REG - Synairgen plc - Topline results from Phase 3 SPRINTER trial

SynairgenAnnouncement

21/02/2022 07:00

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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 + SOC (n=314)  SNG001 + SOC (n=309)  Placebo + SOC (n=261)  SNG001 + SOC (n=256)
 Time to hospital discharge through day 28  Median (95% CI)  8 (7,9) Days           7 (7,8) Days          7 (6,8) Days           7 (6,7) Days
                                            HR (95% CI)      1.06 (0.89, 1.27); p=0.509                   1.02 (0.84, 1.23); p=0.846
 Time to recovery* through day 28           HR (95% CI)      1.02 (0.81, 1.28); p=0.888                   1.01 (0.79, 1.29); p=0.933

* 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 + SOC (n=314)  SNG001 + SOC (n=309)  Placebo + SOC (n=261)  SNG001 + 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% CI)  0.69 (0.43, 1.12); p=0.135                   0.63 (0.35, 1.13); 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% CI)  0.85 (0.45, 1.61); p=0.610                   0.76 (0.34, 1.72); 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% CI)  0.79 (0.38, 1.67); p=0.544                   0.65 (0.26, 1.64); 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 £25 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 (mailto: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 (mailto: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
 Uninfected                     No clinical or virological evidence of infection              0
 Ambulatory                     No limitation of activities                                   1
                                Limitation of activities                                      2
 Hospitalized - Mild disease    Hospitalized, no oxygen therapy                               3
                                Oxygen by mask or nasal prongs                                4
 Hospitalized - Severe disease  Non-invasive ventilation 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 (http://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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