Date: 2012-09-17
Type of information:
phase: 2a
Announcement: results
Company: Vasopharm (Germany)
Product: VAS203
Action
mechanism: VAS203 is an allosteric NO synthase inhibitor. It rapidly lowers excessive NO production and controls the deleterious consequences of CHI in a region-specific manner. In pre-clinical, proof-of-principle studies, application of VAS203 had a positive and significant effect on reduction of ICP increase as well as on neurological outcome, measured in behavioural tests. VAS203 is the first drug which targets both blood vessels and tissue of the brain and represents a completely novel pharmacological approach.
Disease: traumatic brain injury
Therapeutic area: Traumatology - CNS diseases
Country: Spain, England, Austria, France, Switzerland
Trial
details: The NOSTRA (NO-Synthase inhibition in TRAumatic brain injury) trial was a European, multicentre, placebo-controlled, double blind study with safety and tolerability as primary endpoints. The study employed ‘in vivo’ microdialysis to monitor pharmacodynamic and pharmacokinetic properties of the compound VAS203. VAS203 is a novel allosteric NO-synthase antagonist which interrupts the inducible nitric oxide process involved in brain swelling.
In total, 32 patients with moderate to severe traumatic brain injury were enrolled in three cohorts in six study centres in Spain, England, Austria, France and Switzerland. All study centres used continuous microdialysis to monitor cerebral energy household, NO metabolism and concentration of the drug in the brain tissue. VAS203 was administered in addition to standard of care treatment.
Latest
news: * On September 17, 2012, vasopharm GmbH, a pharmaceutical company dedicated to the discovery and development of novel therapeutics for the treatment of cerebro- and cardiovascular diseases, has announced that the explorative phase IIa NOSTRA trial in traumatic brain injury patients met all clinical endpoints for safety and in addition demonstrated strong evidence of clinical benefit in patients.
Final analysis of the data showed that all clinical endpoints were achieved: the drug demonstrated good safety and tolerability and reached the brain tissues in pharmacologically relevant amounts. Furthermore, mortality was 12.5% in the placebo group versus no deaths in the drug group.
VAS203 did not have any negative effect on the cerebral perfusion pressure. The Therapy Intensity Level (TIL) – a marker evaluating concomitant therapy and intervention by the physicians as a measure for control of intracranial pressure (ICP) – demonstrated a substantial reduction in VAS203 treated patients compared to placebo. Interpretation of data on ICP – often used as a surrogate endpoint in TBI clinical trials – is impractical without reference to the intensity of therapy directed at controlling ICP.
In addition the extended Glasgow Outcome Scale (eGOS) was used off protocol to assess the level of achieved neurological recovery six months post-injury. In comparison to the placebo group, the eGOS determined at six months post-injury, was significantly increased demonstrating a substantially improved recovery in patients receiving VAS203 (p = 0.006).
Vasopharm is now seeking a strategic partner to accelerate the further development of VAS203.
* On April 19, 2012, vasopharm GmbH has announced the completion of patient treatment in the phase IIa NOSTRA trial (NO-Synthase inhibition in TRAumatic brain injury). The company expect to complete sample and data analysis by Q3 2012.
