读医学网

安进（Amgen）及其子公司Onyx制药8月4日公布了血癌药物Kyprolis（carfilzomib）的一项III期ASPIRE研究的既定中期分析数据。该项研究是一项国际性随机III期研究，在792例既往接受过1至3种治疗方案但病情复发的多发性骨髓瘤（multiple myeloma，MM）患者中开展，调查了Kyprolis联合Revlimid（lenalidomide，来那度胺）及低剂量地塞米松（dexamethasone）组合疗法（KRd），相对于来那度胺+低剂量地塞米松组合疗法（Rd）的疗效。该项研究的主要终点是无进展生存期（PFS），次要终点包括：总生存期（OS），总缓解率，缓解持续时间，疾病控制率，健康相关生活质量及安全性。

既定中期分析数据表明，与Rd治疗组相比，KRd治疗组无进展生存期（PFS）具有统计学意义的显著改善（PFS：26.3个月 vs 17.6个月，p＜0.0001）。尽管总生存期数据尚未成熟，但KRd治疗组已表现出积极的趋势。该项研究中观察到的安全性与当前Kyprolis的药物标签一致，包括心源性时间的发生率。因不良事件所致的停药在各组相当，该项研究中未发现新的安全性信号。相关数据将提交至即将举行的美国血液学会第56届年会。

根据ASPIRE研究的数据，安进计划于2015年上半年向全球的监管机构提交监管文件。在美国，该研究的数据可能支持将加速批准转变为完全批准，同时扩大Kyprolis当前的适应症。

多发性骨髓瘤（Multiple myeloma，MM）是第二种最常见的血液癌症，是骨髓内浆细胞异常增生的一种恶性肿瘤。由于骨髓中有大量的异常浆细胞增殖，引起溶骨性破坏，又因血清中出现大量的异常单克隆免疫球蛋白，尿中出现本周氏蛋白，引起肾功能的损害，贫血、免疫功能异常。在美国，目前有7万例患者，每年新增2.4万例。在欧洲，约有8.9万例患者，每年新增3.9万例。在全球范围内，有近23万例患者，每年新增11.4万例。

Kyprolis（carfilzomib）注射液于2012年7体液获FDA加速批准，用于既往接受过包括硼替佐米和一种免疫调节剂（IMiD）在内至少2种疗法、但病情在最后一次治疗时或治疗后60天内恶化的多发性骨髓瘤（MM）患者的治疗。该药的获批是基于缓解率。但改善生存及症状等相关临床益处尚未证实。

英文原文：Amgen Announces Phase 3 ASPIRE Trial Of Kyprolis? In Patients With Relapsed Multiple Myeloma Met Primary Endpoint

Kyprolis Helped Patients Live 8.7 Months Longer Without Their Disease Worsening

Results to Form Basis of Regulatory Filings Beginning in 1H 2015

THOUSAND OAKS, Calif. and SOUTH SAN FRANCISCO, Calif., Aug. 4, 2014 /PRNewswire/ -- Amgen (NASDAQ:AMGN) and its subsidiary, Onyx Pharmaceuticals, Inc., today announced that a planned interim analysis demonstrated that the Phase 3 clinical trial ASPIRE (CArfilzomib, Lenalidomide, and DexamethaSone versus Lenalidomide and Dexamethasone for the treatment of PatIents with Relapsed Multiple MyEloma) met its primary endpoint of progression-free survival (PFS). Patients treated with Kyprolis? (carfilzomib) for Injection in combination with Revlimid? (lenalidomide) and low-dose dexamethasone (KRd) lived significantly longer without their disease worsening (median 26.3 months) compared to patients treated with Revlimid and low-dose dexamethasone (Rd) (median 17.6 months) (HR=0.690, 95 percent CI, 0.570, 0.834, p 0.0001). While the data for overall survival, a secondary endpoint, are not yet mature, the analysis showed a trend in favor of KRd that did not reach statistical significance.

The safety profile observed in this study is consistent with the current U.S. Kyprolis label, including the rate of cardiac events. Treatment discontinuation due to adverse events and on-study deaths were comparable between the two arms. No new safety signals were identified.

Results will be submitted for presentation at the upcoming 56th Annual Meeting of the American Society of Hematology later this year.

We are excited about these clinical results and the positive prospects they suggest for patients with multiple myeloma, said Robert A. Bradway, chairman and chief executive officer of Amgen, adding, Our mission at Amgen is to serve patients by advancing medicines that address serious disease. Kyprolis is an important building block in our robust, differentiated pipeline.

Bradway further explained, Coupled with our recent U.S. regulatory submissions for ivabradine and talimogene laherparepvec and our upcoming regulatory submissions for evolocumab and blinatumomab, our pipeline continues to show notable progress.

Results from the ASPIRE study will form the basis for regulatory submissions throughout the world beginning in the first half of 2015. In the U.S., the data may support the conversion of accelerated approval to full approval and expand the current indication.

In the treatment of patients with multiple myeloma, periods of remission become shorter following each treatment regimen, underscoring the need for new options.  The results of the ASPIRE study demonstrate that Kyprolis can significantly extend the time patients live without their disease progressing, said Pablo J. Cagnoni, M.D., president, Onyx Pharmaceuticals, Inc. The ability of novel therapies to produce deep and durable responses may, one day, transform this uniformly fatal disease to one that is chronic and manageable.

Onyx conducted the ASPIRE study under a Special Protocol Assessment (SPA) from the U.S. Food and Drug Administration (FDA) and has received Scientific Advice from the European Medicines Agency (EMA) on the design and planned analysis of the study.

About ASPIRE

The international, randomized Phase 3 ASPIRE (CArfilzomib, Lenalidomide, and DexamethaSone versus Lenalidomide and Dexamethasone for the treatment of PatIents with Relapsed Multiple MyEloma) trial evaluated Kyprolis in combination with lenalidomide and low-dose dexamethasone, versus lenalidomide and low-dose dexamethasone alone, in patients with relapsed multiple myeloma following treatment with one to three prior regimens. The primary endpoint of the trial was progression-free survival, defined as the time from treatment initiation to disease progression or death. Secondary endpoints included overall survival, overall response rate, duration of response, disease control rate, health-related quality of life, and safety. Patients were randomized to receive Kyprolis (20mg/m2 on days 1 and 2 of cycle 1 only, then 27mg/m2 subsequently), in addition to a standard dosing schedule of lenalidomide (25mg per day for 21 days on, 7 days off) and low-dose dexamethasone (40mg per week in 4 week cycles), versus lenalidomide and low-dose dexamethasone alone. The study randomized 792 patients at sites in North America, Europe, and Israel.

About Multiple Myeloma

Multiple myeloma is the second most common hematologic cancer and results from an abnormality of plasma cells, usually in the bone marrow. In the U.S., approximately 70,000 people are living with multiple myeloma and approximately 24,000 new cases are diagnosed annually.Worldwide, nearly 230,000 people are living with multiple myeloma and approximately 114,000 new cases are diagnosed annually. In Europe, approximately 89,000 people are living with multiple myeloma, and approximately 39,000 new cases are diagnosed annually.

About Kyprolis? (carfilzomib) for Injection

On July 20, 2012, the FDA granted accelerated approval of Kyprolis? (carfilzomib) for Injection for the treatment of patients with multiple myeloma who have received at least two prior therapies including bortezomib and an immunomodulatory agent (IMiD), and have demonstrated disease progression on or within 60 days of completion of the last therapy. Approval was based on response rate. Clinical benefit, such as improvement in survival or symptoms, has not been verified.

Kyprolis is marketed in the U.S. by Onyx Pharmaceuticals, Inc., an Amgen subsidiary.