TIDMSNG
RNS Number : 8968R
Synairgen plc
27 September 2017
Press release
Synairgen plc
('Synairgen' or the 'Company')
Data update from clinical trial of inhaled interferon beta
(SNG001) and clinical plan for COPD
- Significant positive findings in patients with a confirmed
viral infection in the INEXAS trial
- COPD Phase II clinical trial designed
Southampton, UK - 27 September 2017: Synairgen (LSE: SNG), the
respiratory drug discovery and development company, today provides
a positive update on the development of its inhaled interferon beta
programme (SNG001) and outlines its strategy to move into the
substantial Chronic Obstructive Pulmonary Disease (COPD)
market.
Synairgen has conducted a further analysis of clinical data from
AstraZeneca's INEXAS trial in asthma, based on whether patients had
a positive test for common respiratory viruses.
The aim of treatment with SNG001 is to boost the lungs'
antiviral defences and prevent viruses causing exacerbations of
respiratory disease.
Key new findings from the INEXAS trial (details in 'Detailed
findings and background information" section below):
-- 48% of patients in the trial had a positive test result for a respiratory virus
-- Statistically significant changes in morning lung function
and asthma control were observed in the virus-positive 'difficult
to treat' patients who received inhaled IFN-beta; the same patient
classification in which we had found the positive signal in our
previous Phase II clinical trial (SG005)
Two Phase II trials (SG005 and INEXAS) suggest that SNG001
boosts antiviral responses in the lungs, has a beneficial effect on
lung function and, in more difficult to treat patients, improves
asthma control during cold infections. However, the unexpectedly
low exacerbation rate (<10%) in the INEXAS trial population
suggests that the economic viability of the drug in an asthma
indication would be limited.
Viruses have often been isolated from samples collected from
patients who have had an exacerbation of COPD and with COPD being
the second most common cause of emergency admissions to hospital(1)
it has always had the potential to be a substantial opportunity for
a broad spectrum anti-viral. We have already shown in in vitro
models that SNG001 protects the lung cells of COPD patients when
infected with viruses that cause exacerbations such as flu and the
common cold. However, up until now, our ability to identify those
patients who may benefit from an inhaled anti-viral therapy made
the design of a prospective study challenging. This is because
exacerbations of COPD can be caused by other factors such as
bacterial infections. Two key developments during 2017 have changed
this landscape, opening up a route to the COPD market place for
SNG001 and enhancing the prospects of achieving success in the
clinical development phase:
First, studies in COPD patients published in 2017 suggest that,
looking at all colds in the study period, the risk that a cold will
cause an exacerbation of COPD is around 50%(2) and could be even
higher in particular at risk patients(3) , making COPD a very
attractive market. The exacerbation rate in the INEXAS and Aviragen
trials in asthma was below 10%.
Secondly, a novel point of care diagnostic tool has been
developed which enables rapid confirmation of the existence of a
respiratory viral infection when patients present themselves at the
hospital or trial site. This enables us to treat only those
patients who are infected with a virus, significantly reducing the
number of subjects required to show the potential effect of SNG001.
Clearly this has significant benefits in the future, allowing
accurate prescribing of an anti-viral therapy quickly to those
patients who could benefit from treatment.
Synairgen's strategy for its wholly-owned SNG001 programme is to
progress into clinical development in COPD. The Company has
therefore designed a short trial for the winter of 2017/18 to
evaluate the potential of SNG001 in COPD, which is being submitted
for regulatory approval. In parallel, we are considering optimal
financing strategies to enable us to progress this exciting
development over the medium term.
Richard Marsden, Chief Executive Officer of Synairgen, said: "We
have long been conscious that COPD is the key target market for a
broad spectrum antiviral such as SNG001. Until recently, the
difficulties of patient selection and the associated cost of the
required trials made it prohibitively expensive to pursue. The fact
that high viral exacerbation rates are now evident, combined with
the launch of an effective diagnostic for viral infections, means
that a COPD programme is now both highly attractive and
economically viable.
"Finally, our new analysis of the INEXAS trial data suggests a
complementary result to our previous trial indicating that we can
improve important clinical endpoints in the lungs, which increases
our confidence as we move into the significant opportunity that is
COPD."
Prof. Tom Wilkinson, Chief Investigator for the forthcoming COPD
trial, commented: "The impact which COPD has on millions of
patients' lives is one of the major unmet clinical problems of
modern medicine. The problem of exacerbations of COPD - when
patients become acutely unwell - is a particular issue and leads to
many thousands of admissions to hospital every year, many more than
other common respiratory diseases such as asthma.
"A key cause of these exacerbations is viral infections such as
the common cold and currently we have little or no effective
treatments to limit the effects of these pathogens. Our own work in
Southampton has established the exact nature of the infections
which trigger exacerbations. This clinical trial of a new therapy
is an important step forward in exploring better treatments for
these important events."
-Ends-
For further enquiries, please contact:
Synairgen plc
Richard Marsden, Chief Executive Officer
John Ward, Finance Director
Tel: + 44 (0) 23 8051 2800
finnCap
Geoff Nash, James Thompson (Corporate Finance)
Stephen Norcross, Simon Johnson (Corporate Broking)
Tel: + 44 (0) 20 7220 0500
Consilium Strategic Communications (Financial Media and
Investor
Relations)
Mary-Jane Elliott / Philippa Gardner / Laura Thornton
synairgen@consilium-comms.com
Tel: +44 (0) 20 3709 5701
Detailed findings and background information
About the INEXAS trial:
In the INEXAS trial 121 patients were randomised to receive the
broad spectrum 'antiviral' protein inhaled IFN-beta or placebo when
suspected of suffering a respiratory virus. The primary endpoint
was to assess whether inhaled IFN-beta could reduce the number of
exacerbations caused by cold infections. The trial was stopped
early because too few exacerbations were occurring to enable a
determination of the efficacy of IFN-beta on this endpoint;
furthermore enough patients had been entered into the trial to
assess secondary endpoints. Less than 10% of patients had a severe
exacerbation of asthma in the INEXAS trial (very similar to the
rate (7%) in a trial conducted by Aviragen, which also reported in
2017). This low rate makes inhaled IFN-beta challenging to develop
in asthma as the exacerbation endpoint is important for healthcare
providers; essentially the virus-driven exacerbation of asthma does
not occur frequently enough to make the drug health economically
viable.
AstraZeneca returned the asset and the INEXAS data to Synairgen
in April 2017 quoting "strategic reasons"; at that time the data
from the trial showed elevation in a marker of antiviral activity
(serum IP-10/CXCL-10) and a faster recovery on the lung function
parameter Peak Expiratory Flow Rate (PEFR). Changes in other
endpoints were not clinically relevant, providing little
opportunity for the drug to have an effect.
At the end of July, Synairgen received data confirming which of
the 121 patients had a positive respiratory virus test. 48% of
patients had a confirmed respiratory virus. Exploratory analysis of
the data from these patients and patients who are also in the
British Thoracic Society (BTS) Step 4/5 'more difficult to treat'
category of asthma showed that the drug had a positive effect on
lung function as measured by morning Peak Expiratory Flow
(difference of 38.59 L/min/day days 1-7 p=0.0208, n=18 in active
group, 19 in placebo group) and also on asthma control over the
first week of treatment (Asthma Control Questionnaire or ACQ)
difference of -0.492, p=0.0320 n=16 in active group, 21 in placebo
group). This data is similar to the findings from our own trial
(SG005) of inhaled IFN-beta(4) : PEF change of 31.42 L/min/day days
2-14 p=0.029 (n=22 in active group, 25 in placebo group) and ACQ
-0.63 p=0.004 (n=27 in active group, 31 in placebo group) who also
came from the BTS Step 4/5 category of asthma (n=24 in active
group, 30 in placebo group).
COPD
Chronic Obstructive Pulmonary Disease (COPD) is a lung condition
characterised by airflow limitation that is not fully reversible.
This airflow limitation is normally progressive and is associated
with an abnormal inflammatory response of the lung to pathogenic
stimulus. The majority of COPD is associated with long-term
cigarette smoking. Symptoms of COPD include cough, excessive sputum
production and shortness of breath.
Exacerbations of COPD are defined as the worsening of COPD
symptoms beyond normal day-to-day variations and are associated
with irreversible loss of lung function and, therefore, accelerated
disease progression. Exacerbations severely impact on the patient's
quality of life (patients typically take a number of weeks to
recover) and are a major healthcare burden. Exacerbations are
currently treated with oral corticosteroids and antibiotics.
Systemic administration of corticosteroids is associated with
unwanted side effects and there is a drive to reduce antibiotic
usage.
Respiratory viral infections, such as the common cold and flu,
are a major driver of exacerbations in patients with lung disease
when infections spread from the upper respiratory tract to the
lungs to worsen pre-existing lung inflammation. Furthermore,
particularly in COPD, there is growing evidence that virus
infections increase susceptibility to follow on bacterial
infections. Therefore, there is strong rationale to develop
anti-viral treatments to prevent or treat exacerbations of
COPD.
COPD statistics
-- COPD is the 3rd leading cause of death worldwide (after heart attack and stroke)(5)
-- US national medical costs attributable to COPD and its
consequences were estimated at $32 billion in 2010 and are forecast
to increase to $49 billion in 2020(6)
-- More than 15 million Americans have COPD(7)
-- In 2010 there were 715,000 hospitalisations for COPD in the USA(8)
-- The average cost of a hospitalisation in 2010 for a COPD patient was $7,400(9)
Planned COPD trial:
The trial plan involves dosing a small cohort of stable
un-infected COPD patients with SNG001 or placebo to confirm safety
in the new indication and show upregulation of anti-viral
biomarkers. In the second part of the trial, up to 80 patients will
receive either SNG001 or placebo. The objectives of this study are
to ensure that antiviral pathways are elevated in COPD patients
with a confirmed respiratory virus, and to assess other clinically
important endpoints to guide the design of a Phase IIb trial (in
which the effect on acute exacerbations will be assessed).
Point-of-care diagnostic:
Although exacerbations of asthma are less predictable than
expected, when they do occur they are highly likely to be caused by
viruses, as rhinovirus infections account for 50% to 80% of asthma
exacerbations in both children and adults(9) . In COPD, other
triggers can cause exacerbations, and it is less clear as to
whether cold symptoms can be easily identified over and above COPD
symptoms. Recently, a point of care test has been launched that has
made entry into COPD much easier; it is now possible to confirm the
presence of a virus in about 1 hour. This means that COPD patients
presenting with cold like symptoms or COPD symptoms will only be
entered into the trial if they test positive for a respiratory
virus making trials more efficient, and paving a route to
market.
References
1. Department of Health. An Outcomes Strategy for Chronic
Obstructive Pulmonary Disease (COPD) and Asthma in England.
Published July 2011.
2. Johnston NW, et al. Colds as predictors of the onset and
severity of COPD exacerbations International Journal of COPD
2017:12: 839-848
3. Wilkinson TMA, et al. A prospective, observational cohort
study of the seasonal dynamics of airway pathogens in the aetiology
of exacerbations in COPD Thorax 2017;0:1-9.
Doi:10.1136/thoraxjnl=2016-209023
4. Djukanovic R, et al. The Effect of Inhaled IFN-<BETA>
on Worsening of Asthma Symptoms Caused by Viral Infections. A
Randomized Trial. Am J Respir Crit Care Med 2014 Jul 15; 190(2):
145-154
5. World Health Organisation. Available at http://www.who.int/mediacentre/factsheets/fs310/en/
6. Earl S et al. Total and State-Specific Medical and
Absenteeism Costs of COPD Among Adults Aged = 18 Years in the
United States for 2010 and Projections Through 2020. Chest.
2015;147(1):31-45
7. https://www.nhlbi.nih.gov/health/educational/copd/what-is-copd/index.htm
8. American Lung Association: Trends in COPD (chronic bronchitis
and emphysema): Morbidity and Mortality. March 2013. Available at
http://www.lung.org/finding-cures/our-research/trend-reports/copd-trend-report.pdf
9. Costs for Hospital Stays in the United States, 2010. Available at https://www.hcup-us.ahrq.gov/reports/statbriefs/sb146.pdf
10. J.T. Kelly et al. Host immune responses to rhinovirus:
Mechanisms in asthma. J Allergy Clin Immunol 2008; 122: 671-682
This information is provided by RNS
The company news service from the London Stock Exchange
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