Inhaled IFN-β1a shows favourable signals for hospitalized COVID-19 patients

In the phase III SPRINTER trial, inhaled interferon-beta-1a (IFN-β1a) showed encouraging signals for preventing disease progression or death in hospitalized COVID-19 patients.

“[Our] study did not meet its primary efficacy endpoint looking at hospital discharge/recovery (potentially due to changes in standard of care [SoC]),” said Professor Tom Wilkinson from the University of Southampton, UK, at ERS 2022. There was no clinical signal of efficacy with inhaled IFN-β1a vs placebo in terms of the probability of hospital discharge (hazard ratio, 1.06; p=0.51).

However, Wilkinson underlined trends favouring inhaled IFN-β1a over placebo in terms of the prevention of progression to severe disease or death, albeit lacking statistical significance (relative risk reduction [RRR], 26 percent; odds ratio [OR], 0.71; p=0.16).

These were further supported by post hoc results evaluating patients with O₂ saturation ≤92 percent or respiratory rate ≥21 breaths/minute. In this subgroup, the risk of progressing to severe disease or death was reduced by 44 percent (p=0.08). “[Of note, these were] patients who had severe respiratory disease, were more hypoxic, and had high respiratory rate,” noted Wilkinson.

Despite a separation of effect between arms in terms of the other two key secondary endpoints, the differences were not statistically significant (RRR, 12 percent; OR, 0.85; p=0.61 [progression to intubation or death within 35 days] and RRR, 16 percent; OR, 0.79; p=0.54 [death within 35 days]).

Compared with the placebo arm, the inhaled IFN-β1a arm had a similar rate of any treatment-related treatment-emergent adverse events (TEAEs; 23 percent vs 25 percent) but lower incidence of any serious TEAEs (13 percent vs 18 percent) and pulmonary emboli (n=0 vs 5). “Inhaled IFN-β1a was generally well-tolerated [among] hospitalized COVID-19 patients, which is in line with previous clinical trial results on COVID-19, asthma, and COPD*,” said Wilkinson.

Built on positive phase II outcomes

SPRINTER evaluated 623 hospitalized (non-ICU) COVID-19 patients (mean age 52 years, 66 percent female) requiring supplemental low-flow** oxygen therapy. Of these, 18 percent were fully vaccinated against COVID-19 and roughly 90 percent received systemic corticosteroids for COVID-19. Participants were randomized 1:1 to receive inhaled IFN-β1a or placebo QD for 14 days on top of SoC.

SPRINTER was built on a phase II study that showed a range of positive outcomes with inhaled IFN-β1a against COVID-19. [Lancet Respir Med 2021;9:196-206] “We saw a very positive signal of clinical benefit in a disease form that, [considering the context of the disease in its early days,] had a very aggressive trajectory and a lot of severe [hospitalizations],” Wilkinson noted.

Apart from the reduced likelihood of developing severe disease or death and faster times to recovery and hospital discharge with inhaled IFN-β1a in the phase II trial, recovery occurred fairly early on in the disease course (ie, within a day or two of treatment), Wilkinson stressed. “This was an important finding.”

A useful treatment alternative

“IFN-β is important … in the innate response to respiratory viral infections. It is … produced in abundance in the acute phase of infection,” explained Wilkinson. “Importantly, in COVID-19, not only were patients unable to mount an appropriate IFN response, [but] it has been clearly identified earlier in the pandemic [that the disease] is likely to have poor outcomes.”

“If the encouraging signal in the relative risk of disease progression or death in this trial was confirmed in a larger trial, inhaled IFN-β1a could become a useful treatment option for hospitalized COVID-19 patients,” he continued. “[The] inhaled delivery approach gives maximum biological availability of the drug to the site of interest … and limits systemic exposure.”

Wilkinson shared that they are now looking at further analysis of the current data to take on the drug potentially for use in a wider viral setting and in a selected COVID-19 population.