Octapharma USA Announces FDA Approval of wilate® - the First Replacement Therapy Developed Specifically for von Willebrand Disease


Milestone Marks Swiss Company’s Entrance into the U.S. Blood Coagulation Market

HOBOKEN, NJ (December 7, 2009) – Octapharma USA today announced the U.S. Food and Drug Administration has approved wilate® for the treatment of spontaneous and trauma-induced bleeding episodes in patients with all types of von Willebrand disease (VWD). Wilate® is a newly developed, high-purity, double virus inactivated von Willebrand Factor/Coagulation Factor VIII Concentrate (Human) that demonstrated efficacy for all types of VWD including pediatric patients in four prospective clinical trials utilizing both objective and subjective data.

Wilate® is indicated for the treatment of spontaneous and trauma-induced bleeding episodes in patients with severe VWD as well as patients with mild or moderate VWD in whom the use of desmopressin is known or suspected to be ineffective or contraindicated.(1) Wilate® is the first double virus inactivated VWF/FVIII (von Willebrand Factor / Factor FVIII), high-purity concentrate, utilizing the solvent/detergent (S/D) process and a special terminal dry-heating (TDH) system. The selected purification processes isolates the VWF/FVIII complex under highly protein-protecting conditions, resulting in an approximately 1:1 ratio of VWF:RCo (ristocetin cofactor) and FVIII activities that is similar to normal plasma. No albumin is added as a stabilizer. Wilate® is exclusively derived from large pools of human plasma collected in U.S. FDA approved plasma donation centers.

The FDA approval of wilate® marks the entrance of Octapharma USA into the U.S. bloodcoagulationmarket,withproductavailabilityscheduledforearly2010.Octapharma USA is the rapidly growing U.S. division of Octapharma AG, one of the largest plasma products manufacturers in the world.

VWD is the most common bleeding disorder, which is found in approximately 1% to 2% of the U.S. population, according to the Centers for Disease Control and Prevention.(2) The illness is a result of the body’s inability to make vonWillebrand Factor, the human protein that helps clot blood.

“The FDA approval of wilate® makes this the first and only replacement therapy developed and manufactured specifically for VWD. Its unique viral attenuation steps and it’s close to 1:1 ratio of FVIII and VWF will provide a next generation treatment option for patients with von Willebrand disease,” said Craig Kessler, M.D., Georgetown University Hospital, Professor of Medicine and Pathology and Director of the Division of Coagulation.

Four prospective clinical trials have demonstrated the safety, tolerability and hemostatic efficacy of wilate® in the treatment of acute bleeding episodes and prophylaxis in patients with various types of VWD. Using objective criteria, wilate® was observed in 1,068 bleeding episodes and determined to be successful between 84% and 93% of the time with results varying dependent on patient type.(3)

“Octapharma’s worldwide commitment to coagulation disorders dates back to Octapharma Group’s formation 25 years ago,” said Octapharma USA President Flemming Nielsen. “We are thrilled that U.S. patients will now have access to wilate® following its significant success in Europe as a next generation therapy. Octapharma is committed to providing the U.S. market with life-enhancing therapies.”

Since the mid-1980s, the requirements for the viral safety of plasma preparations have constantly been made increasingly stringent, requiring demonstrated virus elimination/inactivation.(4) (5) Several viral inactivation steps have enhanced the safety of coagulation products, but S/D inactivation is the current gold standard for safety from highly infectious enveloped viruses (6). Octapharma was the first manufacturer to apply the S/D inactivation to a large-scale production of plasma derivatives. The wilate® manufacturing process provides two independent and effective virus inactivation procedures, namely S/D treatment in bulk and TDH treatment of the lyophilized product in final container. In addition, the ion-exchange chromatography step utilized during wilate® manufacturing contributes to the viral safety.

Plasma contains VWF and FVIII at very lowconcentration.Thewilate®manufacturing process is designed to enrich the proportion of VWF/FVIII complex. Accompanying plasma proteins that may give rise to clinical side-effects, as well as proteases that could impair the stability of coagulation factors and degrade their natural structure and functionality, are efficiently removed during production.


Octapharma AG

Headquartered in Lachen, Switzerland, Octapharma is one of the largest plasma products manufacturers in the world and has been committed to patient care and medical innovation for over 25 years. Octapharma’s core business is the development, production and sale of high quality human protein therapies from both human plasma and human cell lines, including immune globulin intravenous (IGIV). In the U.S., Octapharma’s IGIV product, octagam® (immune globulin intravenous [human] 5%), is used to treat disorders of the immune system, and Octapharma’s Albumin (Human) is indicated for the restoration and maintenance of circulating blood volume. Octapharma employs over 3,000 people and has biopharmaceutical experience in 80 countries worldwide, including the United States, where Octapharma USA is headquartered in Hoboken, N.J. Octapharma operates two state-of-the-art production sites licensed by the U.S. Food and Drug Administration, providing the highest level of production flexibility and minimizing product shortages. For more information, please visit www.octapharma.com.


Forward-looking statements

This news release contains forward-looking statements, which include known and unknown risks, uncertainties and other factors not under the company’s control. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments. These factors include results of current or pending research and development activities and actions by the FDA or other regulatory authorities.


References

(1) Mollison.P.L., Engelfriet C.P., Contreras M.: Some unfavourable effects of transfusion; in Klein H.G., Anstee D.J. (eds): Mollison's Blood Transfusion in Clinical Medicine. Blackwell Publishing, 2005, pp 666-700.
(2) Centers for Disease Control and Prevention. Bleeding disorders. Available at www.cdc.gov/ncbddd/hbd/hemophilia.htm. Accessed on November 22, 2009.
(3) Wilate Approved Complete Prescribing Information, December 2009.
(4) Note for guidance on virus validation studies: The design, contribution and interpretation of studies validating the inactivation and removal of viruses CPMP/BWP/268/95 February 1996.
(5) Note for guidance on plasma-derived products CPMP/BWP/269/95, rev.2. July 1998.
(6) Farrugia A . Guide for the assessment of clotting factor concentrates for the treatment of Hemophilia. 2003, WFH.

---Octapharma获得专门针对血管性血友病开发的首款替代疗法(wilate(R)罕见病药物)
    全球最的血浆制品制造商之Octapharma AG 今天宣布，该公司已经获得了美国食品和药物管理局 (FDA) 授予的  wilate(R)  罕见病药物独家授权项授权指定将  wilate(R)  用于重度血管性血友病  (VWD)  患者的自发性或创伤引起的出血治疗，以及某些已知或怀疑对去氨加压素 (desmopressin)  有禁忌或该药物对其无效的轻度和中度  VWD  患者。

    获得了FDA 批准和  wilate(R)  罕见病药物的独家授权标志着 Octapharma  USA  进入了美国凝血市场，产品预定于2010年初上市。业务发展迅猛的  Octapharma  USA  是全球最大的血浆制品制造商之一  Octapharma  AG  旗下的美国分部。

    Octapharma  Group  副总裁  Kim  Bjornstrup  表示：“FDA  授予的  wilate(R)  罕见病药物独家授权是  Octapharma  在开发这款药物中取得的重要成果。要获得罕见病药物的独家授权，需要向  FDA  提交一份关于  wilate(R)  可能较现有疗法具有哪些临床优势的说明  (1)。Wilate(R)  是专门针对血管性血友病的治疗而研发和生产的，包含了两独特的病毒弱化步骤，拥有高纯度以及1:1生理比例的  FVIII（第八因子相关抗原）和VWF（血管性血友病因子），将  VWD  患者提供新一代的治疗方案。”

    wilate(R)  介绍：

    Wilate(R)  是一新开发的高纯度、双重病毒灭活的  VWF/  Coagulation  Factor  VIII  Concentrate（第八凝血因子[人体]浓制剂），展示出了对各类  VWD  患者（包括参与了四项采用客观和主观标准衡量的瞻性临床试验的儿童患者）的治疗效果。

    2009年12月4日，wilate(R)  获得了  FDA  注册，被批准用于治疗重度  VWD  患者的自发性和创伤引起的出血治疗，以及某些已知或怀疑对去氨加压素禁忌或该药物对其无效的轻度和中度  VWD  患者。(2)  wilate(R)  是第一个双重病毒灭活的  VWF/FVIII（血管性血友病因子/  FVIII  因子）高纯度浓制剂，采用了有机溶剂／表面活性剂  (S/D)  工艺和一个特殊的终端干热  (terminal  dry-heating，TDH)  系统。采取的纯化工艺在对蛋白质进行高度保护的条件下将  VWF/FVIII  复合物进行隔离，产生了1:1比例的  VWF:RCo（瑞斯托霉素辅因子）以及类似于正常血浆的  FVIII  活性。Wilate(R)  完全采自美国庞大的人类血浆库。FDA  批准建立了血浆捐赠中心，但制品中没有加入白蛋白作为稳定剂。

    四项前瞻性临床试验已经证明  wilate(R)  在各种  VWD  患者的急性出血和预防治疗中展示出了安全性、耐受性和止血功效。从客观标准来看，wilate(R)  在应用于1068例出血病例中确实取得了84%至93%的成功率，不同患者的治疗结果有所差异。(3)

    自二十世纪80年代中期以来，业界对血浆筹备工作的病毒安全性的要求越来越严格，要求证明病毒已经被清除/灭活(4)  (5)。项病毒灭活步骤的出台提高了凝血制品的安全性，但是  S/D  灭活是当前防止高传染性包膜病毒的黄金安全标准(6)。Octapharma  是全球首家将 S/D 灭活工艺应用于大规模血浆衍生物生产的制造商。wilate(R)  制造工艺提供了两项独立、有效的病毒灭活程序，即用于批量制品的  S/D  处理和对最终容器中冻干产品的  TDH  处理。此外，在  wilate(R)  制备过程中运用到的离子交换台阶色谱法也有助于提高病毒安全性。

    人血浆中含有浓度极低的VWF 和 FVIII.该 wilate(R)制备工艺旨在提高  VWF/FVIII  复合物的比例。同时存在的可能增加临床副作用的血浆蛋白以及可能损害凝血因子稳定性并且降低其自然结构和功能性的蛋白酶，在生产过程中被有效清除。

    血管性血友病介绍：

    血管性血友病  (VWD)  是最常见的出血性疾病，根据美国疾病预防控制中心  (Centers  for  Disease  Control  and  Prevention)  的据，该病在美国人口中的发病率约为1%至2%。(7)  该病是人体无法制造功能性血管性血友病因子导致的结果，人类蛋白可帮助血液凝结。

    Octapharma  Group  简介

    总部位于瑞士Lachen 的Octapharma Group是全球最大的血浆制品制造商之一，过去25年多来一直致力于病患护理和医疗创新。