2014年10月21日讯 /生物谷BIOON/ --强生（JNJ）及合作伙伴Pharmacyclics制药公司近日联合宣布，抗癌药Imbruvica（ibrutinib）获欧盟委员会（EC）批准，用于2种血液癌症：（1）用于复发性或难治性套细胞淋巴瘤（MCL）成人患者的治疗；（2）用于既往接受过至少一种疗法的慢性淋巴细胞白血病（CLL）成人患者的治疗；（3）用于携带del 17p删除突变或TP53突变且不适合化疗-免疫疗法的慢性淋巴细胞白血病（CLL）成人患者的一线治疗。业界此前预计，Imbruvica的年销售额峰值将突破50亿美元。
Imbruvica的获批，是基于在CLL患者中开展的III期RESONATE（PCYC-1112-CA）研究和Ib/II期研究(PCYC-1102)以及在MCL患者中开展的II期研究（PCYC-1104）的积极数据。
套细胞淋巴瘤（MCL）是一种罕见侵袭性B细胞淋巴瘤，该病难以治疗且预后很差。慢性淋巴细胞白血病（CLL）是一种源于骨髓白血细胞（淋巴细胞）的血癌。染色体异常删除突变del 17p和TP53突变与癌症的恶化和耐药性相关，del 17p删除突变是指17号染色体部分片段丢失，携带该突变的CLL患者被认为预后最差。
Imbruvica（ibrutinib）是一种首创的口服布鲁顿酪氨酸激酶（BTK）抑制剂，通过抑制肿瘤细胞复制和转移需要的布鲁顿酪氨酸激酶（BTK）而起到抗癌的作用。BTK是B细胞受体信号复合体中的一种关键信号分子，在恶性B细胞的生存及扩散中起着重要作用。Imbruvica能够阻断介导恶性B细胞不可控地增殖和扩散的信号通路。
FDA分别于2013年12月、2014年2月和2014年7月批准Imbruvica用于经治套细胞淋巴瘤（MCL）、经治慢性淋巴细胞白血病（CLL）、携带del 17p删除突变的CLL的治疗。强生旗下杨森生物科技与Pharmacyclics于2011年12月签署授权协议，联合开发Imbruvica以及该药在美国的商业化，强生拥有Imbruvica在整个EMEA(欧洲、中东和非洲)以及美国以外世界其他地区的商业化权利。
英文原文：Pharmacyclics' (PCYC) IMBRUVICA Approved in Europe for Treatment of Two Blood Cancers
Pharmacyclics, Inc. (NASDAQ: PCYC) today announced that the European Commission (EC) has granted marketing approval for IMBRUVICA® (ibrutinib) throughout the 28 member states of the European Union (EU). IMBRUVICA, a first-in-class, oral, once-daily, non-chemotherapy treatment, now is approved to be marketed in Europe for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL), or adult patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy, or in first line CLL patients in the presence of 17p deletion or TP53 mutation in patients unsuitable for chemotherapy.
IMBRUVICA is being jointly developed and commercialized in the U.S. by Pharmacyclics and Janssen Biotech, Inc. (Janssen). Janssen affiliates will hold the marketing authorization and will market IMBRUVICA in EMEA (Europe, Middle East, Africa), as well as the rest of the world, outside the U.S.
The EC approval was based on data from the Phase II study (PCYC-1104) in MCL, the Phase III RESONATE™ study (PCYC-1112-CA) in CLL and small lymphocytic lymphoma (SLL) and the Phase Ib/II study (PCYC-1102) in CLL/SLL. This approval is based on the IMBRUVICA Marketing Authorization Application (MAA) submitted to the European Medicines Agency (EMA) last year. The EMA is an agency of the EU that administers a centralized procedure for the scientific evaluation of medicines developed by pharmaceutical companies for use in the 28 countries of the EU. In addition to EU markets, a worldwide regulatory filing program for ibrutinib currently is underway.
"We are very pleased that patients with CLL and relapsed or refractory MCL in the European Union will have a first-in-class, oral, single-agent, non-chemotherapy treatment option in IMBRUVICA," said Bob Duggan, Chairman & CEO of Pharmacyclics. "This approval underscores the compelling safety and efficacy benefits of IMBRUVICA, including statistically significant improvement in overall survival and progression-free survival in CLL and the overall robustness of the data in MCL."
IMBRUVICA is approved in the U.S. for three indications: for the treatment of patients with MCL and CLL who have received at least one prior therapy, and for the treatment of CLL patients with deletion of the short arm of chromosome 17 (del 17p), including treatment-naive and previously treated del 17p CLL patients. Accelerated approval was granted for the MCL indication based on overall response rate (ORR). Improvements in survival or disease-related symptoms have not been established in MCL. Continued approval for the MCL indication may be contingent upon verification of clinical benefit in confirmatory trials.
The following results are included in the IMBRUVICA Summary of Product Characteristics (SmPC) from EU commission review.
MCL Study Efficacy ResultsIn a multi-center, single-arm, open-label Phase II study (PCYC 1104), the efficacy of ibrutinib in 111 patients with relapsed or refractory MCL were evaluated. An ORR of 68% was observed, with a complete response rate of 21% and a partial response rate of 47%. With an estimated median follow up of 15.3 months, the estimated median response duration was 17.5 months, and the estimated median progression-free survival (PFS) was 13.9 months.1
CLL Study Efficacy ResultsRESONATE™ (PCYC-1112) is a Phase III, randomized, multi-center, open-label, international, head-to-head study of single-agent, orally-administered ibrutinib versus the intravenously administered monoclonal antibody ofatumumab, targeting the CD-20 antigen. The study enrolled 391 previously treated patients with CLL/SLL.2
At a median follow-up of 9.4 months, single-agent ibrutinib demonstrated a statistically significant improvement in PFS, overall survival (OS), and ORR, regardless of baseline characteristics, as compared with patients treated with ofatumumab.
The PFS results represent a 78% reduction in the risk of progression or death in patients treated with ibrutinib compared to ofatumumab. The OS results represent a 57% reduction in the risk of death in patients receiving ibrutinib versus those in the ofatumumab arm. The efficacy was similar across all of the subgroups examined, including in patients with and without del 17p, a pre-specified stratification factor.
As noted in the market application and reported in The New England Journal of Medicine publication, the RESONATE results were observed despite a total of 57 patients who were initially randomized to ofatumumab crossing over to receive IMBRUVICA prior to the analysis.
MCL and CLL Study Safety ResultsThe most commonly occurring adverse reactions (>20%) were diarrhea, musculoskeletal pain, upper respiratory tract infection, bruising, rash, nausea, pyrexia, neutropenia, and constipation. The most common grade 3/4 reactions (>5%) were anemia, neutropenia, pneumonia, and thrombocytopenia.