Hospitalized COVID-19 patients receiving SNG001, inhaled nebulized interferon beta-1a, were more likely to show clinical improvement than those receiving placebo, a small pilot study in the U.K. found.
Patients randomized to receive SNG001 for 14 days had greater odds of improvement on the World Health Organization (WHO) ordinal scale for clinical improvement (OSCI; OR 2.32, 95% CI 1.07-5.04, P=0.033) on day 15 or 16 compared with those receiving placebo, reported Tom Wilkinson, PhD, of University of Southampton in England, and colleagues.
Moreover, patients in the intervention group were more likely to revert to an OSCI score of 1, or no limitation of activities, on day 15 or 16 (HR 2.19, 95% CI 1.03-4.69, P=0.043), the authors wrote in the Lancet Respiratory Medicine.
Type 1 interferon is “one of the first cytokines induced by viral infection of a cell and is a primary driver of innate immune responses in the human lung,” the researchers noted. They explained that SNG001 is a formulation of recombinant interferon beta “for inhaled delivery by [nebulizer],” which has been well tolerated in clinical studies among patients with asthma or chronic obstructive pulmonary disease.
Interestingly, an accompanying editorial by Nathan Peiffer-Smadja, MD, and Yazdan Yazdanpanah, MD, PhD, both of Assistance-Publique Hôpitaux de Paris in France, noted that interferon failed in preliminary results from the WHO’s SOLIDARITY trial.
In addition to different composition of the two trials, the editorialists found another key difference: route of administration. SOLIDARITY used subcutaneous interferon beta-1a, whereas this trial used nebulized therapy that “delivers interferon beta-1a directly to the respiratory tract.”
“[Nebulized] therapy allows targeted delivery of interferon to the lungs, where it can induce the expression of interferon-stimulated genes that participate directly … or indirectly … in the antiviral response in the mucosa,” Peiffer-Smadja and Yazdanpanah wrote.
For the new study, Wilkinson and colleagues randomized adults hospitalized with COVID-19 symptoms, who tested positive for SARS-CoV-2 via reverse-transcriptase polymerase chain reaction or point-of-care test to receive either SNG001 or inhaled placebo for 14 days. Primary outcome was change in clinical condition on the WHO OSCI (a 9-point scale where 0 means no infection and 8 means death).
From March 30 to May 30, a total of 48 patients were randomized to SNG001 and 50 to placebo in an intent-to-treat analysis. Patients were a mean age of 57, 59% were men, and 80% were white. Baseline comorbidities included hypertension, cardiovascular disease, diabetes, chronic lung condition, and cancer.
Demographic characteristics between groups were similar, although the SNG001 group had more severe disease, with 77% of patients receiving oxygen therapy vs 58% in the placebo group. Mean duration of symptoms before treatment initiation was 10 days.
In the SNG001 group, the odds of improvement were more than three-fold greater on day 28 versus placebo (OR 3.15, 95% CI 1.39-7.14, P=0.046), the authors noted.
Five patients underwent intubation or died compared with three in the intervention group. Over the 14 days of treatment, patients in the intervention group were more than twice as likely to recover.
There was no difference in the odds of hospital discharge or time to hospital discharge between groups. By day 14, 73% of the placebo group and 69% of the intervention group had been discharged.
Regarding safety, 54% of patients in the intervention group and 60% in the placebo group reported treatment-emergent adverse events, the most common of which was headache (15% and 10%, respectively). Fewer patients in the intervention group had serious adverse events compared with placebo (15% vs 28%), and the most common were respiratory failure (6% vs 12%) and pneumonia (6% each).
One patient in the placebo group had multiple organ dysfunction syndrome and one had pulmonary embolism, which caused them to withdraw from the study. These patients later died, along with a third patient in the placebo group, who died of COVID-19 pneumonia.
In their editorial, Peiffer-Smadja and Yazdanpanah noted that the study was not powered to assess mortality outcomes, and called for large randomized trials to investigate the effectiveness of nebulized interferon beta-1a, speculating that it might benefit patients in an early stage of disease in the outpatient setting.
“In patients with severe COVID-19, an exacerbated inflammatory response has been identified as a cause of pulmonary complications, and interferon beta-1a — a pro-inflammatory cytokine — could increase the inflammatory response and be associated with safety issues,” the editorialists wrote.
They added that safety will also be a concern, as “[nebulization] of interferon has no marketing [authorization] for any indication yet.”
Notably, COVID-19 guidelines from the National Institutes of Health recommend against the use of interferon, except within a randomized clinical trial.