Interferon Alpha Nasal Spray Decreases COVID-19 Risk in Those With Cancer

Only 2 patients died in the phase 3 trial evaluating interferon-alpha in adult patients with cancer, but were deemed unrelated to study treatment.

Daily use of interferon-alpha (IFN-α) as a nasal spray was found to reduce the incidence of COVID-19 for adult patients with cancer, according to results from a phase 3 trial (NCT04534725) published in Clinical Infectious Diseases.

In the intention-to-treat (ITT) population, the overall incidence of COVID-19 infection was 11.3% in the IFN-α arm. There was a lower incidence of infection in the IFN-α arm of 8.3% vs 14.4% in the placebo arm (relative risk [RR], .60; 95% credible intervals [CrI], .33-.97). These results showed a 40% reduction in the risk of infection for the IFN-α arm. Additionally, the cumulative incidence of COVID-19 was lower in the IFN-α arm compared with the placebo arm (HR, .55; 95% CI, .32-.97; P = .04).

“IFN-α nasal spray reduced the incidence of COVID-19 and, in particular, in those younger than 65 years and female. It may be that, during the study period, being younger and female was a marker of high risk with working and caring responsibilities and thus higher community exposure to COVID-19. We did not see any differences in the subgroup aged 65 years and older, which is recognized as having a higher risk of progression to severe disease,” Michelle K. Yong, MBBS, FRACP, MPH, PhD, and co-authors of the study wrote in the publication. “Patients receiving IFN-α nasal spray who received a COVID-19 vaccination had a reduced risk of COVID-19 infection by 50%. COVID-19 vaccines were considered standard of care. We did not find any differences in COVID-19 incidence based on cancer type or whether patients were receiving active cancer-related treatment.”

IFN-α was evaluated at a 40,000 IU dose per day because of previously available literature. Patients were given a reformulation of IFN-α-2a/β as a nasal spray and delivered at 20,000 IU/mL per 100 μL actuation. IFN-α was dispensed at either 40,000 IU a day or a normal saline nasal spray.Patients were given a self-testing kit with a nasal swab, viral medium, a prepaid envelope, a symptom diary, and instructions regarding how to perform self-testing when influenza symptoms developed.

Patients were required to have visits at 30, 60, and 90 days, which marked the end of treatment, with the option of study follow-up of 120 and 365 days. During the study, investigators assessed for influenza-like illness symptoms, adherence, and adverse effects (AEs).

The primary end points were incidence of COVID-19 and/or other respiratory viruses within 90 days of randomization.

A total of 433 patients were enrolled in the trial and randomly assigned to either the IFN-α arm (n = 217) or the placebo arm (n = 216). The median patient age in the IFN-α arm was 62 years old, 51% were female, and 91% were White. The primary cancers were hematologic (48%) or solid tumors (52%). The per-protocol analysis included 389 patients.

In the per-protocol cohort, the overall incidence of COVID-19 was 11.8%. In the IFN-α arm, a lower incidence of COVID-19 was observed with 7.7% of patient’s vs 16% in the placebo arm (RR, 0.50; 95% CrI, .26-.84). The incidence of other respiratory events was 4.6% vs 5.7%. Between arm, the cumulative incidence of COVID-19 was lower in the IFN-α arm vs placebo (HR, .46; 95% CI, .26-.82; P = .008).

The trial was stopped early, but a post-hoc analysis showed the trial had a 95.1% power with a 5% alpha error rate to find the true result.

The subgroup analysis showed that those in the IFN-α arm had a decreased risk of infection if they were younger than 65 (RR, .48; 95% CrI, .20-.92), were female (RR, .44; 95% CrI, .19-.85), or had received a COVID-19 vaccine (RR, .50; 95% CrI, .26-.82) compared with the placebo arm. The per-protocol population arm showed a decrease in infection risk for those with solid tumors (RR, .39; 95% CrI, .14-.82), those who were younger than 65 (RR, .36; 95% CrI, .13-.71), those who were female (RR, .36; 95% CrI, .13-.71), and those who had a COVID-19 vaccine (RR, .49; 95% CrI, .25-.83).

Regarding safety, 10.1% of patients in the IFN-α arm had AEs vs 6.0% in the placebo arm (RR, .56; 95% CrI, .16-1.33). Serious AEs were noted in 4.1% vs 2.8% (RR, 1.23; 95% CrI, .36-3.12), while AEs of special interest of grade 2 were observed in 0.5% vs 0.5%, with similar rates for all-cause mortality.

During the study period, one patient in each arm died, but were deemed unrelated to the intervention treatment.

Reference

Yong MK, Thursky K, Crane M, et al. Interferon-α nasal spray prophylaxis reduces COVID-19 in cancer patients: a randomized, double-blinded, placebo-controlled trial. Clin Infect Dis. Published online August 28, 2025. doi:10.1093/cid/ciaf409