COVID-19

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.

COVID-19 – SG016 Clinical Trial Data Readout

On 20 July 2020, Synairgen announced positive results from its Phase II double-blind placebo-controlled trial, called SG016, in hospitalised COVID-19 patients. 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 on day 16 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=0.017) 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.

Synairgen’s Phase II trial in COVID-19 patients, called SG016 (EudraCT: 2020-001023-14), is a double-blind, placebo-controlled trial. The 221 patient trial comprises 101 patients initiated in hospital and 120 patients to be initiated in the home setting. The patients participating in the hospital setting, which completed recruitment in May, have been recruited across a number of NHS trusts and the trial has been 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.

Peer-reviewed data from the trial was published in The Lancet Respiratory Medicine journal on 12 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.’

IFN-β 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 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.

In the lab IFN-beta has been shown to protect cells from 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 SNG001 has been well tolerated and shown to upregulate lung antiviral defences. In two Phase II trials in asthma, inhaled SNG001 improved lung function in patients with a cold or flu infection. A trial in COPD is ongoing. Early data has shown that the drug is well tolerated and upregulates lung antiviral defences in COPD.

Figure 1. SNG001 reduced viral load following MERS-CoV infection in cell-based assays with a similar potency to that seen against other respiratory viruses

SG016 Home Study Trial

For patients interested in participating in the SG016 home trial, please see the following link for more information:

www.covidtrialathome.com

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 formulation of interferon beta (IFN-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)1283494340 or emailing medicineaccess@clinigengroup.com.

Patients seeking information should contact their physician.

Phase III trial (SG018)

Synairgen intends to commence a Phase III randomised placebo-controlled trial of SNG001 in hospitalised COVID-19 patients, named SG018, with an anticipated start date during Q4 2020.

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