KeyNeurotek Pharmaceuticals Reports Breakthrough In The Treatment Of Patients With Severe Traumatic Brain Injury In A Phase IIa Study
Published: Dec 14, 2009
Magdeburg, December 16, 2009 – KeyNeurotek Pharmaceuticals AG, a biotechnology company focused on the development of drugs against degenerative disorders of the central nervous system and autoimmune diseases, today reports a positive outcome of its Phase IIa study with KN38-7271 in patients with severe traumatic brain injury (TBI). The data substantiate pharmacokinetics, safety and tolerability of the substance – a dual cannabinoid receptor agonist – and show clear signs of therapeutic efficacy in this indication. Currently, there is no pharmaceutical treatment available to patients suffering from traumatic brain injuries. The pharmacokinetic analysis of the clinical data shows that the study met its primary endpoint, demonstrating a dose-dependent blood plasma concentration of KN38- 7271. In addition, KN38-7271 was found to be safe and well tolerated. Most importantly, this is the first major clinical study investigating pharmaceutical interventions in severe TBI, where several parameters suggest therapy-relevant efficacy of KN38-7271: ? Survival rate of patients receiving the study drug was statistically significantly increased 30 days after start of treatment in both dosage groups. ? KN38-7271-treated patients, regardless of the dose applied, showed trends toward a better neurological outcome, e.g. improved orientation and amnesia 3 or 6 months after TBI. ? The intracranial pressure (ICP) which is usually increased in TBI patients and threatens survival of the brain, was lowered in KN38-7271-treated patients. ? Consistently, the slope of ICP elevation over the first days after TBI was flattened and the time of the highest ICP was considerably delayed in the KN38- 7271-treated groups. ? Cerebral perfusion pressure (CPP), which promotes oxygen and glucose supply of the brain and needs to be maintained within certain limits, was positively influenced in the drug-treated patients. The study strongly supports the mode of drug action of KN38-7271 as a dual cannabinoid CB1 and CB2 receptor agonist. This Phase IIa trial and met the highest quality criteria in terms of patient recruitment, randomization and homogeneity as well as protocol compliance, design, and a low number of patient withdrawals. The double-blind, placebo-controlled proof-of-concept study included 97 adult comatose TBI patients and was performed in three European countries, including Germany, to investigate the pharmacokinetics, safety and efficacy of two dose levels of KeyNeurotek’s lead compound KN38-7271. Prof. Dr. med. Raimund Firsching, European coordinator of this study, stated: "KeyNeurotek’s TBI study is clearly setting a quality benchmark. Besides, it is exciting to see for the first time signs of potential drug efficacy on the basis of improved survival of severe TBI patients." Prof. Dr. med. Jürgen Piek, Coordinating investigator added: " This study conveys a very comprehensive picture, underlining the therapeutic potential of KN38- 7271 and providing clear guidelines for the design of subsequent Phase II/III studies.” Dr. Frank Striggow, CEO of KeyNeurotek Pharmaceuticals, summarized: “We are extremely pleased with the quality and the outcome of this very important study which has exceeded our expectation and is also encouraging for other indications such as stroke. I would like to thank all KeyNeurotek employees and collaborators involved in preparing, performing and analyzing this leading international study. Based on the data and the Orphan Drug Designation of KN38-7271 for the treatment of moderate and severe closed TBI, we will now talk to the European Medicines Agency about the next steps." About Traumatic Brain Injury Traumatic brain injuries are usually caused by accidents or assaults, and the death rate is dramatically increasing with the severity of the injury. Moreover, survivors carry a high risk of permanent neurological disabilities. With more than 700,000 hospitalized patients in the USA and Western Europe, TBI is one of the major reasons for death and severe disabilities among younger adults. It is also one of the major injuries in military conflicts. At present, there is no pharmaceutical treatment option available. KeyNeurotek Pharmaceuticals is among the leading developers of drugs for this indication. The potential annual market potential of drugs improving the clinical outcome of TBI patients has been estimated to exceed US$1 billion.1 KeyNeurotek’s drug candidate KN38-7271 is characterized by an innovative, dual mode of action. As a cannabinoid receptor agonist, it activates CB1- and CB2- receptors on nerve and immune cells. It thereby enhances natural protection mechanisms and at the same time prevents critical inflammatory responses. Four earlier Phase-I-studies with healthy volunteers have demonstrated that KN38- 7271 is safe and well tolerated. In September 2008, KeyNeurotek's compound was granted Orphan Drug Designation for the treatment of moderate to severe closed traumatic brain injury by the EU authorities. About KeyNeurotek Pharmaceuticals AG KeyNeurotek Pharmaceuticals, a privately held biotechnology company, was founded in 2000 within the Magdeburg region in Germany, one of the leading centers of neuroscience in Europe. The company pursues a number of drug candidates in various preclinical and clinical stages. The most advanced compound, KN38-7271, is in clinical development for TBI and stroke. KeyNeurotek Pharmaceuticals has unique functional and tissue-based high throughput screening platforms for compatible ex vivo and in vivo studies (TELOMICSTM). Based on its know-how, KeyNeurotek develops innovative therapies for the treatment of various neurodegenerative diseases of the central nervous system, such as traumatic brain injury, stroke, Alzheimer's disease and urinary incontinence/overactive bladder. The company has built a strong network with renowned local and international partners, including, among others, the Leibniz Association, the Max Planck Society and Fraunhofer Society, Evotec, Schwarz Pharma/UCB, Bayer Schering and Gruenenthal. KeyNeurotek has been awarded the Hugo-Junckers Innovation Award of the State of Sachsen-Anhalt in 2002 and 2004 and the Innovation Award of the German Industry in 2006.