Iclusig（ponatinib多激酶抑制剂）比规定时间提前3个月获批
ICLUSIG 15MG TABLET 60/EA
(PONATINIB
ICLUSIG 45MG TABLET 30/EA
(PONATINIB)
美国食品和药物管理局（FDA）14日批准Iclusig（ponatinib多激酶抑制剂）治疗成人两种罕见的血液和骨髓疾病-慢性髓性白血病（CML）和费城染色体阳性急性淋巴细胞白血病（Ph + ALL）。
Iclusig获批比机构排定该产品审查的处方药用户收费规定日期2013年3月27日提前3个月。FDA通过优先审批程序完成了对Iclusig的审查。
Iclusig可阻止促进癌细胞发展的某些蛋白质。该药物日服一次，用于慢性、加速和急变期对酪氨酸激酶抑制剂（TKIs）耐药或不能耐受的CML和Ph + ALL患者的治疗。Iclusig靶向特定基因T315I突变的CML细胞，这种细胞对已获批的酪氨酸激酶抑制剂耐药。
“批准Iclusig非常重要，因为它为对其它治疗药物产生耐药的CML患者尤其是T315I突变型CML患者,提供了一种治疗选择”FDA药品评价和研究中心血液和肿瘤学产品办公室主任、医学博士Richard Pazdur说，“Iclusig是今年获批用于治疗慢性粒细胞白血病的第三种药物以及治疗费城染色体阳性急性淋巴细胞白血病的第二种药物，证明了FDA为罕见疾病患者批准安全有效药物的承诺。”
FDA于2012年9月批准了Bosulif（bosutinib）、2012年10月批准Synribo（omacetaxine mepesuccinate）治疗各阶段CML,2012年8月批准Marqibo（硫酸长春新碱脂质体注射液）治疗Ph + ALL。
有前途的新药物，而该公司进行更多的研究，以确定该药物的临床效益和安全使用。因Iclusig用于治疗罕见疾病药物，它被授予孤儿药称号。
在一个包括有449例不同阶段的CML和Ph + ALL患者的单一临床试验中，对Iclusig的安全性和有效性进行了评估。所有参与试验者均接受Iclusig治疗。
大多数CML患者的费城染色体基因突变细胞表达-主要细胞遗传学反应（MCyR）的百分比下降证明了Iclusig的有效性。54％的患者和70％的T315I突变患者实现了MCyR。MCyR的中位持续时间未达到分析时间。
在CML和Ph + ALL加速、急变期，测定白血细胞计数正常或无白血病症状（主要血液学反应MAHR）的患者数量以证明Iclusig的有效性。结果表明：
·52％的加速期CML患者的MAHR中位持续时间为9.5个月;
·31％的急变期CML患者的MAHR中位持续时间为4.7个月;
·41 percent of patients with Ph+ ALL achieved MaHR for a median duration of 3.2 months. 41％的患者的Ph + ALL聘礼的平均持续时间为3.2个月实现。
批准的Iclusig附带有黑框警告，提醒患者和卫生保健专业人士该药可引起血液凝块和肝毒性。临床试验中报告的最常见的副作用包括：高血压、皮疹、腹痛、疲劳、头痛、皮肤干燥、便秘、发热、关节痛和恶心等症状。
ARIAD Announces Accelerated Approval by FDA of Iclusig (Ponatinib) for Patients with CML and Ph+ ALL Resistant or Intolerant to Prior Tyrosine
Kinase Inhibitor Therapy
The Iclusig bottle (Photo: Business Wire)
~Approved for All Phases of CML
~Product Expected to be Available to Patients Within Approximately Two
Weeks
~Conference Call Scheduled Today at 1:30 p.m. ET ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced that following a priority review, the U.S. Food and Drug Administration (FDA) has granted accelerated approval of Iclusig(ponatinib) for the treatment of adult
patients with chronic, accelerated or blast phase chronic myeloid leukemia(CML) that is resistant or intolerant to prior tyrosine kinase inhibitor (TKI) therapy or Philadelphia chromosome-positive acute lymphoblastic
leukemia (Ph+ ALL) that is resistant or intolerant to prior TKI therapy.
“Today’s FDA approval of Iclusig is an important advance in the treatment of patients with CML and Ph+ ALL who are resistant or intolerant to prior TKI therapy,” stated Harvey J. Berger, M.D., chairman and chief executive officer of ARIAD. “Within less than five years, we were able to bring Iclusig from the start of clinical development to U.S. approval, achieving a major milestone in ARIAD’s history. We have now transformed ARIAD into a commercial oncology company addressing major unmet medical needs for cancer patients.”
Approximately 5,000 new cases of CML are diagnosed each year in the U.S. CML patients treated with TKIs can develop resistance or intolerance over time to these therapies. Iclusig is a targeted cancer medicine discovered and developed at ARIAD. It was designed by ARIAD scientists using ARIAD’s platform of computational chemistry and structure-based drug design to inhibit BCR-ABL, including drug-resistant mutants that arise during treatment. Iclusig is the only TKI that demonstrates activity against the T315I gatekeeper mutation of BCR-ABL, the most common mutation occurring in approximately ten percent of patients with drug resistance.
“The availability of Iclusig will improve the outcome of many patients
with CML and Philadelphia-positive ALL who are resistant or intolerant to prior TKI therapy. It is an effective therapy that meets an unmet medical need and has to date overcome all known resistant mutations in preclinical studies,” said Jorge Cortes, M.D., professor and deputy chair, Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX. “Clinical responses to Iclusig have been observed in patients regardless of their mutation status or stage of disease. It is a valuable new treatment option for leukemia patients.”
“For patients with CML and Philadelphia-positive ALL who become resistant or intolerant to TKI treatments, the approval of Iclusig is very positive news,” said Rosalie Canosa, program division director at CancerCare. “The addition of Iclusig to the arsenal of anti-leukemia medicines is a significant development and one that offers hope for patients coping with CML and Philadelphia-positive ALL.”
The FDA approval of Iclusig was based on results from the pivotal Phase 2 PACE (Ponatinib Ph+ ALL and CML Evaluation) trial in patients with CML or Ph+ ALL who were resistant or intolerant to prior TKI therapy, or who had the T315I mutation of BCR-ABL. Iclusig had robust anti-leukemic activity, with 54 percent of chronic-phase CML patients, including 70 percent of patients with the T315I mutation, achieving a major cytogenetic response(MCyR) – the primary endpoint of the PACE trial for chronic-phase patients.
In patients with advanced disease, 52 percent of accelerated-phase CML
patients, 31 percent of blast-phase CML patients and 41 percent of Ph+ ALL patients achieved a major hematologic response (MaHR) to Iclusig. MaHR was the primary endpoint in the trial for patients with advanced disease.
ARIAD PASS™ Patient Access and Support Services Iclusig will be available to patients in the United States within approximately two weeks through a number of select specialty pharmacies.
The Company has established the ARIAD PASS(Patient Access and Support
Services) program, a comprehensive support system designed to help patients access, afford and adhere to treatment with Iclusig, including
patients without insurance or who are underinsured. ARIAD PASS offers
coverage support, including benefits verification and financial assistance through dedicated benefits coordinators. The program also includes ARIAD PASS Nurses who provide treatment support for patients taking Iclusig.
Healthcare professionals or patients can access information about ARIAD
PASS by calling 1-855-447-PASS (855-447-7277) or visiting www.ARIADPASS.com.
Today’s Conference Call ARIAD will hold a conference call and webcast today, December 14, at 1:30
p.m. ET to discuss the FDA approval of Iclusig, its availability, reimbursement and patient assistance program. The live webcast can be accessed by visiting the investor relations section of the Company’s
website at http://investor.ariad.com. The call can be accessed by dialing 866-831-5605 (domestic) or 617-213-8851 (international) five minutes prior to the start time and providing the pass code 51636171. A replay of the
call will be available on the ARIAD website approximately two hours after
completion of the call and will be archived for three weeks.
About Iclusig (ponatinib) Iclusig is a kinase inhibitor. The primary target for Iclusig is BCR-ABL, an abnormal tyrosine kinase that is expressed in chronic myeloid leukemia (CML) and Philadelphia-chromosome positive acute lymphoblastic leukemia(Ph+ ALL). Iclusig was designed using ARIAD’s computational and structure-based drug design platform specifically to inhibit the activity of BCR-ABL.
Iclusig targets not only native BCR-ABL but also its isoforms that carry mutations that confer resistance to treatment, including the T315I mutation, which is the most common mutation among resistant patients. Iclusig is the only TKI that is effective in CML and Ph+ ALL
patients with this mutation.
Please see important safety information below, and the full prescribing
information for Iclusig at www.ariad.com or www.iclusig.com.
Indication, Usage and Dosing
Iclusig is indicated for the treatment of adult patients with chronic
phase, accelerated phase, or blast phase chronic myeloid leukemia (CML)
that is resistant or intolerant to prior tyrosine kinase inhibitor (TKI) therapy or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) that is resistant or intolerant to prior TKI therapy.
This indication is based upon response rate. There are no trials verifying an improvement in disease-related symptoms or increased survival with Iclusig.
The recommended dose of Iclusig is a 45 mg tablet taken once-daily with or without food.
Important Safety Information Cardiovascular, cerebrovascular, and peripheral vascular thrombosis, including fatal myocardial infarction and stroke have occurred in Iclusig-treated patients. Serious arterial thrombosis occurred in 8% of Iclusig-treated patients. Interrupt and consider discontinuation of Iclusig in patients who develop arterial thrombotic events.
Hepatotoxicity, liver failure and death have occurred in Iclusig-treated patients. Monitor hepatic function prior to and during treatment.
Interrupt and then reduce or discontinue Iclusig for hepatotoxicity.
Warnings and Precautions Twenty patients treated with Iclusig (4%) experienced serious congestive heart failure (CHF) or left ventricular dysfunction, with 4 fatalities.
Monitor patients for signs or symptoms consistent with CHF and treat as
clinically indicated, including interruption of Iclusig. Consider discontinuation of Iclusig in patients who develop serious CHF.
Eight patients treated with Iclusig (2%) experienced treatment-emergent
symptomatic hypertension as a serious adverse reaction, including
hypertensive crisis. Treatment-emergent hypertension occurred in 67% of
patients. Monitor and manage blood pressure elevations.
Clinical pancreatitis occurred in 6% of patients (5% Grade 3) treated with Iclusig. The incidence of treatment emergent lipase elevation was 41%.
Check serum lipase every 2 weeks for the first 2 months and then monthly thereafter or as clinically indicated. Dose interruption or reduction may be required. In cases where lipase elevations are accompanied by abdominal symptoms, interrupt treatment with Iclusig and evaluate patients for pancreatitis.
Serious bleeding events occurred in 5% of patients treated with Iclusig, including fatalities. The incidence was higher in patients with AP-CML, BP-CML, and Ph+ ALL. Most events occurred in patients with grade 4 thrombocytopenia. Interrupt Iclusig for serious or severe hemorrhage.
Serious fluid retention events occurred in 3% of patients treated with
Iclusig. One instance of brain edema was fatal. Monitor patients for fluid retention and manage patients as clinically indicated. Interrupt, reduce, or discontinue Iclusig as clinically indicated.
Symptomatic bradyarrhythmias that led to a requirement for pacemaker
implantation occurred in 3 (1%) Iclusig-treated patients. Advisepatients to report signs and symptoms suggestive of slow heart rate (fainting, dizziness, or chest pain).
Supraventricular tachyarrhythmias occurred in 5% of Iclusig-treated
patients. Atrial fibrillation was the most common supraventricular
tachyarrhythmia. Advise patients to report signs and symptoms of rapid
heart rate (palpitations, dizziness).
Severe (Grade 3 or 4) myelosuppression occurred in 48% of patients treated with Iclusig. Obtain complete blood counts every 2 weeks for the first 3 months and then monthly or as clinically indicated, and adjust the dose as recommended.
Two patients (<1%) treated with Iclusig developed serious tumor lysis
syndrome. Hyperuricemia occurred in 7% of patients. Ensure adequate
hydration and treat high uric acid levels prior to initiating therapy with Iclusig.
Since Iclusig may compromise wound healing, interrupt Iclusig for at least
1 week prior to major surgery. Serious gastrointestinal perforation
(fistula) occurred in one patient 38 days post-cholecystectomy.
Iclusig can cause fetal harm. Advise women to avoid pregnancy while taking Iclusig.
Adverse Reactions
The most common non-hematologic adverse reactions (≥20%) were
hypertension, rash, abdominal pain, fatigue, headache, dry skin, constipation, arthralgia, nausea, and pyrexia. Hematologic adverse reactions included thrombocytopenia, anemia, neutropenia, lymphopenia, and leukopenia. Please see the full Prescribing Information for Iclusig, including the Boxed Warning.
About CML and Ph+ ALL
CML is characterized by an excessive and unregulated production of white blood cells by the bone marrow due to a genetic abnormality that produces the BCR-ABL protein. After a chronic phase of production of too many white blood cells, CML typically evolves to the more aggressive phases referred to as accelerated phase and blast crisis. Ph+ ALL is a subtype of acute lymphoblastic leukemia that carries the Ph+ chromosome that produces BCR-ABL. It has a more aggressive course than CML and is often treated with a combination of chemotherapy and tyrosine kinase inhibitors. The BCR-ABL protein is expressed in both of these diseases.
About ARIAD
ARIAD Pharmaceuticals, Inc. is a global oncology company focused on the
discovery, development and commercialization of medicines to transform the lives of cancer patients. ARIAD’s first medicine, Iclusig™, is approved in the U.S. for the treatment of adult patients with chronic, accelerated or blast phase chronic myeloid leukemia that is resistant or intolerant to prior tyrosine kinase inhibitor (TKI) therapy or Philadelphia chromosome-positive acute lymphoblastic leukemia that is resistant or intolerant to prior TKI therapy. Additional clinical trials of Iclusig in other cancers are ongoing. ARIAD is also studying AP26113, another molecularly targeted medicine, in certain forms of lung cancer. For additional information, visit http://www.ariad.com or follow ARIAD on
Twitter (@ARIADPharm).
This press release contains “forward-looking statements” including, but not limited to, potential regulatory approvals, new indications or labeling for, or potential future sales of Iclusig. Forward-looking
statements are based on management's expectations and are subject to
certain factors, risks and uncertainties that may cause actual results,
outcome of events, timing and performance to differ materially from those expressed or implied by such statements. These risks and uncertainties include, but are not limited to, preclinical data and early-stage clinical data that may not be replicated in later-stage clinical studies, the costs associated with our research, development, manufacturing and other activities, the conduct, timing and results of pre-clinical and clinical studies of our product candidates, the adequacy of our capital resources and the availability of additional funding, and other factors detailed in the Company's public filings with the U.S. Securities and Exchange Commission. The information contained in this press release is believed to be current as of the date of original issue. The Company does not intend to update any of the forward-looking statements after the date of this document to conform these statements to actual results or to changes in the Company's expectations, except as required by law.