Ibrutinib获准用于治疗套细胞淋巴瘤

11月13日美国食品药品管理局(FDA)宣布批准Ibrutinib用于治疗既往曾接受过至少1种治疗的套细胞淋巴瘤患者。

套细胞淋巴瘤(MCL)为“孤儿病”，每年诊断的新MCL病例仅为2900例。在美国，MCL仅占所有非霍奇金淋巴瘤病例的6%。

Ibrutinib通过阻断Bruton酪氨酸激酶发挥作用，后者是被非临床研究发现可抑制恶性B细胞生存的B细胞受体信号通路的介质。商品名为Imbruvica的每日1次口服药物Ibrutinib是在突破性疗法认定下获得FDA批准的第二种药物，突破性疗法认定通道的建立是为了加快开发和审查严重或危及生命的疾病的疗法。Ibrutinib是获批用于治疗MCL的第三种药物。

Ibrutinib是在2013年6月递交新药申请4个多月后获得批准，获批的基础是一项II期研究的结果。在该研究中，研究者使用ibrutinib日剂量560 mg治疗111例既往接受过3种(中位数)治疗的复发性或难治性MCL患者，观察到的总缓解率为66%。缓解的中位持续时间为17.5个月。未观察到生存和疾病相关症状方面的改善。

在关键MCL试验中，在接受ibrutinib单药治疗的患者中，最常见的治疗相关不良事件是轻度或中度腹泻、疲劳和恶心(N. Engl. J. Med. 2013;369:507-16)。3级或3级以上血液学事件为中性粒细胞减少(16%)、 血小板减少(11%)和贫血(10%)。

由于ibrutinib显示出显著改善严重疾病的治疗的安全性或有效性的潜力，并且其开发目的是用于治疗罕见病，因此FDA还授予该药优先审查和孤儿产品认定。FDA药物评价和研究中心的血液学和肿瘤学产品主任Richard Pazdur医生表示，Imbruvica获批反映了FDA为罕见病患者提供治疗的承诺。

Ibrutinib由Janssen Biotech和Pharmacyclics公司联合经销。预期这两家公司将继续对ibrutinib开展III期研究，目前两家公司也已向FDA递交申请，希望批准该药用于治疗既往治疗过的慢性淋巴细胞性白血病/小淋巴细胞性淋巴瘤。

爱思唯尔版权所有  未经授权请勿转载

By: PATRICE WENDLING, Internal Medicine News Digital Network

Ibrutinib is now approved for the treatment of patients with mantle cell lymphoma who have received at least one prior therapy, the Food and Drug Administration announced Nov. 13.

The once-daily, oral therapy, marketed as Imbruvica, is the second drug to receive FDA approval under the breakthrough therapy designation established to speed the development and review of treatments for serious or life-threatening diseases.

"Imbruvica’s approval demonstrates the FDA’s commitment to making treatments available to patients with rare diseases," Dr. Richard Pazdur, director of hematology and oncology products in the FDA’s Center for Drug Evaluation and Research, said in a statement.
 
Mantle cell lymphoma is an orphan disease, with only about 2,900 new cases of MCL diagnosed each year. MCL comprises only about 6% of all non-Hodgkin’s lymphoma cases in the United States.

Ibrutinib’s approval comes a little more than 4 months after the new drug application was filed in June 2013 and is based on a phase II study reporting an investigator-assessed overall response rate of 66% at a daily dose of 560 mg ibrutinib in 111 patients with relapsed or refractory MCL after a median of three prior therapies. The median duration of response was 17.5 months. An improvement in survival and disease-related symptoms has not been established.

Ibrutinib works by blocking Bruton’s tyrosine kinase, a mediator of the B-cell receptor signaling pathway that has been shown in nonclinical studies to inhibit malignant B-cell survival.

The FDA also granted ibrutinib priority review and orphan-product designation, because the drug demonstrated "the potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition and is intended to treat a rare disease," according to the FDA statement.

Ibrutinib is the third drug approved to treat MCL. In June 2013, the FDA approved the oral thalidomide analogue lenalidomide (Revlimid) for the treatment of MCL that had relapsed or progressed after two prior therapies including bortezomib (Velcade), a subcutaneous therapy that has been available for MCL since 2006.

"It is gratifying to see an early example of the new breakthrough therapy designation pathway meeting its intention – getting promising treatments to patients who are waiting for new options," Dr. Ellen V. Sigal, chairperson and founder of the Washington-based Friends of Cancer Research advocacy organization, said in a statement issued by Janssen Biotech, which is comarketing the drug with Pharmacyclics.

The two companies are expected to continue with phase III studies of ibrutinib and have also submitted the drug to the FDA for the treatment of previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma.

In the pivotal MCL trial, the most common treatment-related adverse events with single-agent ibrutinib were mild or moderate diarrhea, fatigue, and nausea (N. Engl. J. Med. 2013;369:507-16). Grade 3 or higher hematologic events were neutropenia (16%), thrombocytopenia (11%), and anemia (10%).