Inhaled interferon falls short for COVID-19 discharge, recovery but hints of other benefits: SPRINTER

SAN FRANCISCO — Treatment with inhaled interferon beta failed to improve discharge and recovery in patients hospitalized with moderate COVID-19, according to results of the phase 3 SPRINTER trial.

“While the study did not meet its primary efficacy endpoints looking at hospital discharge and recovery, potentially due to changes in standard of care, there were trends in favor of SNG001 in prevention of progression to severe disease or death,” Phillip Monk, PhD, chief scientific officer of Synairgen, said during a presentation at the American Thoracic Society International Conference.

The SPRINTER trial evaluated efficacy and safety of an investigational formulation for inhalation containing the broad-spectrum antiviral protein interferon beta (SNG001, Synairgen) for the treatment of adults hospitalized due to COVID-19 who required supplemental oxygen.

A total of 623 patients were randomly assigned to interferon beta or placebo delivered by Aerogen Solo/Ultra vibrating mesh nebulizer with a filter on the exhalation port once daily for up to 14 days on top of standard of care.

The primary endpoint of SPRINTER was time to hospital discharge and time to recovery to no limitation of activities up to day 28.

There was no difference between treatment groups for the primary endpoint of time to hospital discharge (HR = 1.06; 95% CI, 0.89-1.27; P = .509), Monk said during the presentation. When the researchers evaluated time to recovery, there was also no difference.

“This was surprising based on the promising data from the phase 2 trial,” Monk said. Phase 2 data from both the home and hospital settings demonstrated patients who received inhaled interferon beta were more than twice as likely to recover over the treatment period compared with those who received placebo, with trends toward progression of severe disease and death, he said.

Monk said the lack of difference between treatments is likely due to improved standard of care during the pandemic, which also changed hospital practice because patients are doing better.

There was an encouraging signal in reduction in the RR of progression to severe disease or death within 35 days, with a 25.7% reduction with inhaled interferon beta in the intention-to-treat population and 36.3% reduction in the per-protocol population, according to the results. In addition, there was an 11.6% RR reduction with inhaled interferon beta in progression to intubation or death within 35 days in the intention-to-treat population and a 32% RR reduction in the per-protocol population, and a 16.3% RR reduction in death within 35 days in the intention-to-treat population and a 40.5% RR reduction in the per-protocol population.

To assess the strength of this signal and identify specific patient populations that might benefit most from treatment, the researchers performed post hoc analyses on groups of patients at greater risk for developing severe disease, including those aged 65 years and older, those with comorbidities associated with worse COVID-19 outcomes and those who had clinical signs of compromised respiratory function despite receiving low-flow oxygen at baseline. In the post hoc analyses, inhaled interferon beta had stronger treatment effects, with the strongest effect observed in those who had clinical signs of compromised respiratory function. In these patients, who represented approximately one-third of the entire population, inhaled interferon beta significantly reduced the risk for progression to severe disease and death compared with placebo by 70% in the per-protocol population (OR = 0.23; 95% CI, 0.06-0.98; P = .046), according to information in a press release.

“Subgroup analyses increase confidence that SNG001 is having a beneficial effect with respect to prevention of severe disease or death, with enhanced trends in favor of SNG001 in subgroups enriched for disease severity and/or risk factors for disease progression,” Monk said during the presentation.

Inhaled interferon beta was well tolerated in the SPRINTER trial, with a favorable safety profile that was consistent with that observed in previous studies, according to the researchers. The proportion of patients with any treatment-emergent adverse events related to study treatment was 22.6% for inhaled interferon beta vs. 25.4% for placebo; any serious treatment-emergent adverse event was 12.6% vs. 18.2%, respectively; and serious respiratory treatment-emergent adverse event was 4.7% vs. 9.9%, respectively.

The SPRINTER trial was conducted in 17 countries and all patients were randomly assigned from January to November 2021. The mean age was about 52.5 years, two-thirds were men and the majority were white. Median duration of COVID-19 symptoms was 9 days. Nearly three-quarters enrolled had no prior COVID-19 vaccination, while about 18% were fully vaccinated. COVID-19 treatments included systemic corticosteroids in 87% and remdesivir (Veklury, Gilead Sciences) in 18%.

“These clinical results provide a strong clinical rationale to continue to investigate SNG001 in a trial evaluating progression and/or mortality in hospitalized patients with COVID-19 and more widely in patients with severe viral lung infections,” Monk said.

Reference:

• Synairgen presents at ATS 2022. Published May 16, 2022. Accessed May 16, 2022.