Ariad公司于周三表示，美国食品和药物管理局已同意优先，或6个月，对其实验性白血病药物ponatinib进行审核。
该药物审核截止日期为2013年3月27日。美国食品和药物管理局通常需要10个月的时间来审查药物的应用，但对治疗取得重大进展或治疗短缺的药物要求时限较短。
今年早些时候ponatinib的一项重要试验表明，ponatinib对一半以上的对目前治疗没有反应的患者有效。
Ariad公司正在寻求美国的批准，批准ponatinib药物用于治疗那些对其它药物无反应的慢性粒细胞白血病患者以及费城染色体阳性的急性淋巴细胞性白血病患者。
Pharmacological Class:
Kinase inhibitor.

Active Ingredient(s):
Ponatinib 15mg, 45mg; tabs.

Company
ARIAD Pharmaceuticals, Inc.
Indication(s):
Chronic, accelerated, or blast phase chronic myeloid leukemia (CML) that is resistant or intolerant to prior tyrosine kinase inhibitor (TKI) therapy. Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) that is resistant or intolerant to prior TKI therapy.

Pharmacology:
Ponatinib inhibits the in vitro tyro­sine kinase activity of ABL and T315I mutant ABL with IC50 concentrations of 0.4nM and 2.0nM, respectively. Ponatinib also inhibits the activity of additional kinases with IC50 concentrations between 0.1–20nM, including members of the VEGFR, PDGFR, FGFR, EPH receptors and SRC families of kinases, and KIT, RET, TIE2, and FLT3. Ponatinib inhibited the in vitro viability of cells expressing native or mutant BCR-ABL, including T315I.

Clinical Trials:
The safety and efficacy of Iclusig were eva luated in a single-arm, open-label, multicenter trial. All 449 patients were given a starting dose of 45mg once daily and were assigned to one of six cohorts based on disease phase (chronic phase CML [CP-CML]; accelerated phase CML [AP-CML]; or blast phase CML [BP-CML]/Ph+ ALL), resistance or intolerance (R/I) to prior TKI therapy, and the presence of the T315I mutation.

The primary endpoint in CP-CML was major cy­togenetic response (MCyR), which included complete and partial cytogenetic responses. The primary endpoint in AP-CML, BP-CML, and Ph+ ALL was major hematologic response (MaHR), defined as either a complete hematologic response (CHR) or no evidence of leukemia. At a median follow up time of 10 months, a total of 54% of CP-CML pa­tients, including (49% of R/I + 70% with T315I mutation), achieved MCyR. The median time to MCyR in CP-CML patients was 84 days. In advanced disease, 52% of AP-CML patients, 31% of BP-CML patients and 41% of Ph+ ALL patients achieved MaHR. The median time to MaHR in patients with AP-CML, BP-CML, and Ph+ ALL was 21 days, 29 days, and 20 days, respectively. The median duration of MaHR for patients with AP-CML, BP-CML, and Ph+ ALL was 9.5 months, 4.7 months, and 3.2 months, respectively.

Legal Classification:
Rx

Adults:
Swallow whole. ≥18 years: 45mg once daily. Concomitant strong CYP3A inhibitors: reduce to 30mg once daily. Dose modification for hematologic and non-hematologic toxicity: see full labeling.

Children:
<18 years: not established.

Warnings/Precautions:
Risk of arterial thrombosis; interrupt and consider discontinuing if occurs. Monitor hepatic function prior to and during therapy; interrupt and then reduce or discontinue therapy for hepatotoxicity. Moderate-to-severe hepatic impairment: not recommended. Monitor for CHF, hypertension, fluid retention, cardiac arrhythmias: treat as clinically indicated. Risk of pancreatitis; check serum lipase every 2 weeks for the first 2 months and then monthly thereafter or as clinically indicated. Interrupt therapy for serious or severe hemorrhage. Obtain CBCs every 2 weeks for the first 3 mont