Clinical Trial Finds Inhaled Immune Response Protein Increases Chances of Recovery for Hospitalized COVID-19 Patients

COVID-19 patients hospitalized in the UK who received an inhaled form of interferon beta-1a (SNG001) were more likely to recover and less likely to develop severe symptoms than patients who received a placebo, according to a new published clinical study. up The Lancet Respiratory Medicine magazine. This is the first evidence published in a peer-reviewed medical journal that inhaled interferon beta-1a could reduce the clinical consequences of COVID-19 and serves as proof of the concept that this treatment could help hospitalized patients recover, but are needed. further research .

As the number of COVID-19 infections continues to rise around the world, there is an urgent need to develop new treatments for more severe and life-threatening symptoms such as pneumonia and respiratory failure.

Interferon beta is a naturally occurring protein that coordinates the body’s immune response to viral infections. Laboratory studies have found that the SARS CoV-2 virus directly suppresses the release of interferon beta, while clinical studies demonstrate a reduced activity of this important protein in COVID-19 patients. The formulation of interferon beta used in this new study – SNG001 – is administered directly to the lungs via inhalation and has been tested in the treatment of asthma and chronic obstructive pulmonary disease (COPD). This study aimed to evaluate the safety and efficacy of SNG001 for the treatment of hospitalized COVID-19 patients.

The study was conducted in nine UK hospitals with patients who had a confirmed SARS-CoV-2 infection. It compared the effects of SNG001 and placebo given to patients once daily for up to 14 days and followed up patients for up to 28 days after starting treatment. Patients were recruited from March 30 to May 30, 2020 and were randomly assigned to receive treatment or a placebo. All members of the research group were blinded to which group the patients were assigned. During the study, changes in the patients’ clinical conditions were monitored.

Of the 101 patients enrolled in the study, 98 patients received treatment in the study (three patients withdrew from the study) – 48 received SNG001 and 50 received a placebo. At the start of the study 66 (67%) patients required oxygen supplementation at baseline (29 people in the placebo group and 37 in the SNG001 group). Patients who received SNG001 were twice as likely to show improvement in their clinical condition on day 15 or 16 compared to the placebo group.

In the placebo group, 11 (22%) of the 50 patients developed severe disease (defined in this study as requiring mechanical ventilation) or died between the first dose and day 15 or 16, compared with six (13%) of the 48 patients who received SNG001 (this includes three deaths in the placebo groups and none in the treatment group).

During the 14-day treatment period, patients who received SNG001 were more than twice as likely to recover as those in the placebo group, with 21 (44%) patients in the SNG001 group recovering versus 11 (22%) patients in the placebo group (patients were thought to have recovered when they were no longer restricted in their activity). In a secondary analysis, the authors found that at 28 days, SNG001 patients were three times more likely to recover than patients receiving placebo.

Lead author, Professor Tom Wilkinson of the University of Southampton, UK, says: “The results confirm our belief that interferon beta, a widely known drug approved for use in its injectable form for other indications. , may have the potential as an inhaled drug to restore lung immune response and accelerate recovery from COVID-19. Inhaled interferon beta-1a provides high, local concentrations of the immune protein, which increases lung defenses rather than targeting specific viral mechanisms. This could bring additional benefits in treating COVID-19 infection when it occurs alongside an infection from another respiratory virus, such as influenza or respiratory syncytial virus (RSV) which can be found in months winter “.

The safety of inhaled interferon beta-1a was assessed by monitoring for adverse events over 28 days. 26 (54%) patients in the SNG001 group and 30 (60%) patients in the placebo group experienced adverse events during treatment, with the most frequently reported headache. Fewer patients in the SNG001 group experienced serious adverse events, compared with the placebo group.

The authors note some limitations of their study. The sample size was small and, as such, the results cannot be generalized to larger populations and health care facilities. There were differences between the two groups at recruitment: patients in the SNG001 group had more severe disease at baseline and more patients had hypertension, and in the placebo group more patients had diabetes and cardiovascular disease. However, these factors were considered in the statistical model used and the beneficial signals for therapy were improved when a priori adjustments were made. According to the researchers, larger studies should be able to address these limitations by randomizing more diverse groups.

The same research group is also evaluating the effectiveness of treatment in pre-hospital cases of COVID-19. To evaluate treatment for patients who are critically ill and require mechanical ventilation, an alternative method of administration to the current nebulizer is required.

Writing in a related comment, lead author Nathan Peiffer-Smadja (who was not involved in the study), of Assistance Publique – Hôpitaux de Paris, France, pointed out that the preliminary results of the SOLIDARITY / DisCoVeRy randomized clinical trial in COVID patients -19 (which includes 8% who were mechanically ventilated) has so far failed to demonstrate the efficacy of subcutaneous injectable interferon beta-1a. One possible explanation is because this route of administration does not provide the targeted delivery of the drug to the lungs, which occurs with inhaled delivery. The comment also highlights concerns that in patients with severe COVID-19 use of the drug could increase inflammatory response and be associated with safety concerns.

He says: “The number of patients enrolled in this pilot clinical trial is obviously small. Furthermore, this study did not show any impact of the evaluated treatment on time to discharge or mortality, although the study obviously could not respond to the second. Question. Larger randomized clinical trials are therefore needed to confirm these findings. The safety of nebulized interferon beta-1a will be of particular concern as nebulization of the interferon does not yet have a marketing authorization for any indication. studies should aim to evaluate the effect of interferon beta-1a on inflammatory biomarkers and virological data to better characterize the pathophysiology underlying the use of this drug. It will also be interesting to investigate whether there is an impact of interferon beta-1a on prolonged symptoms, especially pulmonary “.