With a more direct mechanism of action against viral replication compared with standard treatments, the small interfering RNA (siRNA)-based MIR 19 treatment could revolutionize outpatient COVID-19 treatment.
MIR 19 (siR-7-EM/KK-46), a small interfering RNA (siRNA) inhaled treatment targeting SARS-CoV-2—the virus that causes COVID-19—was found to meaningfully decrease the progression to moderate or severe disease in outpatients with mild COVID-19 while being well tolerated, according to the results of an open-label, randomized, controlled multicenter phase 2b-3 clinical trial (NCT05783206) published in Allergy.1,2
As COVID-19 remains a dangerous public health threat, continued investigations into novel treatment methods are critical. RNA interference (RNAi) may offer a meaningful tool for inhibiting specific areas of viral replication, targeting respiratory conditions such as COVID-19.3
A previously conducted open-label, randomized, multicenter phase 2 trial (NCT05184127) from the same group of investigators as the current study compared low and high doses of MIR 19 with standard etiotropic drug treatment in patients hospitalized with moderate COVID-19. Patients receiving a low dose of MIR 19 (3.7 mg/d) successfully reached the primary end point, which was defined as the simultaneous achievement of fever relief, normalization of respiratory rate, coughing reduction, and sufficient oxygen saturation. The end point was reached significantly earlier compared with those receiving standard care.3,4
Furthermore, patients in the phase 2 trial did not experience any adverse events (AEs) directly associated with MIR 19, which is an important development. The investigators determined that the formulation was safe and effectively reduced time to clinical improvement in patients. Following these positive phase 2 trial results, the investigators initiated the current phase 2b-3 study to further evaluate the safety and efficacy of MIR 19, this time with a new dose of 5.5 mg/d and a larger patient population.1,3
A population of 492 outpatients with mild COVID-19 was evaluated in each group of this phase 2b-3 clinical trial, which compared those receiving inhaled MIR 19 to those receiving standard care. The primary study end point was the proportion of patients who were found to develop moderate or severe COVID-19 by day 28 of randomization, according to the study authors.1
Trial Name: Evaluation of Safety & Efficacy of MIR 19 ® Inhalation Solution in Patients With Mild COVID-19
ClinicalTrials.gov ID: NCT05184127
Sponsor: National Research Center - Institute of Immunology Federal Medical-Biological Agency of Russia
Completion Date: July 28, 2023
The investigators detected a moderate or severe course of the disease in 14 (2.85%) and 34 (6.91%) patients in the 5.55-mg MIR 19 and standard therapy groups, respectively, with a difference in proportions of -4.107% (95% CI, -7.28% to -1.03%; P = .002). AEs were only reported in 77 (15.65%) and 100 (20.33%) patients in the respective groups. Importantly, there were no severe, treatment-related AEs observed in the MIR 19-treated group, providing bolstered indications of the treatment’s efficacy and safety.1
These results are like those garnered in the previously conducted phase 2 study. A critical area of MIR 19 that must be fleshed out is the proper dosage for patients to receive the best possible outcome. In the phase 2 trial, patients who received a higher dose of MIR 19 (11.1 mg/d) did not experience any statistically significant therapeutic effects. Based on the positive results stemming from a 5.55-mg/d dose of MIR 19, future investigations are poised to continue adjusting the dose of MIR 19 to achieve the strongest therapeutic outcomes in patients with COVID-19.1,3
