Fusion Protein Inhibitor for RSV Shows Efficacy in Phase 2 Trial

Both viral load and Wang Respiratory Scores improved after infants aged 1 to 24 months received the oral respiratory syncytial virus (RSV) fusion protein inhibitor AK0529 in a Phase 2 study, according to findings published in Influenza and Other Respiratory Viruses.

RSV causes an estimated 30 million respiratory infections worldwide and primarily affects infants and young children; approximately 3 million young children are admitted to the hospital each year for RSV. Class I viral trimeric fusion is a promising avenue in drug development, and AK0529 is an orally bioavailable RSV fusion protein inhibitor. This study recounts the results of the 2-part proof-of-concept Phase 2 study testing AK0529 in infants aged 1 to 24 months and hospitalized with RSV.

Participants in this study were all infants aged between 1 and 24 months and weighing less than 3 kg at the screening. All participants were enrolled from May 2016 to April 2019.

In the double-blind, placebo-controlled, randomized, multicenter study, researchers had a primary objective of evaluating the safety and tolerability of single and multiple oral doses of AK0529. The secondary objective was to assess the effect of AK0529 on Wang Respiratory Score and viral load.

All participants were randomized at a 2-to-1 ratio to receive either AK0529 or placebo, respectively. All participants were stratified by age, with infants aged 6 to 24 months in cohorts 1 and 3 and infants aged 1 to 6 months in cohorts 2 and 4. The first part of the study had all participants receive a single dose with a 7-day follow up, with doses in cohort 1 being 4, 2, and 1 mg/kg. The second part involved participants receiving AK0529 or a placebo over 5 days and followed for 14 days afterward.

The Wang Respiratory Score was used to assess severity of respiratory rate on a scale of 0 to 12, with 12 being the most severe. Safety and tolerability were evaluated through a clinical assessment.

There were 73 participants in this study, 20 of whom were from Australia, 39 from Taiwan, 8 from Malaysia, 3 from Israel, and 3 from Turkey. There were 10 participants infected with RSV-A and 13 with RSV-B in Part 1 and 23 participants infected with RSV-A and 25 with RSV-B in part 2.

The median Wang Respiratory Score decreased from baseline to 24 hours in the participants who received AK0529, but not in the placebo group. There was a –4.0 median reduction (95% CI, –4.51 to –2.03) from baseline to 96 hours in the 2 mg/kg AK0529 group in Part 2, compared with –2.0 (95% CI, –3.42 to –1.82) in the placebo group.

A post-hoc analysis found that 73% of patients who received AK0529 2 mg/kg achieved disease remission by the fifth day compared with 31% in the placebo group.

There were 3 participants who experienced a Grade 1 treatment-emergent adverse event (TEAE). There were 2 serious TEAEs reported, 1 of which was grade 4 and another grade 2. However, these were found to be unrelated to the treatment and were both resolved.

There were some limitations to this study. There was limited follow-up time, meaning the potential for a rebound could not be addressed. The pre-defined primary timepoint for the analysis was not the 96-hour timepoint that was used and was not adjusted for the analyses. There are also differences in health care and insurance policy that prevented analysis of therapy and length of hospital stay on treatment of RSV. There was also limited information on patients' need for respiratory support at baseline.

The researchers concluded that the 2 mg/kg dose of AK0529 had an effect on viral load and clinical signs and symptoms of infection and hospitalization for RSV in infants.

Reference

Huang LM, Schibler A, Huang YC, et al. Safety and efficacy of AK0529 in respiratory syncytial virus-infected infant patients: a phase 2 proof-of-concept trial. Influenza Other Respir Viruses. 2023;17:e13176. doi:10.1111/irv.13176