Ceplene（组胺双盐酸盐）的新药作为初治药物用于治疗急性髓性白血病（AML）。目前，Ceplene已在欧盟获准销售，用于首次接受治疗的AML患者，作为维持疗法药或防止病情的复发。

中文名称: 组胺二盐酸盐
英文名称: Histamine dihydrochloride
英文同义词: Ceplene;Peremin;OCHLORIDE;HISTAMINE 2HCL;HISTAMINE DIHCL;histaminedichloride;TIMTEC-BB SBB003722;HISTAMINEHYDROCHLORIDE;HISTAMINE DICHLORHYDRATE;bichlorhydrated’histamine
中文同义词: 二盐酸组胺;组胺双盐酸盐;组胺二盐酸盐;二盐酸组织胺;组氨,盐酸盐;组织胺二盐酸盐;組[織]胺鹽酸鹽;HIST胺二盐酸盐;二盐酸组胺, 98+%;二盐酸-Β-氨乙基甘恶啉
CBNumber: CB5183827

欧盟批准二盐酸组胺注射剂上市
欧盟批准EpiCept公司(的二盐酸组胺注射剂（histamine dihydrochloride，Ceplene）上市，用于持续缓解和防止急性髓细胞样白血病（AML）成人患者首次缓解治疗后的复发。本品应与小剂量白介素-2联合用药。本品已获准在欧盟27个成员国以及冰岛、列支敦士登和挪威上市。　　
二盐酸组胺注射剂获准上市是基于其与白介素-2联合用药对320例患者关键的Ⅲ期临床研究结果：完全缓解显著降低了AML患者的复发。接受 Ceplene　/　白介素-2联合用药治疗的患者长期无白血病的比例大于50％。而且，患者对本品耐受性好。　　
二盐酸组胺注射剂是EpiCept公司获准治疗AML的专利，用于防护淋巴细胞免受残留的白血病细胞免疫调节时的破坏。研究表明，本品减少自吞噬细胞产生的氧基、抑制烟酰胺腺嘌呤二核苷磷酸（NADPH氧化酶和防止白介素-2激活NK细胞和T细胞。

Indication

Acute Myeloid Leukemia Remission Maintenance Therapy

Target Population

EU Big 5 34,000 patients
Total EU 47,000 patients

Description

Histamine Dihydrochloride

Dosage and Administration

Ceplene®: 0.5 mg, bid, sub-q Interleukin-2 (Proleukin®): 16,400 IU/kg, bid, sub-q
Treatment comprises 10 cycles
3 cycles comprised of 3 weeks of treatment, followed by 3 weeks of rest
7 cycles comprised of 3 weeks of treatment, followed by 6 weeks of rest

Adverse Reactions

Well tolerated with mild flushing, headache and fatigue
Ceplene® IL-2 self-administered at home

Description

Ceplene® (histamine dihydrochloride), which has received marketing authorization by the European Commission, is administered in conjunction with low dose interleukin-2 (IL-2), for maintenance of first remission in patients with Acute Myeloid Leukemia (AML). AML is the most common type of leukemia in adults. There are approximately 12,000 new cases of AML and 9,000 deaths caused by this cancer each year in the U.S. There are approximately 47,000 AML patients in the EU, with 16,400 new cases occurring each year. There are currently no other effective medical-based remission therapies for AML patients.

AML patients receive intensive induction treatment with chemotherapeutic drugs at diagnosis, and typically become free of detectable leukemia ("complete remission"). However, the majority of patients will experience a relapse of leukemia, usually within one to two years. The survival prognosis after a leukemic relapse is poor. Approximately 75-80 percent of patients who achieve their first complete remission will relapse, and the median time in remission before relapse is only 12 months with current treatments.

Treatment with Ceplene® in conjunction with low dose IL-2 is designed to prevent leukemic relapses in AML patients in remission and prolong leukemia-free survival while maintaining a good quality of life for patients during treatment.

In a Phase III clinical study of 320 patients, Ceplene® met its primary endpoint of increased leukemia-free survival (p <0.01) among AML patients in remission. The results of this trial were published in Blood, a leading scientific journal in hematology, (Blood; The Journal of the American Society of Hematology, volume 108, number 1, pp. 88-96, July 1, 2006).

Stage of Development

The European Commission has approved Ceplene® for the remission maintenance and prevention of relapse in adult patients with Acute Myeloid Leukemia in first remission. Marketing rights have been licensed to Meda AB. In the U.S., Ceplene® is in Phase III.  A pivotal trial to study Ceplene® in AML remission using overall survival as the primary endpoint is expected to commence in 2011. Ceplene® has been granted orphan drug status for the treatment of AML by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA).