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默克脑病药物Kuvan IIIb期研究达主要终点

2014年4月24日讯 /生物谷BIOON/ --默克(Merck KGaA)4月24日宣布,有关药物Kuvan(沙丙蝶呤二盐酸盐)的一项IIIb期SPARK研究达到了主要终点。

SPARK是一项多中心、开放标签、随机、对照IIIb期研究,在此前测试表明对Kuvan治疗有响应、且年龄小于4岁的苯丙酮尿症(PKU)患者中开展,调查了Kuvan的疗效、安全性和群体药代动力学。该研究根据儿科研究方案开展。研究中,患者随机分配至苯丙氨酸限制饮食或Kuvan(10mg/kg/天)+苯丙氨酸限制饮食治疗26周,研究的主要终点是经过26周治疗后,各组对苯丙氨酸的耐受性。次要终点包括研究期间血液中苯丙氨酸含量的变化,各组随着时间腿饮食苯丙氨酸耐受的变化,以及神经功能、生长参数和安全性评估。Kuvan的长期疗效和安全性将在该项研究中为期3年的延长期内进行评估,在延长期内,所有患者均接受Kuvan和苯丙氨酸限制饮食。

SPARK研究数据表明,将Kuvan添加至苯丙氨酸限制饮食,用于4岁以下苯丙酮尿症(PKU)儿童的治疗,可显著提高患者对饮食中苯丙氨酸的耐受性。根据该项研究的积极数据,默克计划今年晚些时候向欧洲药品管理局(EMA)提交Kuvan的标签扩展监管申请。

Kuvan于2008年获欧盟和FDA批准,该药是一种口服制剂,治疗由苯丙酮尿症(PKU)或四氢生物蝶呤(BH4)缺乏症引发的高苯丙氨酸血症(HPA)。Kuvan是首个也是唯一一个与饮食调整相结合的药物,用于降低苯丙酮尿症(PKU)患者血液和大脑中的苯丙氨酸浓度,以防止PKU的破坏性影响。Kuvan适用于所有年龄段的四氢生物蝶呤(BH4)缺乏症患者,以及对Kuvan有响应且年龄大于4岁的PKU患者。

此前,FDA和欧盟均已授予Kuvan孤儿药地位。

默克负责Kuvan在美国、加拿大和日本以外市场的销售,BioMarin负责该药在美国和加拿大的销售,在日本由Asubio制药负责。(生物谷Bioon.com)

英文原文:Merck Announces Positive Outcome of IIIb Study for Kuvan

—Primary endpoint met in SPARK study: significant increase in phenylalanine tolerance demonstrated after 26 weeks of the study in children less than 4 years of age with phenylketonuria and responsive to Kuvan treated with Kuvan plus a phenylalanine-restricted diet, versus diet alone

—SPARK study was conducted as a post-authorization measure and results will be submitted to EMA this year

Darmstadt, Germany, April 24 – Merck, a leading company for innovative and top-quality high-tech products in the pharmaceutical and chemical sectors, announced today that the Phase IIIb SPARK* study has met its primary endpoint. The results of the first 26 weeks of this study demonstrated that the addition of Kuvan® (sapropterin dihydrochloride) to a phenylalanine-restricted diet in children less than 4 years of age who have phenylketonuria (PKU) and have been previously shown to be responsive to Kuvan significantly increased tolerance to phenylalanine compared with a phenylalanine-restricted diet alone. The safety profile of Kuvan in this population was consistent with the safety profile for Kuvan described in the European Summary of Product Characteristics. The 26-week results will be submitted for presentation at upcoming international scientific meetings and for publication in a peer-reviewed journal. SPARK was requested by the European Medicines Agency (EMA) as a post-authorization measure and demonstrates Merck’s commitment to addressing areas of high unmet medical need. The positive outcome of the study will enable the submission of a regulatory application for a label extension later this year.

Dr John Orloff, Global Head of Clinical Development at Merck’s biopharmaceutical division Merck Serono, underlined the company’s commitment to better management of PKU for all those affected by it: “PKU is a serious rare disease that has a significant impact on patients and their families. We are delighted by the positive outcome of this study, and remain dedicated to further improving our understanding of PKU in infants and young children.”
PKU is an inborn metabolic disorder that causes the toxic accumulation of phenylalanine, an essential amino acid found in all protein-containing foods, in the brain and blood.1,2 Untreated, PKU can lead to intellectual disability, seizures and other serious medical problems.1,2 In many countries, implementation of national newborn screening programs has allowed identification of children with PKU at birth, enabling the management of the disease to begin as early as possible in order to avoid potentially severe neurological damage.3

“This is the first time a controlled study such as this has been conducted in children below 4 years of age with PKU” said Professor Ania Muntau, Klinikum University Munich, Germany, and lead investigator for SPARK. “These study findings with Kuvan in addition to phenylalanine-restricted diet could lead to a new disease management approach to control blood phenylalanine levels right from birth.”

SPARK is a Phase IIIb, multicenter, open-label, randomized, controlled study designed to assess the efficacy, safety, and population pharmacokinetics of Kuvan in patients younger than 4 years old with PKU and who have been previously shown to be responsive to Kuvan in a response test. The study was conducted under a Pediatric Investigational Plan. Patients were randomized to Kuvan (10 mg/kg/day) plus a phenylalanine-restricted diet, or to a phenylalanine-restricted diet alone, for 26 weeks, and the primary endpoint of the study was to compare phenylalanine tolerance achieved in both arms after 26 weeks of treatment. Secondary study endpoints included change in levels of blood phenylalanine during the study period, change in dietary phenylalanine tolerance over time (from baseline to 26 weeks) in both groups, as well as assessment of neurodevelopmental function, growth parameters and safety. The long-term efficacy and safety of Kuvan will be assessed in the study’s 3-year extension period, in which all patients will be offered to receive Kuvan in addition to the phenylalanine-restricted diet.

European marketing authorization was granted for Kuvan in 2008. Kuvan was the first, and remains the only, medication in combination with dietary modifications in Europe designed to reduce the concentration of phenylalanine in the blood and in the brain in those patients who are responsive to Kuvan to prevent the debilitating effects of PKU.4 Kuvan is indicated in patients of all ages with tetrahydrobiopterin (BH4) deficiency, and in those aged 4 years and above with PKU (due phenylalanine hydroxylase enzyme deficiency) who are responsive to Kuvan. Currently, there is no licensed medication in Europe for the treatment of PKU in the 0–4 years age group. Kuvan is marketed by Merck Serono outside the USA, Canada and Japan, by BioMarin in the USA and Canada, and under the name Biopten® by Asubio Pharma in Japan. In the USA and Europe, Kuvan received orphan drug designation.

*SPARK: Safety Pediatric EfficAcy PhaRmacokinetic with Kuvan (sapropterin dihydrochloride)

关键词:默克,Kuvan,苯丙酮尿症,四氢生物蝶呤缺乏症,高苯丙氨酸血症

信息来源:生物谷