Vasopharm Provides Update on Phase III Traumatic Brain Injury Trial
50% of patients enrolled in trial triggers interim data review
vasopharm GmbH, a privately held biopharmaceutical company, today announced that it has recruited half of the 220 patients in the ongoing, pivotal European NOSTRA III (NO Synthase in TRAumatic Brain Injury) clinical trial. This milestone triggers an interim review by the Data Monitoring Committee (DMC) in line with the agreed study protocol. Allowing for the six month extended Glasgow Outcome Scale (eGOS) evaluation for the 110th eligible patient recruited, the company expect feedback from the DMC in Q4 2018.
NOSTRA III is designed to assess the efficacy and safety of Ronopterin (VAS203) for the treatment of moderately to severely injured closed head traumatic brain (TBI) injury patients, for which there is no existing drug treatment. Traumatic Brain Injury is the leading cause of death and disability among young adults in the developed world. Annually, within the US alone, head trauma is the cause of about two million emergency room visits, roughly 475,000 hospital admissions, nearly 52,000 deaths and approximately 80,000 cases of severe long-term disability (e.g. functional and cognitive disorders, learning disabilities). Direct costs attributed to the treatment of TBI exceed $10bn p.a. in the US alone.
NOSTRA III is a randomised, double-blind, placebo-controlled trial. The study will enroll 220 patients who have suffered a moderate to severe TBI resulting in hospitalisation and who have received an intra-cranial pressure probe. Currently, 35 European neuro-trauma centres in Germany, Austria, France, UK and Spain are participating. The primary endpoint is the eGOS evaluated at six months after the injury. Secondary efficacy assessments include Quality of Life (QOLIBRI) as well as Therapy Intensity Level (TIL) over 14 days after brain injury. NOSTRA III is a registration trial which seeks to validate the data from the highly significant NOSTRA II trial.* The study aims to confirm the data from a Phase II trial in which VAS203 has shown a (2 point) improvement in the extended Glasgow Outcomes Score.
Christian Wandersee, Chief Executive Officer of Vasopharm, commented:
“We are delighted to have reached such a significant milestone in the development of Ronopterin for the treatment for moderate to severe TBI. If NOSTRA III confirms the highly significant data seen in our NOSTRA II trial, we believe we can offer patients and physicians a therapeutic option to ameliorate the devastating and life-long consequences of TBI, where no such option currently exists.”
In addition, Vasopharm announces the successful completion of a Phase Ic trial characterising Ronopterin´s pharmacology in the kidney. This study was conducted in support of the ongoing (NOSTRA III) trial in moderate to severe TBI. Ronopterin is a selective iNOS inhibitor and the kidney is the only organ in which this enzyme plays a constitutive role. The kidney is therefore the most sensitive barometer of undesirable side effects of the drug. The study enrolled 16 healthy male volunteers in a single centre, double-blind, randomised, placebo controlled, cross-over study. Ronopterin was infused over 6 hours with a 4-fold higher infusion rate than that being used in the on-going NOSTRA III trial. There were no drug related adverse events and the safety profile of Ronopterin as examined in this study was excellent. These data indicated no clinically relevant systemic effects following treatment with Ronopterin, in particular tubular function was not affected.
Ronopterin is administered by venous infusion over 48 hours post trauma. Prior to commencing clinical studies the company undertook an extensive formulation program which resulted in a drug formulation that is a highly stable lyophilised powder, easily re-constituted to an isotonic, pH neutral solution for infusion. The company is pleased to announce the granting of worldwide patent protection for several key steps in the synthesis and formulation of Ronopterin.
*Journal of Neurotrauma 31:1599-1606 (October1 2014).
For further information, please contact:
Christian Wandersee, CEO
Optimum Strategic Communications
Mary Clark, Eva Haas, Hollie Vile
Tel: +44 (0) 203 174 1789
NOTES TO EDITORS
About Vasopharm GmbH:
Vasopharm is a drug development company focused on small molecule therapeutics for treatment of Traumatic Brain Injury (TBI). Vasopharm’s lead drug candidate VAS203 (Ronopterin) is currently in the Phase III NOSTRA trial assessing efficacy and safety of VAS203 for the treatment of moderately to severely injured closed head traumatic brain injury patients.
Current approaches to the treatment of acute TBI focus on short term patient mortality and have no significant impact on reducing long-term physical and cognitive deficits. VAS203 avoids unwanted side effects, combined with unprecedented clinical efficacy. The European regulator, EMEA has granted the drug orphan drug designation for moderate to severe brain injury.
Vasopharm was founded in July 1998 as a spin-off from the University of Würzburg Medical School by Harald Schmidt, MD, PhD, Professor of Pharmacology and Toxicology, and Ulrich Walter, MD, Professor of Clinical Biochemistry and Pathobiochemistry. To date, the company has raised Euros 42 million to date through several financing rounds from various Family Investment Offices and Venture Investors including: Bayern Kapital, EF Investments, Fort Rock Capital, Future Capital, Hanseatic Asset Management, Heidelberg Capital Private Equity, KFW and Ringtons Holdings.
See www.vasopharm.com for further details.
About Traumatic Brain Injury:
Traumatic brain injury (TBI) occurs when a sudden trauma causes damage to the brain. Every year, over 1,600,000 patients sustain a traumatic brain injury in the EU, and 70,000 of these die, with a further 100,000 being left disabled. Significantly, 75% of the victims are children and young adults, and TBI is the leading cause of disability in people under 40 years of age. Traumatic brain injury results in more lost working years than cancers, stroke and HIV/AIDS together. On a global scale, the number of life years lost due to traumatic brain injury is four times that of diabetes-related loss. Recent statistics show a steep increase in the incidence of TBIs, with an increase of 21% over the last five years – threefold greater than the rate of increase in population, at an annual cost of over Euros 100 billion. Despite this, TBI has been seriously under-represented in medical R&D efforts compared to many other, less significant health problems.1
VAS203 is an analogue of the natural co-factor tetrahydrobiopterin, which is involved in the generation of nitric oxide by the Nitric Oxide Synthase (NOS) family of enzymes. The mechanism of action of VAS203 is believed to confer selective down regulation of inducible NOS (iNOS) without significantly inhibiting the function of other NOS enzymes. It is believed that iNOS has a significant involvement in the cascade of damaging sequellae following a traumatic brain injury. Technical: VAS203 is (4-amino-(6R,S)-5,6,7,8-tetrahydro-L-biopterin dihydrochloride dihydrate) a structural analogue of (6R)-5,6,7,8-tetrahydro-L-biopterin, the natural endogenous cofactor of NOS and phenylalanine hydroxylase.