Post-hoc Analysis of AERO-02 Trial Completed

Jul 26, 2023

Analysis results are in: nebulized calfactant reduced the need for instilled liquid surfactant by 50% in infants with clinical RDS born at 28-36 weeks’ gestation.

Today, ONY Biotech reports the new publication of an independent post-hoc analysis of the AERO-02 randomized, controlled clinical trial. The analysis was published in the Journal of Perinatology and can be found here.  Supporting the results from the AERO-02 study, this analysis further demonstrated the use of nebulized calfactant to prevent the need for intubation and liquid surfactant, and the efficacy of ONY Biotech’s drug/device combination product.

This secondary analysis of the AERO-02 trial, by Dr. Kaluarachchi and colleagues, compared the respiratory course of the subgroup of infants born at 28-36 weeks’ gestation with clinical RDS, excluding infants born more preterm.  Current evidence suggests infants born <28 weeks gestation are less likely to benefit from an aerosolized surfactant.

The authors found that nebulized calfactant reduced the need for instilled liquid surfactant by 50%.  Of the infants requiring instilled liquid surfactant, the use of nebulized calfactant delayed that need by several hours, suggesting that it also slowed the progression to more severe RDS.

Beyond the first few hours, the authors found that infants in the usual care group weaned faster from supplemental oxygen and positive pressure non-invasive support presumably because many of them had received instilled liquid surfactant. However, short-term respiratory outcomes were similar between groups.

“While this confirms that instilled liquid surfactant is more effective at reducing respiratory support than aerosolized surfactant, a 50% reduction in instilled liquid surfactant is clinically very important. This means more infants with RDS can avoid intubation and positive pressure ventilation.”

– Dr. James Cummings, Chief Medical Officer of ONY Biotech.

ONY Biotech’s drug/device combination turns their liquid surfactant, Infasurf (calfactant), into a fine mist, which allows a baby to breathe the surfactant in instead of having to be intubated—an invasive process associated with various complications in premature infants. Administered via a modified pacifier, this new method is non-invasive, and study results show it has the potential to reduce the need for intubation by 50 percent in babies.

Nebulized calfactant is an investigational new drug that has not been approved by FDA.

About the AERO-02 Study

Calfactant was aerosolized by using a Solarys nebulizer modified with a pacifier adapter; 6 mL/kg (210 mg phospholipid/kg body weight) were delivered directly into the mouth. Infants in the aerosol group received up to 3 treatments, at least 4 hours apart. Infants in the control group received usual care, determined by providers. Infants were intubated and given instilled surfactant for persistent or worsening respiratory distress, at their providers’ discretion. Among 22 NICUs, 457 infants were enrolled; gestation 23 to 41 (median 33) weeks and birth weight 595 to 4802 (median 1960) grams. In total, 230 infants were randomly assigned to aerosol; 225 received 334 treatments, starting at a median of 5 hours.

The incidence of pulmonary air leaks was similar between groups. Of 334 aerosol treatments, 22 were briefly interrupted, primarily because of surfactant foaming around the pacifier. There were no monitor events (desaturation or bradycardia) during treatment that required intervention.  One treatment was discontinued due to the appearance of what likely was a trace amount of residual blood (either maternal or neonatal) in the infant’s mouth after birth.  One or more severe complications of prematurity occurred in 17 infants (7%) in the aerosol group and 14 infants (6%) in the usual care group. Chronic lung disease, defined as any respiratory support at 28 days of age, was diagnosed in 46 (20%) infants in the aerosol group and 38 infants (17%) in the usual care group (P = .38). There was 1 death in the usual care group due to nonrespiratory causes.