Traumakine Program description

The Traumakine program focuses on the development of a first pharmacological treatment for acute respiratory distress syndrome (ARDS) and is supported by a grant from the7th Framework Programme for Research and Technological Development of the Cooperation Work Programme: Health-2012. The Traumakine consortium consists of the European Commission as a granting Agency, Faron Pharmaceuticals Ltd. as a Coordinator, and three other participating Partners of the Traumakine program (University College London Hospital (UCLH), University of Torino and University of Turku).

The phI/II clinical study with FP-1201 has indicated significant decrease in mortality of the acute lung injury (ALI)/ARDS patients with good safety profile. A total of 37 ARDS patients were treated at nine hospitals in the UK with highly encouraging results. Interferon-beta was found to be safe and well tolerated in ARDS patients and the optimal tolerated dose was established. The selected pharmacodynamic marker for interferon-beta bioactivity showed clear dose response and the treatment target molecule (CD73) levels were induced during the dosing period. Most importantly, interferon-beta treatment significantly reduced the all-cause mortality at day 28, the primary end point of the study, compared to the control cohort (Bellingan et al. 2014, Lancet Respiratory Medicine). Traumakine was associated with an 81% reduction in odds of 28-day mortality. Based on these highly encouraging results, a much larger clinical trial has been designed.

The key activity of the Traumakine-program is a phase III clinical study aiming at the European marketing authorization of FP-1201-lyo treatment of ARDS, which also has an orphan designation from the European Commission (EU/3/07/505). This second, presently ongoing, clinical trial is a Phase III double-blind, randomised, parallel-group comparison of efficacy and safety of interferon-beta and placebo in the treatment of patients with moderate to severe ARDS. The study, named INTEREST, is taking place in approximately 60 hospitals across Belgium, Finland, France, Germany, Italy, Spain and UK and 300 ARDS patients in total will be recruited.

About ARDS and FP-1201-lyo (lyophilized human recombinant interferon-beta 1a)

ARDS is a serious clinical disorder, which follow a variety of severe direct and indirect lung insults. In serious life threatening situations such as infection leading to sepsis or trauma causing massive tissue injury, an escalation of the systemic inflammatory response leads to multiple organ failure including ARDS. In the case of ARDS, the predominant pathophysiological event is increased vascular leakage, which has been shown to be due to the lack of adenosine, an end product of AMP degradation by 5’-nucleotidase (CD73). Adenosine acts to enhance endothelial barrier function via adenosine receptor activation. Therefore, any biological substance, which acts to increase adenosine level, will reduce vascular leakage and be of benefit in ARDS patients. Such substances are type I interferons, and especially the interferon-beta (IFN-beta). IFN-beta has been shown to up-regulate 5’-nucleotidase (also known as a CD73 molecule and expressed abundantly by normal endothelial cells) and prevent ALI in animal models (Kiss et al. (2007) Eur. J. Immunol. 37:3334). IFN-beta is therefore a potential treatment for ALI/ARDS.

The Traumakine mechanism of action is shown in a video on the front page. The medical need for an effective and safe treatment of ARDS is high, since this condition is life threatening with 35-45 % mortality rate (Rubenfeld et al. (2005) N Engl J Med 353, 1685) (Phua et al. (2009) Am J Respir Crit Care Med 179, 220) and affects close to 175.000 patients in Europe alone. Currently no approved pharmacological treatment of ARDS by the regulatory authorities in Europe is available.