Cornerstone Therapeutics, a specialty pharmaceutical company focused on acquiring, developing and commercializing proprietary products for the hospital and respiratory markets, announced a new analysis published in the eFirst Pages section of the Pediatrics website reporting significant benefits in mortality rate and the need for redosing when treating neonatal respiratory distress syndrome (RDS) with Cornerstone's CUROSURF® (poractant alfa) Intratracheal Suspension1.
The objective of the independently performed meta-analysis was to compare the efficacy of CUROSURF versus Survanta® (beractant) and Infasurf® (calfactant) with respect to clinical outcomes among preterm infants with RDS. The analysis was led by Neetu Singh, M.D., at Dartmouth Hitchcock Medical Center.
About the Study
Researchers included the data following a systematic literature search using the methods of the Cochrane Collaboration for Systematic Review of Interventions. As a result, five published randomized controlled trials (RCTs) comparing CUROSURF and Survanta were included in the analysis; enrolling a total of 529 infants. There were no trials that met the designated criteria comparing Infasurf to CUROSURF.
In this review, it is important to note the initial surfactant dose administered to infants in each included RCT. The FDA approved initial dose for CUROSURF is 200 mg/kg versus 100 mg/kg for Survanta. Two of the five RCTs included a subgroup of infants that received a low initial dose of CUROSURF (100 mg/kg). This dose is not approved in the United States therefore the results of that subgroup are not reported in this release.
Following the analysis, authors concluded that the 200 mg/kg initial dose of CUROSURF may result in superior short-term clinical outcomes, compared with Survanta, when used for the treatment of preterm infants with established RDS. There were no significant differences in respect to complications of prematurity between CUROSURF and Survanta.
Key findings of the subgroup comparing the 200 mg/kg initial dose of CUROSURF to the 100 mg/kg of Survanta included:
• A significant reduction in mortality rates was found in infants treated with the 200 mg/kg initial dose of CUROSURF compared with those treated with the 100 mg/kg initial dose of Survanta. Those treated with CUROSURF experienced a relative risk reduction of 70% (RR: 0.29 [95 percent CI: 0.12-0.66], p=.004)
• The need for redosing was significantly lower with the 200 mg/kg initial dose of CUROSURF, with a relative risk reduction of 36 percent compared with the 100 mg/kg initial dose of Survanta (RR: 0.64 [95 percent CI: 0.53-0.83]; p=0.0008)
As with any meta-analysis, there are a few important limitations to note. This systematic review yielded a small number of relevant articles on surfactants that were considered sufficiently rigorous to be included (7 of the 92). In addition, each study included a relatively small patient population.
Due to this, the largest study (Ramanathan R, et al 2004) contributed approximately 55% of all patients included in the analysis, as well as most of the weight and average of the summary treatment effect. Lastly, the included studies analyzed clinical outcomes only until hospital discharge and did not examine long-term outcomes such as neurodevelopmental outcomes.
The authors also noted that the results of this systematic review and meta-analysis are consistent with previously published reviews on this subject. Most recently, a retrospective study compared all-cause, in-hospital mortality in more than 14,000 preterm infants with RDS2. This retrospective study found that the group receiving a 200 mg/kg initial dose of CUROSURF was associated with a significantly reduced likelihood of death compared to Infasurf and a trend toward reduced mortality when compared with Survanta.
"Cornerstone is delighted to see the growing body of data supporting the role of CUROSURF in treating preterm infants struggling with RDS," said Craig A. Collard, Cornerstone's Chief Executive Officer. "Our goal is that this analysis, along with previous published studies, will provide neonatologists the data they need to make an appropriate treatment decision at that critical point in the young patient's life."