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.* To date, according to the WHO, there is no vaccine and no specific antiviral medicine to prevent or treat COVID-19.*

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.

Key findings included

  • The odds of developing severe disease (e.g. requiring ventilation or resulting in death) during the treatment period (day 1 to day 16) were significantly reduced by 79% for patients receiving SNG001 compared to patients who received placebo (OR 0.21 [95% CI 0.04-0.97]; p=0.046).
  • 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 (HR 2.19 [95% CI 1.03-4.69]; p=0.043).
  • Over the treatment period, the measure of breathlessness was markedly reduced in patients who received SNG001 compared to those receiving placebo (p=0.007).
  • Three subjects (6%) died after being randomised to placebo. There were no deaths among subjects treated with SNG001.
  • In the patients with more severe disease at time of admission (i.e. requiring treatment with supplemental oxygen), SNG001 treatment increased the likelihood of hospital discharge during the study, although the difference was not statistically significant (HR 1.72 [95% CI 0.91-3.25]; p=0.096). Median time to discharge was 6 days for patients treated with SNG001 and 9 days for those receiving placebo. Furthermore, patients receiving SNG001 appeared to be more than twice as likely to have recovered by the end of the treatment period (HR 2.60 [95% CI 0.95-7.07]; p=0.062), although this strong trend did not reach statistical significance. However by day 28, patients receiving SNG001 treatment had statistically significantly better odds of recovery (OR 3.86 [95% CI 1.27-11.75]; p=0.017).
  • 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 220 patient trial comprises 100 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.

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

Synairgen’s other current activities with COVID-19

Since the outbreak of COVID-19, Synairgen has been approached by, and is in discussion with, a number of other medical, scientific, and Governmental bodies (both in the UK, US and internationally) seeking to investigate novel therapeutics in this area.

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

www.covidtrialathome.com

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