CSL Behring Receives FDA Approval of HizentraTM, First 20 Percent Subcutaneous Immunoglobulin Therapy New high concentration, at-home therapy offers convenience to patients managing primary immunodeficiency – a rare and serious disorder affecting millions worldwide KING OF PRUSSIA, Pa.--(BUSINESS WIRE)--CSL Behring announced today that the U.S. Food and Drug Administration (FDA) has granted marketing approval for HizentraTM, Immune Globulin Subcutaneous (Human), 20% Liquid, for treating patients diagnosed with primary immunodeficiency (PI). A once weekly immunoglobulin (Ig) replacement therapy, Hizentra provides effective protection against infection by maintaining a steady and normal level of immunoglobulin in the body. Primary immunodeficiencies constitute a group of disorders, usually genetic, that cause a malfunction in all or part of the immune system, thereby rendering the patient unable to fight off infections caused by everyday germs. Hizentra is the first 20 percent subcutaneous immunoglobulin (SCIg) approved in the U.S. by the FDA. This high-concentration product is stabilized with L-proline, a naturally-occurring amino acid. L-proline allows Hizentra to be stored at room temperature (up to 25°C [77°F]). Because no refrigeration is necessary, Hizentra is ready to use, offering patients and physicians convenience and portability. Hizentra can be safely self-administered by PI patients under a physician's care. "As the first SCIg treatment with a 20 percent concentration of immunoglobulin, Hizentra represents an effective, convenient choice of at-home Ig therapy that will allow people with PI to schedule treatment around their busy lives instead of scheduling their lives around treatment,” said Robert Lefebvre, Vice President and General Manager, U.S. Commercial Operations at CSL Behring. “Hizentra is an important new addition to the rapidly growing CSL Behring product portfolio, and further demonstrates our long-standing commitment to the PI and rare disease communities.” "With its high concentration, Hizentra is a welcome new SCIg treatment option for patients managing primary immunodeficiencies,” said John Sleasman, M.D., Professor and Chief of the Division of Allergy, Immunology and Rheumatology at the University of South Florida College of Medicine, Department of Pediatrics, and one of the investigators on CSL Behring's clinical study of Hizentra. "Hizentra’s ready-to-use attribute will allow patients to infuse the product where and when it suits them, and physicians now have another product to select to best meet the individual needs of their patients.” For patients with primary immunodeficiencies, immunoglobulin replacement therapy with a product like Hizentra can help treat existing or chronic infections and prevent new infections from occurring. No single treatment works for every type of PI, but infusions of replacement antibodies (immunoglobulins) can help supplement the immune system to prevent infection in nearly three-quarters of PI cases that are due to antibody deficiencies. Immunoglobulin, or Ig, is a blood component that has become standard immune replacement therapy for most people living with PI, and nearly 70 percent of PI patients receive Ig replacement therapy. Since the 1980s, the first-line therapy for most PI patients has been intravenous immunoglobulin (IVIg), in which immunoglobulin is delivered through a needle into the vein. Many patients, however, cannot easily tolerate intravenous infusions due to serious side effects or poor veins. Hizentra allows patients to use a small, portable pump to self-administer their weekly infusions by injection under the skin (subcutaneous administration). Hizentra is part of CSL Behring’s Ig franchise, which also includes both the first FDA-approved subcutaneous Ig treatment and the first proline-stabilized IVIg therapy. Hizentra, also stabilized with proline, will be manufactured at CSL Behring’s new state-of-the-art facility, located at its center of excellence for immunoglobulins in Bern, Switzerland. This new manufacturing facility, which uses advanced technologies to ensure product safety and steady supply production, represents CSL Behring’s long-term commitment to global Ig markets. Clinical Studies The FDA approval of Hizentra was based on results from a prospective, open-label, multicenter, single-arm, clinical study conducted in the United States, evaluating the efficacy, tolerability, and safety of Hizentra in adult and pediatric subjects with PI. In this study, subjects previously receiving IVIg treatments every three or four weeks were switched to weekly subcutaneous administration of Hizentra for 15 months (a three-month wash-in/wash-out period followed by a 12-month efficacy period). The efficacy of Hizentra was analyzed in 38 subjects who received at least one infusion after the wash-in/wash-out period. Important Safety Information HizentraTM, Immune Globulin Subcutaneous (Human), is indicated for the treatment of patients with primary immunodeficiency (PI). Hizentra is contraindicated in individuals with a history of anaphylactic or severe systemic response to immune globulin preparations or components of Hizentra, and in persons with selective immunoglobulin A deficiency who have known antibody against IgA and a history of hypersensitivity. If anaphylactic reactions are suspected, administration should be discontinued immediately and the patient treated as medically appropriate. Because Hizentra contains the stabilizer L-proline, it is also contraindicated in patients with hyperprolinemia. Hizentra is derived from human plasma. The risk of transmission of infectious agents including viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent, cannot be eliminated completely. The most common drug-related adverse reactions, observed in 5 percent or more of subjects in the clinical study, were local injection-site reactions, headache, vomiting, pain, and fatigue. Monitor patients for reactions associated with IVIg treatment that might occur with Hizentra, including renal dysfunction/failure, thrombotic events, aseptic meningitis syndrome (AMS), hemolysis and transfusion-related acute lung injury (TRALI). For more information, including full prescribing information, visit www.hizentra.com. About Primary Immunodeficiencies Nearly 100 types of PIs exist. For individuals with PI, many of them children, infections may not improve as expected with usual treatments and may keep returning. As a result, patients may face repeated rounds of antibiotics or hospitalization for treatment. Repeated infections can lead to organ damage, which over time can become life-threatening. Some infections, such as meningitis, may even result in death. Collectively, PIs affect an estimated 10 million people worldwide, and the incidence is estimated to be 1 in 10,000. Due to the X-linked inheritance in many PI syndromes, more males are affected than females. For more information on PI, please visit www.cslbehring.com or contact the leading PI patient advocate groups in the U.S., the Immune Deficiency Foundation and the Jeffrey Modell Foundation. About CSL Behring CSL Behring is a leader in the plasma protein therapeutics industry. Committed to saving lives and improving the quality of life for people with rare and serious diseases, the company manufactures and markets a range of plasma-derived and recombinant therapies worldwide. CSL Behring therapies are indicated for the treatment of coagulation disorders including hemophilia and von Willebrand disease, primary immune deficiencies and inherited respiratory disease. The company’s products are also used in cardiac surgery, organ transplantation, burn treatment and to prevent hemolytic diseases in newborns. CSL Behring operates one of the world’s largest plasma collection networks, CSL Plasma. CSL Behring is a subsidiary of CSL Limited (ASX:CSL), a biopharmaceutical company headquartered in Melbourne, Australia. For more information, visit CSL Behring公司2010年3月4日宣布，美国FDA已经批准其20%浓度的皮下注射用免疫球蛋白（Hizentra）用于原发性免疫缺陷患者。 作为一周1次用药的免疫球蛋白替代疗法，本品可使机体免疫球蛋白水平维持在稳定和正常水平，从而有效抵抗感染。 原发性免疫缺陷通常为遗传性疾病，可导致整个或部分免疫系统障碍，从而使患者无法抵抗各种常见病原菌导致的感染。 本品是首个获得美国FDA批准的20%皮下用免疫球蛋白。这种高浓度产品通过天然氨基酸L-脯氨酸来保持稳定。L-脯氨酸使本品能够在室温（不超过25ºC）下保存。由于不需要冰箱保存，本品随时可用，使用方便且易于携带。在医师的指导下，原发性免疫缺陷患者可安全地自我用药。 免疫球蛋白替代治疗药Hizentra获准用于治疗原发性免疫缺陷病 圣路易斯(MD Consult)——2010年3月4日，CSL Behring公司宣布，美国食品药品管理局(FDA)已批准Hizentra用于治疗原发性免疫缺陷病(PI)患者。Hizentra是一种皮下用免疫球蛋白替代治疗药，其市售形式为20%的液体制剂，此浓度高于某些替代药物。对PI患者应用免疫球蛋白替代疗法可能有助于治疗其现有的或慢性感染，并防止发生新的感染。 患者可以使用便携式泵在家自行皮下Hizentra给药。这种人性化制剂可在室温下储存，每周用药一次。 FDA批准Hizentra的依据为一项在美国开展的前瞻性、开放性、多中心、单组临床研究结果，该研究旨在评价Hizentra治疗成人和小儿PI患者的疗效、耐受性以及安全性。在研究中，先前每3周或4周接受1次静脉免疫球蛋白输注治疗的患者换成每周1次Hizentra皮下给药治疗，持续15个月(3个月的洗入或洗脱期后，继以12个月的疗效期)。在38例洗入或洗脱期后接受至少1次输注的患者中分析Hizentra的疗效。 与药物有关的最常见不良反应(即临床研究中所观察到的发生率≥5%)有注射部位局部反应、头痛、呕吐、疼痛以及乏力。 Hizentra禁用于下列人群：对免疫球蛋白制剂或Hizentra成分有过敏反应史或重度全身反应史者；患选择性免疫球蛋白A(IgA)缺陷、已知有针对IgA的抗体及有变态反应史者。若出现疑似Hizentra用药的过敏反应时，应即刻停止输注，并给予患者适当治疗。由于Hizentra含有稳定剂L-脯氨酸，故亦应禁用于患高脯氨酸血症的患者。 Hizentra来源于人血浆。无法完全消除传播病毒等传染源的风险，理论上讲，亦无法完全消除克罗伊茨费尔特-雅各布病的病毒。