TIDMSNG
RNS Number : 2097C
Synairgen plc
21 February 2022
Synairgen plc
('Synairgen' or the 'Company')
Synairgen announces topline results from Phase 3 SPRINTER trial
in patients hospitalised with COVID-19
Southampton, UK - 21 February 2022: Synairgen plc (LSE: SNG),
the respiratory company developing SNG001, a formulation for
inhalation containing the broad-spectrum antiviral protein
interferon beta, today announces that the international Phase 3
SPRINTER trial of SNG001 in patients hospitalised with COVID-19 did
not meet its primary or key secondary efficacy endpoints. SNG001
demonstrated a favourable safety profile and was well tolerated in
this population.
Richard Marsden, CEO of Synairgen, commented: "While we are
disappointed by the overall outcome, SNG001 has been administered
to hospitalised patients on top of standard of care which changed
substantially between our Phase 2 and Phase 3 trials. This
improvement in patient care may have compromised the potential of
SNG001 to show a clinical benefit in respect of the endpoints for
this study, which were not met. Despite this we have observed an
encouraging trend in prevention of progression to severe disease
and death, which we strongly believe merits further investigation
in a platform trial. We are now analysing the full dataset to
better understand all the findings."
"In the meantime, we eagerly await the Phase 2 data from the US
NIH ACTIV-2 trial in home- based COVID-19 patients, and that
trial's larger, follow-on Phase 3 study, as part of the development
path for SNG001."
Efficacy
A total of 623 patients were randomised to receive SNG001
(n=309) or placebo (n=314) in addition to standard of care (SOC).
The primary analysis was conducted in the intention-to-treat
population (ITT; all randomised patients). Data for the per
protocol population (PP) is also shown. The PP population excludes
patients with major protocol violations that may have confounded
the results.
Primary Endpoints
Regarding the primary endpoints (Table 1), patients who received
SNG001 were no more likely to be discharged from hospital than
patients who received placebo, and patients who received SNG001
were also no more likely to recover to 'no limitation of
activities' than patients who received placebo, in both the ITT and
PP populations. The evolution in standard of care over the course
of the pandemic (for example, 87% of patients in this trial
received systemic corticosteroids for COVID-19 at baseline whereas
none did in the Phase 2 study of SNG001 in COVID-19 ([1]) ) may
have compromised the potential of SNG001 to show a clinical benefit
in respect of the primary endpoints for this study.
Table 1: Primary Endpoints
Population Intention-to-Treat Per Protocol
Endpoint Placebo SNG001 Placebo SNG001
+ SOC (n=314) + SOC (n=309) + SOC (n=261) + SOC (n=256)
---------- --------------- --------------- --------------- ---------------
Time to hospital Median 8 (7,9) 7 (7,8) 7 (6,8) 7 (6,7)
discharge (95% CI) Days Days Days Days
through day
28
---------- --------------- --------------- --------------- ---------------
HR (95% 1.06 (0.89, 1.27); 1.02 (0.84, 1.23);
CI) p=0.509 p=0.846
---------- -------------------------------- --------------------------------
Time to recovery* HR (95% 1.02 (0.81, 1.28); 1.01 (0.79, 1.29);
through day CI) p=0.888 p=0.933
28
---------- -------------------------------- --------------------------------
* to 'no limitation of activities' on the WHO ordinal scale for
clinical improvement (OSCI). HR =Hazard ratio; 95% CI = 95%
confidence intervals. The per protocol population excludes patients
with major protocol violations that may have confounded the
results. These violations included receiving fewer than 2 full
doses in the first 3 days, ongoing SARS-CoV-2 infection for more
than 3 weeks prior to randomisation, not having a positive
SARS-CoV-2 test result at screening, patients kept in hospital for
reason other than the severity of their COVID-19 and patients who
were not escalated to advanced respiratory support despite clinical
need.
Key Secondary Endpoints
For the key secondary endpoints (Table 2), there was a trend in
favour of SNG001 for the endpoint measuring progression to severe
disease or death within 35 days of randomisation with a 27% and 36%
relative risk reduction, for the ITT and PP populations
respectively, in the proportion of patients who were treated with
SNG001 compared to patients on placebo.
Table 2: Key Secondary Endpoints
Population Intention-to-Treat Per Protocol
Endpoint Placebo SNG001 Placebo SNG001
+ SOC (n=314) + SOC (n=309) + SOC (n=261) + SOC (n=256)
--------- --------------- --------------- --------------- ---------------
Progression
to severe
disease or
death within
35 days n (%) 46 (14.7%) 33 (10.7%) 32 (12.3%) 20 (7.8%)
--------- --------------- --------------- --------------- ---------------
OR (95% 0.69 (0.43, 1.12); 0.63 (0.35, 1.13);
CI) p=0.135 p=0.119
--------- -------------------------------- --------------------------------
RRR 27.1% reduction 36.3% reduction
--------- -------------------------------- --------------------------------
Progression
to intubation
or death
within 35
days n (%) 23 (7.3%) 20 (6.5%) 15 (5.7%) 10 (3.9%)
--------- --------------- --------------- --------------- ---------------
OR (95% 0.85 (0.45, 1.61); 0.76 (0.34, 1.72);
CI) p=0.610 p=0.512
--------- -------------------------------- --------------------------------
RRR 11.6% reduction 32.0% reduction
--------- -------------------------------- --------------------------------
Death within
35 days n (%) 17 (5.4%) 14 (4.5%) 12 (4.6%) 7 (2.7%)
--------- --------------- --------------- --------------- ---------------
OR (95% 0.79 (0.38, 1.67); 0.65 (0.26, 1.64);
CI) p=0.544 p=0.363
-------------------------- -------------------------------- --------------------------------
RRR 16.3% reduction 40.5% reduction
-------------------------- -------------------------------- --------------------------------
OR = Odds ratio; 95% CI = 95% confidence intervals, RRR =
Relative Risk Reduction.
Safety
SNG001 was well tolerated in the SPRINTER trial with a
favourable safety profile consistent with previous studies. The
proportion of patients with any serious treatment-emergent adverse
events was 12.3% on SNG001 and 18.2% on placebo. The proportion of
patients with any treatment-emergent adverse events related to
study treatment was 22.3% on SNG001 and 25.7% on placebo.
Next steps
Synairgen will now review the study's full dataset to better
understand the detailed results and implications for development
for SNG001 and will provide an update in due course. The study
results will also be submitted for publication in a peer-reviewed
journal.
Ongoing ACTIV-2 trial
SNG001 is being investigated for possible use in COVID-19
patients at home as part of the US National Institute of Health's
ACTIV-2 trial . In October 2021 Synairgen announced that SNG001 had
been recommended to advance from Phase 2 into Phase 3 in this trial
in mild to moderate COVID-19 patients.
Tom Wilkinson, Chief Investigator and Professor of Respiratory
Medicine, University of Southampton, said: "The results of the
SPRINTER study confirm that inhaled interferon beta can be safely
administered to hospitalised patients with COVID-19. The primary
study endpoints of time to hospital discharge and time to recovery
have not shown a clear treatment benefit. However, there is an
important trend in favour of SNG001 in the secondary outcome
progression to severe disease and death, which aligns to the
findings of the earlier Phase 2 study. Better treatments for severe
disease are still desperately needed but what's clear is that
improvements in outcomes driven by vaccination and the evolution in
standards of care mean that larger studies are required to
definitively explore SNG001's impact on mortality and severe
disease. With the strong safety profile that this treatment now has
shown, it is appropriate for it to be considered by the large
platform studies to confirm efficacy signals in severe
COVID-19."
The Company's current cash balances as of today are in excess of
GBP25 million.
This announcement contains inside information for the purposes
of Article 7 of Regulation (EU) No. 596/2014 ('MAR').
For further enquiries, please contact:
Synairgen plc
Brooke Clarke
Media@syairgen.com
Investors@synairgen.com
Tel: + 44 (0) 23 8051 2800
UK media and investors:
Consilium Strategic Communications
Mary-Jane Elliott/Jessica Hodgson
cscsynairgen@consilium-comms.com
Tel: +44 (0) 20 3709 5700
US Media:
Mary Conway
MConway@MKCStrategies.com
Tel: +1 516-606-6545
finnCap (NOMAD and Joint Broker)
Geoff Nash, Kate Bannatyne, Charlie Beeson (Corporate
Finance)
Alice Lane, Sunil de Silva (ECM)
Tel: + 44 (0) 20 7220 0500
Numis Securities Limited (Joint Broker)
James Black, Freddie Barnfield, Duncan Monteith
Tel: + 44 (0) 20 7260 1000
Notes for Editors
About SPRINTER (SG018) trial
The SPRINTER trial (SG018; NCT04732949) is a global Phase 3,
randomised, placebo-controlled, double-blind, multi-site clinical
trial assessing the efficacy and safety of inhaled SNG001 on top of
standard of care for the treatment of adults hospitalised due to
COVID-19 requiring treatment with supplemental oxygen by mask or
nasal prongs. Patients requiring high-flow nasal oxygen therapy,
non-invasive ventilation, or endotracheal intubation (invasive
ventilation) at randomisation were excluded. COVID-19 was confirmed
using a validated molecular test for the presence of the SARS-CoV-2
virus.
The primary efficacy analysis was performed in the
intention-to-treat population (all randomised patients) by
evaluating the change in clinical condition using the WHO 9-point
Ordinal Scale for Clinical Improvement (OSCI; See Table 1 below)
out to Day 35. Participants will be followed out to Day 90 to allow
the assessment of long-COVID symptoms. The trial had two primary
endpoints, evaluated using Cox proportional hazards modelling:
-- Time to hospital discharge through Day 28, defined by the
OSCI score of 2 or below, with no rebound (readmission) at
subsequent assessments; and
-- Time to recovery to "no limitation of activities" through Day
28, where recovery is defined as the OSCI score of 1 or below, with
no rebound at subsequent assessments.
Key secondary endpoints, analysed using logistic regression,
were:
-- Progression to severe disease or death, defined by the WHO
OSCI score of 5 or above within 35 days of first dose;
-- Progression to intubation or death, defined by the WHO OSCI
score of 6 or above within 35 days of first dose; and
-- Death within 35 days of first dose.
The trial enrolled 623 patients, randomised (1:1) to treatment
with inhaled SNG001 or placebo on top of standard of care at more
than one hundred sites across 17 countries including Argentina,
Belgium, Brazil, Colombia, France, Germany, India, Israel, Italy,
Mexico, Netherlands, Portugal, Romania, Serbia, Spain, the United
Kingdom and the United States.
SNG001 (15.6MIU) or placebo (formulation buffer without
interferon beta) were administered by patients in the hospital, and
at home once discharged, once-daily for up to 14 days using the
Aerogen Solo/Ultra nebuliser.
Table 1: WHO Ordinal Scale for Clinical Improvement (OSCI)
Patient State Descriptor Score
No clinical or virological
Uninfected evidence of infection 0
Ambulatory No limitation of activities 1
Limitation of activities 2
Hospitalized - Mild Hospitalized, no oxygen
disease therapy 3
Oxygen by mask or
nasal prongs 4
Hospitalized - Severe Non-invasive ventilation
disease or high-flow oxygen 5
Intubation and mechanical
ventilation 6
Ventilation + additional
organ support - pressors,
RRT, ECMO 7
Dead Death 8
About SNG001
SNG001 is a pH-neutral formulation of interferon-beta (IFN-beta)
for inhalation that is delivered directly into the lungs using a
mesh nebuliser, currently being investigated as a potential
host-directed antiviral treatment for COVID-19 patients.
The SARS-CoV-2 virus has been shown to suppress the production
of IFN-beta, a naturally occurring protein that orchestrates the
body's antiviral defences, with the aim of evading host immune
responses. By administering IFN-beta into the lungs, the aim is to
correct this deficiency, potentially switching back on the lungs'
antiviral pathways to clear the virus.
About Synairgen
Synairgen is a specialist respiratory biotechnology company
whose primary focus is developing its inhaled IFN-beta candidate
(SNG001) for the treatment of COVID-19 and other severe viral lung
infections. SNG001 has been granted Fast Track designation from the
US Food and Drug Administration (FDA) and its Phase 3 SPRINTER
trial was deemed an Urgent Public Health study by the UK's National
Institute for Health Research (NIHR). Founded by University of
Southampton Professors Sir Stephen Holgate, Donna Davies, and Ratko
Djukanovic in 2003, Synairgen is quoted on AIM (LSE: SNG). For more
information about Synairgen, please see www.synairgen.com .
[1] Monk PD, Marden RJ, Tear VJ, et al. Safety and efficacy of
inhaled nebulized interferon beta-1a (SNG001) for treatment of
SARS-CoV-2 infection: a randomized, double-blind,
placebo-controlled, phase 2 trial. Lancet Respir Med.
2021;9:196-206.
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