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2009年10月12日，CSL Behring公司宣布，美国食品药品管理局(FDA)已批准Berinert作为成人及青少年遗传性血管性水肿(HAE)腹部或面部急性发作的对症治疗药。批准之时，Berinert已成为美国已获准的针对该适应证的一线治疗药。
HAE是一种由C1抑制剂(C1-INH)缺乏所致的遗传疾病。该疾病的遗传方式为常染色体显性遗传。HAE的症状包括面部和腹部发生水肿或肿胀。HAE累及腹部时可出现腹部剧痛、腹泻、恶心以及呕吐等症状，此系肠壁肿胀所致；累及面部时可引起面部疼痛性扭曲及肿胀。
Berinert是一种血浆源性静脉治疗药，通过为C1-INH缺乏患者提供其系统中所缺乏的蛋白，治疗产生HAE症状的基本病因。
FDA批准该药用于治疗HAE是基于一项前瞻性、II/III期、国际、多中心、双盲、安慰剂对照试验的结果，该研究对C1-INH的疗效和安全性进行了探讨。试验纳入了124例HAE中或重度急性腹部或面部发作的患者。在参与者中，接受C1-INH治疗组患者症状缓解的中位时间为30 min，而安慰剂对照组为1.5 h。
临床研究中接受Berinert治疗的患者所报告的最严重不良反应，为HAE相关疼痛的严重程度增加。接受该药治疗后患者最常见(即>4%在接受治疗后出现)的不良反应为头痛、腹痛、恶心、肌肉痉挛、疼痛、腹泻以及呕吐。
Berinert禁用于已发生对C1-INH制剂过敏或重度全身反应的患者。应对患者进行变态反应或超敏反应的早期体征(包括荨麻疹、全身风疹、胸闷、喘鸣、低血压以及过敏反应)监测。若疑似超敏反应，应即刻停止输注Beriner并进行适当治疗。应立即使用肾上腺素治疗急性重度超敏反应。
【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，CSL Behring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 BerinertCSL 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. For more information, including full prescribing |
