vasopharm GmbH Announces Post Hoc Analyses of Clinical Trials in Traumatic Brain Injury
Improved neurologic outcome in young adults (18-39 years) with Ronopterin infused early
Significantly less aggressive critical care with maintained renal function in young adults
New patent filed for efficacious treatment window
Discussions with US and EU regulators to support market authorization initiated
vasopharm GmbH, a privately-held biopharmaceutical company focusing on novel therapeutics to treat cerebrovascular diseases, today announces the combined post hoc analyses of the phase 2 (NOSTRA) and phase 3 clinical trials (NOSTRA III) of Ronopterin (formerly VAS203) for the treatment of traumatic brain injury (TBI). These analyses expand on the clinically meaningful results in patients with moderate and severe TBI with early infusion of Ronopterin, starting between 6 and 12 hours after TBI. Ronopterin has the potential to be the first successful drug therapy for TBI with meaningful improvements in neurologic outcome.
The combined analysis of the phase 2 (NOSTRA) and phase 3 (NOSTRA III) trials reveals a positive and clinically meaningful impact on signs of efficacy and safety when Ronopterin is infused within 12 hours after TBI, particularly in patients aged 18-39 years. With this analysis, NOSTRA III confirms the results of the initial NOSTRA trial.
The early start of infusion with Ronopterin improves neurologic outcome at 6 months after TBI and supports the continuous neurologic improvement over time. The significant reduction in the intensity of basic treatment options reflects better control of increased intracranial pressure. This is best explained by Ronopterin’s mechanism of action: inhibition of excessive nitric oxide-induced cell damage and vasodilation decreases edema formation and brain swelling. In addition, none of the 133 patients aged 18-39 years showed signs of higher grade renal impairment; among the 122 patients aged 40-60 years, 16 patients exhibited fully reversible signs of higher grade renal dysfunction. The combination of Ronopterin-induced better neurologic outcome and complete absence of higher grade renal impairment clearly defines the patients aged 18-39 years as the target patient population for the next trials in the Clinical Development Plan for Ronopterin.
Professor Erich Schmutzhard, Medical University of Innsbruck, Austria and Chief Investigator for the NOSTRA III trial, said:
“I am happy to see strong evidence defining the optimal use of Ronopterin resulting in neuroprotection in patients with moderate and severe TBI. Currently, there is no drug treatment available to improve neurologic outcomes for these patients. For us clinicians it is crucial to have a drug allowing us to prevent and reduce the severity of secondary brain damage. Decreasing the vulnerability of the injured brain will support further maximum neurologic improvement after discharge from the neuro-intensive care unit. It is comforting to see that the improved outcome already disclosed in the prespecified analysis in the young adult patients is now repeated and confirmed in the post hoc analysis. This is very important as the young adults with their long life expectancy must return to their normal life in the best condition possible.”
Neurologic outcome (Glasgow Outcome Scale) in 18-39 years
Combining the 3 time points at 3, 6, and 12 months of the NOSTRA (6, 12 months) and NOSTRA III trial (3, 6 months) shows a continuous neurologic improvement over time in young adults with early start of infusion between 6 and 12 hours after TBI.
The steady decrease in proportion of patients with Unfavorable Outcome (GOS 1-3) is exceeded by a steady increase in Favorable Outcome (GOS 4-5) and Good Recovery (GOS 5) in the Ronopterin group. At 6 months, neurologic improvement appears to level off in the Placebo group with a continuous increase in the Ronopterin-treated patients, reaching highest values at 12 months (Good Recovery at 6 months: Ronopterin vs Placebo: 50% vs 26%; 12 months: 80% vs 20%, p=0.02).
Therapy Intensity Level (TIL) in 18-39 years
The combined analysis reveals a significant increase in proportion of low TIL levels (3-10 points) (Ronopterin vs Placebo: 71% vs 62%, p=0.01), reflecting decreased aggressiveness of treatment measures required to reduce ICP. Ronopterin’s TIL reducing effect is highest during the second week after TBI (81% vs 64%, p=0.0002).
Renal function in 18-39 years
Clinically relevant reduction in renal function (AKIN level 2 and 3) was never observed in patients aged 18-39 years neither in the NOSTRA nor the NOSTRA III trial. This underscores the positive benefit-risk profile for the use of Ronopterin in young critically ill adult patients with moderate and severe TBI.
Professor John Stover, Chief Medical Officer of vasopharm, explained:
“We are very excited about this robust and resilient data base. We can confirm the key results from the initial trial with the results of the corresponding NOSTRA III patients with early start of infusion. This strongly substantiates our conviction to move forward with Ronopterin. vasopharm will discuss with EMA and FDA the new Clinical Development Plan in the next months to support the market authorization application.”