IFNβ in Asthma

Interferon Beta (‘IFNβ’) in rhinovirus-induced asthma exacerbations

Synairgen is investigating a novel application of inhaled IFNβ to reduce cold virus-induced asthma exacerbations. This virus is a major trigger for the worsening of asthma symptoms, with up to eight out of ten asthma related emergency department visits being associated with these viral infections. Currently there are limited satisfactory treatments available to address this significant unmet need which is associated with the majority of healthcare spending on asthma.

Background

Asthmatics get no more respiratory viral infections than non-asthmatics but infections are more likely to spread to the lung to worsen inflammation and cause exacerbations. IFNβ is a key mediator of the antiviral response. Professor Donna Davies (a Synairgen Co-Founder) and colleagues at the University of Southampton found a defect in the ability of lung cells from asthmatics to produce IFNβ in response to virus infections, offering an explanation for the increased likelihood of the spread of a virus infection to the lungs (see figure below).

Addition of IFNβ restored the normal antiviral response, suggesting that delivery of IFNβ to the lower airways of asthmatics when they contract a respiratory virus infection could limit the spread of the virus to the lungs and consequent exacerbation (Wark PA et al 2005, J Ex Med, 201:937-47).

In asthma, a lack of IFNβ production in response to virus infection results in the reduced induction of apoptosis (programmed cell death) and prolonged virus survival and replication within virally infected asthmatic cells

The addition of IFNβ restores the ability of virus-infected asthmatic cells to undergo apoptosis in order to clear rapidly the viral infection

Current status

  • Intellectual property was exclusively in-licensed from the University of Southampton for the use of IFNβ in protecting asthmatic and COPD subjects from exacerbations induced by the common cold virus. The patent was granted in the USA in August 2009 and in Europe in May 2010
  • In 2007, Synairgen completed a successful Phase I clinical trial of inhaled IFNβ in atopic non-asthmatic subjects (SG003)
  • In 2009, Synairgen completed a successful Phase I clinical trial of inhaled IFNβ in moderate asthmatic subjects (SG004). In addition to assessing safety in the target population, biomarker data was also evaluated to establish activation of antiviral defences in the lungs of asthmatics. Neopterin, a well-recognised marker of IFNβ antiviral activity, was measured in sputum and statistically significant and dose dependant increases in neopterin levels were seen, indicating activation of antiviral defences in the lung. Additionally, increases in gene expression of three antiviral proteins (MxA, 2-5-OAS and IP-10) were seen, indicating that inhaled IFNβ stimulated a broad antiviral response in the lung. Biomarker data also supports the intended dosing regimen for Phase II studies
  • Synairgen has commenced a Phase II proof of concept study in asthma (SG005) in March 2010

Synairgen has established an advisory panel of world experts on asthma and rhinovirus-induced asthma exacerbations, comprising Professors Jim Gern (Wisconsin, USA), Sebastian Johnston (London, UK), Peter Sterk (Amsterdam, The Netherlands) and Ratko Djukanovic (Southampton, UK). The panel will assist us in developing our IFNβ programme and our understanding of rhinovirus infections in asthma

Asthma statistics

  • There are approximately 23 million asthmatics in the USA1
  • The economic cost to the US is $19.7 billion per year2
  • Asthma accounts for 1.7 million emergency department visits per year in the US1
  • The cost of emergency department visits and in-patient care in relation to asthma is $4.7 billion2
  • Up to 80% of asthma exacerbations which result in emergency department visits are associated with RV infections3
  • 50% of the total cost of the asthma is apportioned to 10% of the asthmatic population with the severest disease4

Information about common colds and rhinovirus (RV)

  • Adults get an average of two to four colds per year, mostly between September and May5
  • Young children suffer from an average of six to eight colds per year5
  • Asthmatics have similar upper respiratory tract (nose and throat) symptoms as non-asthmatics6
  • Asthmatics frequently suffer lower respiratory tract
    (the airways in the lung) infections6

References

  1. American Lung Association. Trends in Asthma Morbidity and Mortality. January 2009 www.lungusa.org
  2. Morbidity & Mortality: 2007 Chart book on cardiovascular, lung and blood diseases produced by National Heart, Lung and Blood Institute
  3. S. King et al, Persistence of Rhinovirus RNA after asthma exacerbations in children. Clin Exp Allergy 2005 May 35 (5) 672-8
  4. P.J. Barnes, B. Johnson, J.B. Klim. The Costs of Asthma. Eur Respir J 1996 9, 636-642
  5. Cold and Flu Guidelines: The Common Cold www.lungusa.org
  6. J.M. Corne et al Frequency, severity and duration of rhinovirus infections in asthmatic and non-asthmatic in dividuals: a longitudinal cohort study. Lancet 2002 Mat 9; 359 (9309):831-4