Date: 2014-01-02
Type of information: Publication of results in a medical journal
phase: 1-2
Announcement: publication of results in The Lancet Respiratory Medicine
Company: Faron Pharmaceuticals (Finland)
Product: Traumakine® - FP-1201 (human recombinant interferon-beta 1a)
Action
mechanism: protein. FP-1201 is a human recombinant interferon-beta 1a. In acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), the predominant patho-physiological result 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 ALI/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).
Disease: acute lung injury (ALI) , acute respiratory distress syndrome (ARDS)
Therapeutic area: Lung diseases - Respiratory diseases
Country: UK
Trial
details: The purpose of this phase 1/2 open-label study was to assess the safety, tolerability and preliminary efficacy of FP-1201 (Interferon Beta) in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). (NCT00789685)
Latest
news: * On January 2, 2014, Faron Pharmaceuticals announced that the FPCLI001 study, which reduced the odds of all cause mortality by more than 80 percent among the ARDS patients, has been published online in The Lancet Respiratory Medicine. The published research article incorporates both molecular studies of Professor Sirpa Jalkanen (University of Turku, Finland) and a clinical study set up sponsored by Faron Pharmaceuticals. The clinical study (phase I/II) was conducted in 8 intensive care units around the UK and led by Dr Geoff Bellingan MD PhD from the University College London Hospitals. The clinical study demonstrated a significant reduction in mortality in ARDS patients. All other measured parameters, e.g. length of mechanical ventilation needed, length of ICU stay and support of vital functions also clearly benefitted from the treatment. Faron is waiting for EMA advise to start phase III studies. (Bellingan G, Maksimow M, Howell D, Stotz M, Beale R, Beatty M, Walsh T, Binning A, Davidson A, Kuper M, Shah S, Cooper J, Waris M, Yegutkin G, Jalkanen J, Salmi M, Piippo I, Jalkanen M, Montgomery H, Jalkanen S (2014) The effect of intravenous interferon-beta-1a (FP-1201) on lung CD73 expression and on acute respiratory distress syndrome mortality: an open-label study. The Lancet Respiratory Medicine 2014: 2: 98-107.) * On September 9, 2013, Faron Pharmaceuticals announced that significant amount of new data was presented at the annual European Respiratory Society (ERS) meeting in Barcelona. The invited lecture was given by prof. Sirpa Jalkanen (University of Turku, Finland) during the lunch session organized jointly by the ERS and the New England Journal Medicine. The topic of the session was “Novel Strategies for Ventilating Patients with ARDS”. The FPCLI001 study group has previously reported a significant reduction in all cause mortality between FP-1201 treated and non-treated ALI/ARDS patients (8,1 % versus 32,2 % with p = 0,01). Now the presentation also included data on secondary end points, which all supported the view that the FP-1201 treatment improved, not only lung function but other organ functions as well. Needs for both vasopressors and hemodialysis were reduced by half compared to non-treated ALI/ARDS patients. Also the data on several biomarkers indicated positive body response to FP-1201 treatment, including a strong decline in IL-6/IL-8 plasma content following the treatment initiation. High IL-6 content in serum has been previously connected to poor outcome of ALI/ARDS patients. * On May 21, 2012, Faron Pharmaceuticals announced that the FPCLI001 Study Group has presented new data from the phase I/II clinical trial in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) at the 2012 American Thoracic Society (ATS) meeting in San Francisco, USA. The trial was performed during 2009-2011 by eight UK based ICU sites and tested safety, tolerability and initial efficacy of FP-1201 on ALI/ARDS patients. The optimal tolerated dose of FP-1201 (10 ?g daily for six days) was considered safe and well tolerated, and also resulted in maximal biomarker stimulation (MxA). The overall mortality of the 37 patients treated with FP-1201 was only 8.1%, four-fivefold less than the expected mortality rate based on the Apache II score value of this group (Apache II value 21.5), normally used to predict the outcome of ALI/ARDS patients. The control group (N=59), which was eligible for the trial but not possible to recruit for administrative reasons, received the best available ICU care but lacked FP-1201 treatment. The mortality and other key parameters of this group were now studied from the hospital records under ethics approval. The mortality of the eligible but not FP-1201 treated group at day 28 was 32.2%. This is four fold higher than with the FP-1201 treated group and is clearly more close to the predicted mortality of their mean Apache II score value of 23.0. The difference in mortalities between the FP-1201 treated and non-treated groups was significant with p value of 0.0069. * On October 7, 2011, Faron Pharmaceuticals has announced that the phase I/II clinical trial in acute lung injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) has ended and the trial database has locked. The primary efficacy end point of the trial was all cause mortality at day 28. This is the only primary efficacy end point accepted by the European Medicines Agency (EMA) that can be used to obtain regulatory approval for products to treat ALI/ARDS. Faron has previously reported that the usually observed 35-40 % mortality of hospitalized ALI/ARDS patients was reduced to 8.1 % among the FP-1201-treated patients. The trial also included a long-term secondary end point, mortality at six months (M6). During this M6 follow-up time only one patient died (due to an intercurrent condition). The overall mortality rate of the FPCLI001 trial at M6 was thus 10.8 %. * On April 12, 2011, Faron Pharmaceuticals has announced that its Phase I/II clinical trial FPCLI001 has completed recruitment for the second and final part of the study. The first part of this clinical trial tested the safety and tolerability of escalating doses of FP-1201 in patients with Acute Lung Injury (ALI) and its more severe form Acute Respiratory Distress Syndrome (ARDS). This part of the study was successfully completed in August 2010 and identified the optimal tolerated dose (OTD) of FP-1201. The OTD was subsequently used in the second part of the study and 22 patients were treated. In addition to safety and tolerability, the second part of the study also studied the preliminary efficacy of FP-1201.The whole study included assessment of several biomarkers as surrogates to elucidate the FP-1201 mechanism of action. The primary end point of the study, all cause mortality at day 28, is the only efficacy end point accepted by the EMA for ALI/ARDS studies. Faron expects to have both primary end point and biomarker data available during Q2-2011.
The whole trial also included assessment of several biomarkers as surrogates to elucidate the mechanism of action of FP-1201. This analysis has revealed that some of the tested biomarkers can provide important information about the progress of ALI/ARDS and treatment efficacy of FP-1201. The company plans to publish this data shortly. The most promising biomarkers will be included in the forthcoming pan-European phase III clinical trial.
