拜耳（Bayer）2月18日公布了III期研究PROTECT VIII的积极数据。该项研究调查了实验性长效、位点特异性聚乙二醇化重组人凝血因子VIII（PEG-rFVIII）复合物BAY94-9027用于治疗A型血友病的疗效和安全性。数据表明，该项研究达到了主要终点。
该项研究中，当每7天1次、每5天1次、每周2次预防性应用BAY94-9027时，可提供出血保护。此外，应用1次或2次输注，可有效解决91%的急性或突破性出血（Breakthrough bleeding，BTB）。该项研究的详细数据将提交至2014年5月在澳大利亚墨尔本举行的世界血友病联盟会议（WFHM）。
当前，严重A型血友病的标准治疗是定期预防性输注凝血因子VIII，维持足够高水平的VIII，预防出血。鉴于目前已上市的因子VIII产品半衰期短，预防性治疗可能需要经常治疗，通常为每天治疗。BAY94-9027在特定的位点聚乙二醇化，具有延长的半衰期，同时保留完整的生物活性。
关于
BAY94-9027通过精心设计，在重组人凝血因子VIII蛋白表面插入一个半胱氨酸残基（Cys），并以此作为聚乙二醇（PEG）聚合物的附着位点，来达到延长半衰期的目的，同时保留rFVIII的生物学活性。拜耳计划于2015年下半年在美国、欧洲及其他国家提交BAY94-9027的上市许可申请。
英文原文：
- The PROTECT VIII study met its primary efficacy and safety objectives for the treatment of patients with hemophilia A
- BAY 94-9027 helped protect against bleeds when used prophylactically with infusion intervals up to seven days
WHIPPANY, N.J., Feb. 18, 2014 /PRNewswire/ -- Bayer HealthCare today announced positive results from the PROTECT VIII trial evaluating the company's investigational long-acting site-specific PEGylated recombinant human factor VIII compound BAY 94-9027. The study met its primary objective of protection from bleeds with fewer infusions. In the study, the site-specific PEGylated factor VIII helped protect against bleeds when used prophylactically every seven days, every five days, and twice per week. The compound was also effective for treatment of acute and breakthrough bleeds with 91 percent of events resolving with one or two infusions.
"These results are very encouraging," said Jerry Powell, MD and Director of the Hemophilia Treatment Center at the University of California Davis. "We have found that this investigational site-specific PEGylated factor VIII may help protect patients from bleeds associated with hemophilia A, even when used every seven days. The current standard of treatment requires infusion every two to three days."
"These data suggest that Bayer's site-specific PEGylated factor VIII may provide longer-lasting protection from bleeds," said Pamela Cyrus, MD, Vice President and Head, U.S. Medical Affairs, Bayer HealthCare Pharmaceuticals. "We are hopeful that less frequent infusions will further support patients in adhering to prophylaxis regimens."
The current standard treatment for severe hemophilia A is regularly scheduled prophylactic infusion of factor VIII to keep factor VIII levels high enough to prevent bleeding. Due to the shorter half-life of currently marketed factor VIII products, prophylaxis may require treatment as often as every other day. Bayer's investigational compound is engineered to extend the circulating half-life while preserving full biologic activity through site-specific pegylation. This site-specific pegylation is achieved by inserting a single cysteine (amino acid) on the factor VIII surface, which serves as an attachment site for a polyethylene glycol (PEG) polymer.
Detailed data are scheduled for presentation at the World Federation of Hemophilia Meeting in May 2014 in Melbourne, Australia. Bayer plans to submit marketing authorization applications to regulatory authorities, including in the U.S., in the second half of 2015.
Studies evaluating the safety and efficacy during major surgery and in pediatric patients are ongoing. Bayer is also planning a study in previously untreated patients.
About the PROTECT VIII study and results
PROTECT VIII (PROphylaxis in hemophilia A patienTs via directly pEgylated long-aCTing rFVIII) is a multicenter, multinational, partially randomized, open-label trial with four treatment arms evaluating the safety and efficacy of the site-specific PEGylated factor VIII in previously treated adults and adolescents with severe hemophilia A. 134 patients were treated in the study. Patients selected either on-demand or prophylactic treatment upon enrollment. All patients in the three prophylaxis arms began treatment with the site-specific PEGylated recombinant factor VIII twice per week. After a ten-week period patients experiencing more than one bleed during this assessment period stayed on two infusions per week at a higher dose and all other patients were randomized to either every five- or seven-day treatment for six months. After randomization, patients who assessed their bleeding control as not adequate could leave the assigned treatment regimen and increase their infusion frequency.
88 percent of patients met the pre-defined criterion of bleeding control in the ten-week initial assessment period and qualified for randomization. All patients receiving infusion every five days (n=43) remained in this treatment arm. 44 percent of patients in the every five-day treatment arm experienced no bleeds. A median annualized bleeding rate (ABR) of 1.9 was observed in this treatment arm.
74 percent of the patients receiving infusion every seven days (n=43) remained in their treatment arm. 37 percent experienced no bleeds. A median ABR of 3.9 (including non-completers) was observed in this treatment arm.
The 13 patients who remained in the two times per week treatment arm, because of their high bleeding rate during the assessment period, reduced their median ABR from 17.4 to 4.1. Patients who received on-demand treatment (n=20) had a median ABR of 23.
The safety objectives were also met. Patients were treated for up to 36 weeks; no inhibitors to factor VIII were confirmed. Two drug-related cases of hypersensitivity reactions were reported. One was assessed as serious, but resolved without medical intervention. No other serious drug-related adverse events were reported.
About Hemophilia A
Hemophilia A, also known as factor VIII deficiency or classic hemophilia, is a largely inherited bleeding disorder in which one of the proteins needed to form blood clots in the body is missing or reduced. Hemophilia A, the most common type of hemophilia, is caused by a deficient or defective blood coagulation protein, known as factor VIII. Hemophilia A is characterized by prolonged or spontaneous bleeding, especially into the muscles, joints, or internal organs.
关键词： 拜耳 A型血友病 治疗药 BAY94-9027 III期 研究 终点
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