美国FDA已经批准Berinert（C1酯酶抑制剂[人]，由杰特贝林 ），等离子源的急性腹痛或遗传性血管水肿面部的成人和青少年（栓塞）攻击治疗的C1酯酶抑制剂集中。
The approval was based on results from the Phase 2/3 prospective, double-blind, placebo-controlled International Multi-center Prospective Angioedema C1-Inhibitor Trial (IMPACT), which studied the efficacy and safety of C1-inhibitor (C1-INH) concentrate in 124 HAE patients with acute, moderate, or severe abdominal or facial attacks.该核准是根据从第二阶段的结果/ 3前瞻性，双盲，安慰剂对照的国际多中心前瞻性血管性水肿的C1 -抑制试验（影响），在研究的有效性和安全性的C1抑制剂（的C1 -异烟肼）集中在124例急性动脉栓塞，中度或重度腹部或面部发作患者。 Main study endpoints were time to onset of symptom relief from HAE attacks, proportion of subjects with worsening clinical HAE symptoms, and safety.主要研究终点的时间从栓塞攻击，栓塞的临床症状恶化科目比例，和安全的症状减轻症状。 The study found that C1-INH is effective and safe in rapidly treating acute abdominal and facial skin swellings in adults and adolescents with HAE.这项研究发现的C1 -异烟肼是有效和迅速治疗栓塞成人和青少年急性腹痛和面部皮肤肿胀安全。

The median time to symptom relief was 30 minutes after receiving C1-INH compared with 1.5 hours with a placebo.中位数症状缓解时间为30分钟后接到的C1 -异烟肼与1.5与安慰剂小时。

Berinert will be available in single-use vials containing 500units of lyophilized concentrate. Berinert将在一次性使用小瓶含冻干浓缩500units。

在易致动脉粥样硬化的小鼠使用C1 酯酶抑制剂阻止动脉损伤后的新生内膜形成
背景：尽管在人类动脉粥样硬化（AS）形成中有补体系统的参与，但是在动脉损伤后的重塑过程中补体的作用尚不清楚。我们在ApoE-/-小鼠使用C1-酯酶抑制剂，探讨补体级联对新生内膜形成的影响。
方法和结果：给ApoE-/-小鼠喂饲致AS饮食，并以导丝诱导颈动脉内皮剥脱模型，再于围术期给予C1-酯酶抑制剂（Berinert; 15 IU i.v.）或赋形剂，随之每2天给一次。通过检测血浆C1-酯酶抑制剂活性来证实治疗效果。结果发现在C1-酯酶抑制剂处理的小鼠，血清甘油三酯显著减少，而胆固醇水平无显著改变。三周后，C1-酯酶抑制剂处理小鼠的新生内膜面积显著下降，而中膜面积无显著改变。这些改变与新生内膜、中膜巨噬细胞和CD3+T细胞含量减少有关。RT-PCR检测显示，C1-酯酶抑制剂处理的小鼠损伤后10天的斑块中，C3mRNA表达显著下降；且ELISA法也证实损伤后C3的血清峰值显著下降；免疫化学揭示在斑块的巨噬细胞中C3和C3c共存且有强表达，而在C1-酯酶抑制剂
处理的小鼠则显著下降。在离体流动条件下，C1-酯酶抑制剂削弱单核细胞停顿于激活的内皮和血小板，并在体阻止白细胞向损伤后一天的颈动脉募集。
结论：C1-酯酶抑制剂限制新生内膜形成和炎症反应，这可能与补体的激活、白细胞募集被阻止以及甘油三酯下降有关，从而提供另一种治疗动脉疾病的方法。
      
【题　名】CSL Behring计划申请HAE候选治疗药
【作　者】钱苏宁（摘）
【机　构】不详
【刊　名】国外药讯, 2008(6): 33-34
【关键词】治疗药 HAE 遗传性血管性水肿 候选 Ⅲ期临床试验 欧洲国家 加拿大 抑制剂
【文　摘】在得到Ⅲ期临床试验的正面结果以后，CSLBehring公司计划在美国、加拿大、欧盟申请人C1抑制剂Berinert（Cl-INH）（I）作为治疗遗传性血管性水肿（HAE）的药物。该产品已在包括德国、奥地利、瑞士等国在内的几个欧洲国家上市，并已销售了30年。

FDA Approves Berinert
CSL Behring Announces FDA Approval of Berinert, First and Only Therapy Approved for the Treatment of Acute Abdominal and Facial Attacks of Hereditary Angioedema in U.S.
      
KING OF PRUSSIA, Pa., Oct. 12 /PRNewswire/ -- CSL Behring announced today that the U.S. Food and Drug Administration (FDA) has granted marketing approval for Berinert C1-Esterase Inhibitor, Human for the treatment of acute abdominal or facial attacks of hereditary angioedema (HAE), a rare and serious genetic disorder, in adult and adolescent patients. Berinert
is the first and only therapy approved for this indication in the U.S.
The approval is based on the results of the phase II/III prospective, double-blind placebo-controlled International Multi-center Prospective Angioedema C1-Inhibitor Trial (I.M.P.A.C.T.), which studied the efficacy and safety of C1-inhibitor (C1-INH) concentrate. The safety and efficacy of Berinert for prophylactic therapy have not been established.
      
The FDA approval of Berinert marks an important milestone in CSL Behring's ongoing commitment to satisfying the unmet needs of patients with rare and serious disorders, such as hereditary angioedema," said Robert Lefebvre, Vice President and General Manager of U.S. Commercial Operations at CSL Behring. "As a leader in developing safe, effective and high-quality therapies, we are pleased to add to our rapidly growing portfolio a proven treatment that can make a positive difference in the lives of HAE patients
and their families."
HAE is a genetic disorder caused by a deficiency of C1-INH and is inherited in an autosomal dominant manner. Symptoms of HAE include episodes of edema or swelling in the face and the abdomen. Patients who have abdominal attacks of HAE can experience episodes of severe pain, diarrhea, nausea, and vomiting caused by swelling of the intestinal wall.
HAE attacks that involve the face can cause painful distortion and painful swelling. Diagnosis of HAE requires a blood test to confirm low or abnormal levels of C1-INH.
There are estimates of 6,000 to 10,000 or more people with HAE in the U.S."For individuals with HAE, episodes of swelling can be extremely painful and frightening, " said Timothy Craig, MD, professor of medicine and pediatrics, Pennsylvania State University Hershey Medical Center. "With the approval of Berinert, healthcare professionals can now provide HAE patients in the U.S. with a safe and effective treatment option that  rapidly relieves the symptoms of acute attacks in the face and abdomen."
"Today's approval provides adult and adolescent HAE patients and their physicians with a proven, safe, and effective therapy for treating debilitating, painful, and life-threatening facial and abdominal HAE attacks once they have begun," said Anthony J. Castaldo, President of the United States Hereditary Angioedema Association, a nonprofit patient advocacy organization that represents approximately 6,500 HAE patients in the United States.
About I.M.P.A.C.T.I.M.P.A.C.T. was a study of 124 HAE patients with acute, moderate, or severe abdominal or facial attacks. C1-INH concentrate was administered at two different doses and compared with placebo.
The main study endpoints were time to onset of symptom relief from HAE attacks, proportion of subjects with worsening clinical HAE symptoms, and safety.
The I.M.P.A.C.T. study found that C1-inhibitor concentrate (C1-INH) is effective and safe in rapidly treating acute abdominal and facial skin swellings in adults and adolescents with HAE.
The study found that the median time to symptom relief was 30 minutes after receiving C1-INH compared with 1.5 hours with a placebo.
About BerinertBerinert, a plasma-derived intravenous therapy, treats the fundamental cause of acute facial and abdominal hereditary angioedema (HAE) symptoms by providing C1-INH deficient adult and adolescent patients with the missing human protein. Without C1-INH, patients with HAE suffer from recurrent episodes of rapid swelling of areas of the skin and underlying tissues including the face, mouth and abdomen. Berinert is a unique HAE therapy because of its reliable record of proven efficacy and safety in international clinical use in over 400,000 treatments in Germany, Austria, Switzerland, and several other countries where it is manufactured and sold by CSL Behring under the trade name Berinert P.
Important Safety InformationBerinert is a plasma derived concentrate of C1 Esterase Inhibitor (Human), indicated for the treatment of acute abdominal or facial attacks of hereditary angioedema (HAE) in adult and adolescent patients.
The safety and efficacy of Berinert for prophylactic therapy have not been established. Berinert is contraindicated in individuals who have had an anaphylactic or severe systemic reaction to C1-INH preparations. Monitor patients for early signs of allergic or hypersensitivity reactions (including hives, generalized urticaria, chest tightness, wheezing, hypotension, and anaphylaxis). If hypersensitivity is suspected, immediately discontinue administration and initiate appropriate treatment.
Epinephrine should be immediately available for treatment of acute severe hypersensitivity reactions.
Thrombotic events have occurred in patients receiving off-label high doses of Berinert. Monitor patients with known risk factors for thrombotic events.
Berinert is derived from human plasma. The risk of transmission of infectious agents, including viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent, cannot be completely eliminated.
The most serious adverse reaction reported in subjects in clinical studies who received Berinert is an increase in the severity of pain associated with HAE.
The most common adverse reactions observed in more than 4 percent of subjects after Berinert treatment were headache, abdominal pain, nausea, muscle spasms, pain, diarrhea, and vomiting.Berinert has not been evaluated in pregnant women or nursing mothers; benefits of treatment should be weighed against potential risks in pregnant women, and Berinert should be given to nursing mothers only if clearly needed. Safety and efficacy of Berinert have not been established in children (ages 0 through 12) or in the geriatric population.
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