医疗水平的提高，前列腺癌的治疗已经取得一定进展，但是mCRPC仍然是一种致命的疾病[10],[11]。据统计，大约10-15%的mCRPC患者携带BRCA1/2基因突变[12],[13]，而携带BRCA1/2基因突变的前列腺癌往往恶性程度更高，可能具有更强的侵袭性和更高的转移性疾病比例，患者的生存结局更差[14],[15],[16],[17],[18]。因此，NCCN和EAU等国内外权威指南均推荐对mCRPC患者进行基因检测，以提供更加精准的治疗决策，改善患者临床获益[19],[20]。
强生创新制药中国区总裁Cherry Huang女士表示："泽倍珂®的获批再次印证了前列腺癌精准治疗时代的到来，突显了基因检测在前列腺癌诊疗中的重要意义。长期以来，强生始终关注不同疾病阶段前列腺癌患者的切实需求，持续引入创新疗法及产品组合，从前列腺癌的晚期治疗，进一步覆盖到更早期阶段。同时，我们也希望让更多患者实现前列腺癌全程管理，在早期、规范化、足疗程的诊疗中获得更长生存。"
此次泽倍珂®的获批是基于一项随机、双盲、安慰剂对照的多中心III期MAGNITUDE研究。结果显示，在BRCA突变亚组中，尼拉帕利联合醋酸阿比特龙加泼尼松或泼尼松龙（AAP）显著降低影像学进展或死亡风险达47%（rPFS, HR=0.53；95%CI 0.36，0.79；p=0.0014）[3]。在第二次期中分析时，中位随访时间为24.8个月，与安慰剂联合AAP的10.9个月相比，尼拉帕利联合AAP治疗BRCA突变亚组的中位rPFS为19.5个月（HR，0.55[95%（CI），0.39-0.78]）[21]。此外，尼拉帕利在至症状进展时间（TSP）上有统计学意义上的获益，与对照组相比，症状进展风险显著降低了46%（未达到中位数与23.6个月相比；HR=0.54，95% CI：0.35-0.85；P=0.0071）[3]。值得注意的是，试验还观察到，接受尼拉帕利联合APP治疗的BRCA1/2 基因突变 mCRPC 患者与接受安慰剂联合AAP治疗的患者相比，尼拉帕利在至细胞毒性化疗起始时间（TCC）上达到统计学意义和临床意义的改善（中位时间未达到 vs. 27.3 个月；HR：0.56，95% CI：0.35-0.90； p=0.0152）[3]。
在安全性方面，研究显示尼拉帕利和AAP联合用药与单药的已知安全性一致。该联合疗法最常见的不良反应（＞10%）包括肌肉骨骼疼痛、疲乏、便秘、高血压、恶心、水肿、呼吸困难等[3]。
[1] 强生公司基于《化学药品注册分类及申报资料要求》中2类（2.3）改良型新药新复方制剂的类别递交申请并获得了审批。2类：境内外均未上市的改良型新药。指在已知活性成份的基础上，对其结构、剂型、处方工艺、给药途径、适应症等进行优化，且具有明显临床优势的药品。2.3含有已知活性成份的新复方制剂，且具有明显临床优势。
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[3] AKEEGA® China Prescribing Information, August 2024
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[6] Clinicaltrials.gov. A Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for the Treatment of Participants With Deleterious Germline or Somatic Homologous Recombination Repair (HRR) Gene-Mutated Metastatic Castration Sensitive Prostate Cancer (mCSPC) (AMPLITUDE). Available at: https://clinicaltrials.gov/ct2/show/NCT04497844. Last accessed: April 2023.
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[20] EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer 2023.
[21] Eleni Efstathiou, et al. 2023ASCO GU abstract 170.