强生抗癌药Imbruvica新适应症获FDA批准

强生抗癌药Imbruvica新适应症获FDA批准
作者：tomato来源：生物谷

关键词： 强生 Imbruvica ibrutinib 慢性淋巴细胞白血病 CLL

                               
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2014年2月13日讯 /生物谷BIOON/ --强生（JNJ）和Pharmacyclics公司2月12日宣布，抗癌药Imbruvica（ibrutinib胶囊）获FDA批准，用于既往接受过至少一次治疗的慢性淋巴细胞白血病（CLL）患者的治疗。Imbruvica已于2013年11月获FDA批准，用于既往接受过至少一次来那度胺或其他药物治疗的套细胞淋巴瘤（MCL）患者的治疗。这2个适应症的获批，均基于整体缓解率（ORR）数据，该药对存活或疾病相关症状改善的数据尚未建立。

Imbruvica是首个每日一次、单一制剂、口服布鲁顿酪氨酸激酶（BTK）抑制剂，由强生和Pharmacyclics公司联合开发和商业化。此前，Imbruvica治疗CLL和MCL适应症均已授予优先审查资格，并根据FDA的加速批准程序批准。同时，Imbruvica也是FDA授予突破性疗法认定并获批的首批药物之一。

突破性疗法称号是2012年FDA安全和创新法案中制定的部分内容，目的是帮助加快用于严重致命疾病的潜在新药的开发进度，这些药物的临床前研究就已显示比现有的治疗药物在一项或多项临床指标上具有明显改进。

慢性淋巴细胞白血病（Chronic Lymphocytic Leukemia，CLL）是一种淋巴细胞血液癌症，在美国，CLL是一种罕见病。据估计，每年有1.6万人确诊为CLL，有近4600人不幸死于CLL。

Imbruvica是布鲁顿酪氨酸激酶（BTK）抑制剂，通过阻断BTK抑制肿瘤细胞的复制和转移，从而起到抗癌作用。（生物谷Bioon.com）

英文原文：IMBRUVICA™ (ibrutinib) Now Approved in the U.S. for Patients with Chronic Lymphocytic Leukemia Who Have Received At Least One Prior Therapy

HORSHAM, PA, February 12, 2014 – Janssen Biotech, Inc. [“Janssen”] today announced the U.S. Food and Drug Administration (FDA) has approved IMBRUVICA™ (ibrutinib) capsules for the treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy.[1] IMBRUVICA was first approved in November 2013 for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.[1]Both indications are based on an overall response rate (ORR). An improvement in survival or disease-related symptoms has not been established.[1]

IMBRUVICA is the first once-daily, single-agent, oral Bruton’s tyrosine kinase (BTK) inhibitor for patients with CLL who have received one prior therapy and is being jointly developed and commercialized by Janssen and Pharmacyclics, Inc. Both indications were granted priority review and were approved under the FDA’s accelerated approval program; in addition, IMBRUVICA is one of the first medicines with the FDA’s Breakthrough Therapy Designation to receive U.S. approval.

CLL is a slow-growing blood cancer of white blood cells called lymphocytes, most commonly B cells.[2] CLL is an orphan disease (which is defined as a disease impacting fewer than 200,000 Americans[3]) and is primarily diagnosed in those over 70 years old.[2] In the U.S., an estimated 16,000 people are diagnosed with CLL each year[4] and it is estimated that nearly 4,600 will unfortunately die due to this disease.[5] The U.S. prevalence of CLL is approximately 114,500 people.[6]

“CLL is a challenging disease and many physicians switch their patients from therapy to therapy as their disease relapses. There has been a significant need for new alternatives for these patients,” said John C. Byrd, M.D., director, Division of Hematology, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital & Richard J. Solove Research Institute and lead investigator for pivotal CLL trial PCYC-1102-CA.† “The approval of IMBRUVICA provides a new, once-daily oral therapy option for physicians.”

“The speed at which we were able to bring IMBRUVICA to this point epitomizes the sense of urgency that drives oncology drug developers to bring important new medicines to patients in need,” said Craig Tendler, M.D., vice president, Late-Stage Development and Global Medical Affairs for Oncology, Janssen. “We’re delighted and proud of today’s approval, because it represents our commitment to making a difference for patients. We appreciate the ongoing collaboration between the companies and the FDA, which made this possible.”

IMBRUVICA works by blocking a specific protein called BTK.[1] Non-clinical studies have shown that blocking BTK inhibits the enzyme needed by the cancer to multiply and spread.[1]

IMBRUVICA in CLL
The safety and efficacy of IMBRUVICA in patients with relapsed or refractory CLL were evaluated in an open-label, multi-center Phase 1b/2 trial (PCYC-1102-CA) of 48 patients for a median treatment duration of 15.6 months.[1]IMBRUVICA was administered at 420 mg once daily until disease progression or until no longer tolerated by the patient. The ORR and duration of response (DOR) were evaluated according to a modified version of the International Workshop on CLL (IWCLL) criteria by an Independent Review Committee. ORR was 58.3 percent of patients (95% confidence interval (CI) (%), 43.2, 72.4), all partial responses. None of the patients had a complete response. The DOR ranged from 5.6 to 24.2+ months. The median DOR was not reached.[1]

The Warnings and Precautions for IMBRUVICA include hemorrhage, infections, myelosuppression (reduced ability for the bone marrow to produce blood cells), renal toxicity, second primary malignancies and embryo-fetal toxicity.[1]For more information about Warnings and Precautions, please see page four of this release.

The most common Grade 3 or 4 non-hematological adverse reactions (occurring in five percent or more of patients) were pneumonia (8%), hypertension (8%), atrial fibrillation (6.3%), sinusitis (6%), skin infection (6%), dehydration (6.4%) and musculoskeletal pain (6%). The most commonly occurring side effects (adverse reactions in 20 percent or more of CLL patients in the clinical trial) were thrombocytopenia*, diarrhea (63%), bruising (54%), neutropenia*, anemia*, upper respiratory tract infection (48%), fatigue (31%), musculoskeletal pain (27%), rash (27%), pyrexia (fever, 25%), constipation (23%), peripheral edema (23%), arthralgia (joint pain, 23%), nausea (21%), stomatitis (inflammation in the mouth, 21%), sinusitis (21%) and dizziness (21%).[1] (Note: *Treatment-emergent decreases (all grades) of platelets (71%), neutrophils (54%) and hemoglobin (44%) were based on laboratory measurements per IWCLL criteria and adverse reactions.)

Five patients (10%) discontinued treatment due to adverse reactions in the clinical trial (N=48). These included three patients (6%) with infections and two patients (4%) with subdural hematomas. Adverse reactions leading to dose reduction occurred in 13 percent of patients.[1]

The recommended dose of IMBRUVICA for CLL is 420 mg (three 140 mg capsules) orally once daily.[1]

The IMBRUVICA PCYC-1102-CA CLL study was published online in The New England Journal of Medicine in June 2013.[7]

Janssen and Pharmacyclics are continuing an extensive clinical development program for IMBRUVICA, including Phase 3 study commitments in multiple patient populations.

(责任编辑：lishuheng)