2012年12月14日，美国食品药品监督管理局(FDA)批准Ariad制药公司的Iclusig (ponatinib)治疗两种罕见血和骨髓疾病，慢性粒性白血病(CML)和费城染色体阳性的急性淋巴细胞白血病(Ph+ ALL）。
白血病是一类造血干细胞异常的克隆性恶性疾病。其克隆中的白血病细胞失去进一步分化成熟的能力而停滞在细胞发育的不同阶段。在骨髓和其他造血组织中白血病细胞大量增生积聚并浸润其他器官和组织，同时使正常造血受抑制，临床表现为贫血、出血、感染及各器官浸润症状。
Iclusig 是今年底被FDA批准治疗CML的第三个药物和治疗ALL的第二个药物，2012年9月FDA批准Bosulif (bosutinib)和2012年10月批准Synribo (omacetaxine mepesuccinate)治疗慢性粒性白血病。2012年8月批准Marqibo(硫酸长春新碱[vincristine sulfate]脂质体注射液)治疗Philadelphia染色体阴性ALL。
Ponatinib是一种激酶抑制剂,由位于美国麻省剑桥的ARIAD药业开发和生产。美国食品与药品监督管理局要求Ariad公司在药品标签上设置一个称之为“黑盒”的标示，用来警告患者该药有潜在引发动脉血栓及肝毒性的副作用。
Chemical Structure of Iclusig (ponatinib)化学结构
Chemical name for Ponatinib hydrochloride： 3-(imidazo[1,2-b]pyridazin-3ylethynyl)-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide hydrochloride.
CAS Registry Number: 943319-70-8 (Ponatinib , free base), 1114544-31-8 (Ponatinib monohydrochloride), 1232836-25-7 (Ponatinib tris-hydrochloride).
References:
1)Huang, WS; Metcalf, CA; Sundaramoorthi, R; Wang, Y; Zou, D; Thomas, RM; Zhu, X; Cai, L et al. (2010). “Discovery of 3-2-(imidazo1,2-bpyridazin-3-yl)ethynyl-4-methyl-N-{4-(4-methylpiperazin-1-yl)methyl-3-(trifluoromethyl)phenyl}benzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-abelson (BCR-ABL) kinase including the T315I gatekeeper mutant“. Journal of Medical Chemistry 53 (12): 4701–19.
2)O’Hare, T; Shakespeare, WC; Zhu, X; Eide, CA; Rivera, VM; Wang, F; Adrian, LT; Zhou, T et al. (2009). “AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance“. Cancer Cell 16 (5): 401–12.
Ariad’s Iclusig(Ponatinib) Approved to Treat Two Rare Types of Leukemia
The once-daily pill Ponatinib (brand name:Iclusig, previously AP24534) from Ariad Pharmaceuticals was approved by the US FDA on December 14, 2012 to treat two rare types of leukemia (chronic myeloid leukemia and Philadelphia chromosome positive acute lymphoblastic leukemia).
Iclusig blocks certain proteins that promote the development of cancerous cells and treats patients whose leukemia is resistant or intolerant to a class of drugs called tyrosine kinase inhibitors including Bristol-Myers Squibb Co.’s Sprycel and Novartis AG’s Tasigna. Ariad will charge $115,000 a year per patient for Iclusig, a premium over the approximately $100,000 charged by rival drug makers for existing treatments.
The drug will carry a warning on its informational materials, called a black box, about dangers of liver toxicity and arterial thrombosis, or blood clotting.
The FDA said Inclusig is the third drug approved to treat chronic myeloid leukemia (CML) and the second drug approved to treat ALL this year. It approved Bosulif, marketed by Pfizer Inc. (PFE), three months ago and Synribo, marketed by Teva Pharmaceuticals Industries Ltd. (TEVA), in October to treat various phases of CML. Marqibo, marketed by Talon Therapeutics Inc. (TLON), was approved in August to treat Philadelphia chromosome negative ALL
