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

Hospitalized COVID-19 patients 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 trial in Lancet respiratory medicine diary. This is the first evidence published in a peer-reviewed medical journal that inhalation of interferon beta-1a could lessen the clinical consequences of COVID-19 and serves as proof of concept that this treatment could help hospitalized patients recover, but more research is required. .

As the number of COVID-19 infections continues to rise around the world, there is a pressing need to develop new treatments for the most serious and life-threatening symptoms, such as pneumonia and respiratory failure.

Interferon beta is a natural 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 trials demonstrate decreased activity of this important protein in COVID-19 patients. The interferon beta formulation used in this new study, SNG001, is administered directly to the lungs by 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 in treating hospitalized patients with COVID-19.

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

Of the 101 patients enrolled in the study, 98 patients received the treatment in the trial (three patients withdrew from the trial): 48 received SNG001 and 50 received a placebo. At the start of the trial, 66 (67%) patients required oxygen supplementation at the start of the study (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 status on day 15 or 16, compared to the placebo group.

In the placebo group, 11 (22%) of 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 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 receiving SNG001 were more than twice as likely to recover, compared to those in the placebo group, with 21 (44%) patients in the SNG001 group recovering compared to 11 (22%). ) patients in the placebo group (patients were considered to have recovered when they were no longer limited in their activity). In a secondary analysis, the authors found that at 28 days, patients with SNG001 were three times more likely to recover than patients who received placebo.

Lead author Professor Tom Wilkinson from 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 the lung’s immune response and accelerate recovery from COVID-19. Inhaled interferon beta-1a provides high local concentrations of immune protein, which strengthen lung defenses rather than attack specific viral mechanisms. This it could have additional benefits in treating COVID-19 infection when it occurs in conjunction with infection with another respiratory virus, such as influenza or respiratory syncytial virus (RSV) that can well be found in the winter months. “

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

The authors point out some limitations of their study. The sample size was small, and as such the findings cannot be generalized to broader populations and healthcare settings. There were differences between the two groups at the time of 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 beneficial signals for therapy improved when a priori adjustments were made. Larger trials should be able to address these limitations with the randomisation of more varied groups, according to the researchers.

The same research group is also evaluating the effectiveness of treatment in pre-hospital cases of COVID-19. To evaluate the management of critically ill patients requiring mechanical ventilation, an alternative delivery method to the current nebulizer is needed.

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

He says: “The number of patients enrolled in this pilot clinical trial is, of course, small. Furthermore, this study did not show any impact of the assessed treatment on time to discharge or mortality, although the study obviously did not have the power to answer the last question. Therefore, larger randomized clinical trials are needed to confirm these results. The safety of nebulized interferon beta-1a will be of special interest as interferon nebulization is not yet licensed for any indication. These trials 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 study whether there is an impact of interferon beta-1a on prolonged symptoms , especially pulmonary “.