COVID-19

NEWS

Background

Coronaviruses cause respiratory infections ranging from the common cold to more severe diseases such as Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). The most recently discovered coronavirus (SARS-CoV-2) causes coronavirus disease COVID-19.

COVID-19 is a global threat and there is an urgent need to assess new treatments to prevent and effectively treat the severe lower respiratory tract (LRT) illness that occurs in around 1 out of 6 people with this disease.* Older people and those with co-morbidities such as heart and lung complications, or diabetes are at greatest risk of developing severe or fatal disease.*

SNG001 therefore could prove to have an important role to play in outbreaks such as the current COVID-19 epidemic, particularly in at risk groups that develop severe LRT viral illness.

Interferon beta for the treatment of COVID-19

  • Interferon beta (IFN-beta) is a naturally-occurring protein, which orchestrates the body's antiviral responses. There is evidence that the deficiency in IFN-beta production by the lung could explain the enhanced susceptibility of these at-risk patient groups to developing severe lung disease during respiratory viral infections. Furthermore, viruses, including coronaviruses, have evolved mechanisms which suppress endogenous IFN-beta production, thereby helping the virus evade the innate immune system. IFN-beta is a safe, well tolerated medicine, which is already used in numerous approved multiple sclerosis drugs.
  • In the laboratory, IFN-beta has been shown to protect cells form infection with a broad range of respiratory viruses that cause LRT illness including highly pathogenic coronavirus strains, including MERS-CoV (Figure 1 below), SARS-CoV and SARS-CoV-2**, the virus which causes COVID-19.
  • Synairgen is developing a formulation of IFN-beta, called SNG001, for direct delivery to the lungs via nebulisation, to treat and/or prevent LRT illness caused by respiratory viruses.
  • In clinical trials in asthma and COPD, inhaled interferon beta (SNG001) has been well tolerated and shown to upregulate lung antiviral defences. In two Phase II trials in asthma and one study in COPD, SNG001 improved lung function in patients with a cold or flu infection.

SG016 Hospital Cohort Data Readout

On 20 July 2020, Synairgen announced positive results from its Phase II double-blind placebo-controlled trial of inhaled interferon beta, SNG001, in hospitalised COVID-19 patients.

The trial, called SG016 (EudraCT: 2020-001023-14), was a double-blind, placebo-controlled trial. The 221 patient trial comprised 101 patients initiated in hospital and 120 patients initiated in the home setting. The patients who participated in the hospital setting, were recruited across a number of NHS trusts and the trial was adopted by the NIHR Respiratory Translational Research Collaboration which is comprised of leading centres in respiratory medicine in the UK whose internationally recognised experts are working together to accelerate development and discovery for COVID-19.

The primary endpoint was the change in condition assessed using the WHO Ordinal Scale for Clinical Improvement (OSCI) during the dosing period. More detailed results of primary endpoint analyses were disclosed in Synairgen’s 2020 Interim Results on 29 September 2020, which can be read here.

Key findings included

The odds of improvement across the entire OSCI scale were more than two-fold greater in the SNG001 group than the placebo group at the end of treatment in both the ITT (Intention-To-Treat) population (OR 2.32; p=0.033) and the PP (Per Protocol) population (OR 2.80; p=0.017).

There was a trend towards reduced odds of progression to severe disease (requiring non-invasive ventilation, high-flow oxygen, intubation and mechanical ventilation) or death in the ITT population (72% reduction; p=0.064) that became significant in the PP population (82% reduction; p=0.041).

Patients who received SNG001 were more than twice as likely to recover (defined as ‘no limitation of activities’ or ‘no clinical or virological evidence of infection’) over the course of the treatment period compared to those receiving placebo in both the ITT population (HR 2.19; p=0.043) and the PP population (HR 2.29; p=0.033).

Over the treatment period, patient-reported Breathlessness Cough and Sputum Scale (BCSS) and in particular breathlessness scores were markedly reduced in patients who received SNG001 compared to those receiving placebo (p=0.026 for BCSS and p=0.007 for breathlessness).

Three subjects (6%) died after being randomised to placebo. There were no deaths among subjects treated with SNG001.

Interestingly, the efficacy analyses indicate there is no evidence of an association between the SNG001 positive treatment effects and prior duration of COVID-19 symptoms.

Peer-reviewed data from the trial was published in The Lancet Respiratory Medicine journal on 13th November 2020. The full title of the publication is: “Safety and efficacy of inhaled nebulised interferon beta-1a (SNG001) for treatment of SARS-CoV-2 infection: a randomised, double-blind, placebo-controlled, phase 2 trial”, and can be accessed here.

SG016 Home Cohort Data Readout

On 30 April 2021, Synairgen announced results from the Home Cohort of its SG016 Phase II trial of SNG001 in SARS-CoV-2 infected patients and data from the combined analysis of the Hospital and Home Cohorts. 

The Home Cohort of the trial arm comprised 120 ‘at risk’ (aged over 65 or over 50 with a risk factor) patients in the home setting to investigate if SNG001 could prevent development of severe LRT illness.

Home Cohort key findings

In total, only two patients were admitted to hospital due to worsening of COVID-19 during the treatment period, both from the placebo group. The hospitalisation rate (approximately 3% in the placebo group) in this ‘at risk’ COVID-19 patient population was lower than had been originally anticipated, but is in line with other recent large peer-reviewed therapeutic studies.*** Consequently, the prevention of severe LRT illness could not be determined. The majority of patients exhibited only mild disease which we believe compromised the possibility of showing treatment effects in the Home Cohort. We therefore decided to analyse the subset of patients with most severe symptoms.

A post hoc analysis was conducted focusing on the 12% of patients who had significant breathlessness (marked or severe, as defined by the Breathlessness scoring system from the Breathlessness, Cough and Sputum Scale) at the time treatment began. In these patients, the recovery to level 1 on the OSCI (‘no limitation of activities’) followed a similar pattern to that observed previously in the hospital population where SNG001 accelerated recovery.

A further finding from the Home Trial arm of SG016 was that patients can successfully initiate treatment “remotely”, self-administering SNG001 at home without the need for a face-to-face meeting with a health care professional, reducing the burden on hospital facilities and minimising the risk of onward infection.

Combined Hospital and Home Cohorts data

A combined analysis of the Hospital and Home Cohorts data was conducted to explore the impact of the different levels of breathlessness, which is one of the most prominent symptoms of COVID-19, on time to recovery.

  • An assessment of placebo patients only indicated that those with marked or severe breathlessness at time of treatment initiation had slower recovery to no limitation of activities than those patients who were not as breathless.
  • In the Hospital Cohort (reported in July 2020) patients were 2.19 times more likely to recover to level 1 on the Ordinal Scale compared to placebo, HR 2.19, p=0.043. The addition of the 12 markedly and severely breathless Home Cohort patients changes the Hazard Ratio to 2.49, p=0.009.
  • Interestingly, not all hospitalised patients were markedly or severely breathless at time of treatment initiation. An analysis including only patients who were markedly or severely breathless at the time of treatment initiation, irrespective of whether they were in hospital or at home, showed that those treated with SNG001 (n=33) were 3.41 times more likely to recover than those on placebo (n=36) (HR 3.41 [95% confidence interval 1.47- 7.94], p=0.004).

Antiviral activity of SNG001 against SARS-CoV-2 variants

On 24 May 2021, Synairgen announced results of in vitro trials that were conducted to test the antiviral activity of SNG001 against the B.1.1.7 ("UK" or "Kent") and B.1.351 ("South African") variants.

In these experiments, Vero E6 cells were treated with SNG001 prior to and after infection with SARS-CoV-2. 16-24 hours after infection, the presence of SARS-CoV-2 viral proteins was determined using an immunostaining method.

SNG001 potently reduced virus to undetectable levels in cells infected with "Wuhan-like" (virus strain: Germany/BavPat1/2020), the UK/Kent variant and the South African variant. These data show both SNG001's potency against SARS-CoV-2 variants and confirm its broad-spectrum antiviral activity.

Managed Access Program

In September 2020, Synairgen plc signed an agreement with Clinigen Group plc (AIM: CLIN, ‘Clinigen’), the global pharmaceutical and services company, to launch a Managed Access Program for Synairgen’s inhaled interferon beta, SNG001, in the UK and the EU for the treatment of hospitalised COVID-19 patients.

Healthcare professionals in the EU can obtain details about the SNG001 Managed Access Program by calling the customer service team at +44(0)1283 494340 or emailing medicineaccess@clinigengroup.com.

Patients seeking information should contact their physician.

Phase III trial (SG018)

Synairgen has commenced a Phase III randomised placebo-controlled trial of SNG001 in hospitalised COVID-19 patients, named SG018. The trial is a randomised, placebo-controlled study being conducted in 17 countries and has completed recruitment of 610 COVID-19 patients. Synairgen is on track to share top line results in early 2022.

References

  1. * Sourced from WHO website 15th Mar 20
  2. ** Mantlo E, Bukreyeva N, Maruyama J, Paessler S, Huang C. Antiviral activities of type I interferons to SARS-CoV-2 infection. Antiviral Res. 2020 Apr 29;179:104811
  3. *** https://investor.regeneron.com/news-releases/news-release-details/phase-3-trial-shows-regen-covtm-casirivimab-imdevimab-antibody’

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