Discovery Laboratories, Inc. announced that the Journal of Neonatal-Perinatal Medicine, a prominent, peer-reviewed journal widely distributed to neonatal and paediatric intensive care physicians, recently published a manuscript reviewing an important data analysis from the Surfaxin (lucinactant) phase III clinical trial programme.
The manuscript is entitled “Reintubation and risk of morbidity and mortality in preterm infants after surfactant replacement therapy” (Guardia et al.) in the Journal of Neonatal-Perinatal Medicine (Volume 4, Number 2, 2011). This is the first peer-reviewed manuscript describing neonatal patient compromise following reintubation.
The analysis demonstrates that, for preterm infants at risk for Respiratory Distress Syndrome (RDS) who received prophylactic surfactant therapy and were extubated, subsequent reintubation is a highly predictive risk factor for mortality and major complications of prematurity. The analysis also indicates that infants treated with Surfaxin had a significantly lower incidence of subsequent reintubation and improved survival without reintubation, compared with infants who received comparator animal-derived surfactants Survanta (beractant) and Curosurf (poractant alfa), the current standard of care.
Premature infants are often born with a lack of natural lung surfactant resulting in a diagnosis of RDS. The current treatment for moderate to severe RDS typically requires that the infant be intubated (insertion of a breathing tube into the infant’s airway) to allow for respiratory support via mechanical ventilation and subsequent surfactant administration.
If surfactant therapy appears to be successful, the endotracheal tube is removed from the infant’s airway (extubated) to allow the infant to breathe without mechanical support. However, infants who are extubated following surfactant therapy often relapse and require reintubation. Although increased mortality and morbidity in adults requiring reintubation is well described in medical literature, the consequences of reintubation in preterm infants have not been previously reported.
Data from Discovery Labs’ phase III RDS clinical trials were assessed in a post-hoc analysis to evaluate the consequences of reintubation as well as the potential effect of surfactant choice on reintubation rates and subsequent clinical outcomes in preterm infants. The recently published manuscript highlights the following observations: infants who were successfully extubated and did not require reintubation experienced low mortality rates across all treatment groups, while infants who were subsequently reintubated had a statistically significant higher mortality rate, 0.5% vs. 18%, respectively (p < 0.05).
Infants who required reintubation had significantly higher rates of six major complications of prematurity, including bronchopulmonary dysplasia (BPD, a chronic lung condition), necrotizing enterocolitis (a severe intestinal condition often requiring surgery and loss of bowel), sepsis, and intraventricular haemorrhage (bleeding into the brain). Infants treated with Surfaxin demonstrated a significantly lower reintubation rate compared with those infants treated with animal-derived surfactants, Curosurf (33% vs. 47% respectively; p < 0.05) and Survanta (35% vs. 43% respectively; p < 0.05). Infants treated with Surfaxin demonstrated a significantly higher combined outcome of survival without reintubation compared with those infants treated with animal-derived surfactants, Curosurf (67% vs. 53% respectively; p < 0.05) and Survanta (65% vs. 57% respectively; p < 0.05).
Dr Russell Clayton, vice president of Research and Development of Discovery Labs, commented, “This article is the first published full description of the consequences of reintubation in a preterm neonate population, clearly indicating that, when possible, neonatal medicine practitioners should choose therapeutic options that will optimize the chances of successful extubation. This analysis of our phase III clinical trial data suggests that treatment with Surfaxin may result in lower reintubation rates compared with treatment with currently available surfactant products. We intend to expand upon this current analysis, with specific focus on understanding the potentially favorable impact on NICU health economics by reducing reintubation frequency in neonates.”
Surfaxin is an investigational drug product that has not been approved by the US Food and Drug Administration (FDA) or any other world health regulatory authority. Top-line data of this post-hoc analysis was previously presented at the 2008 American Association for Respiratory Care (AARC) International Respiratory Congress. The full study results reported above include information that may be of interest to healthcare practitioners; however, the clinical relevance of this post-hoc analysis has not been fully established and further scientific investigation may be warranted.
Surfaxin (lucinactant) is Discovery Labs’ lead product based on its proprietary KL4 surfactant technology and represents the first synthetic, peptide–containing surfactant that, if approved, will provide healthcare practitioners with an alternative therapy to the currently-approved, animal-derived surfactants that are standard of care today. The safety and efficacy of Surfaxin for the prevention of RDS has previously been demonstrated in a comprehensive phase III clinical programme.
Discovery Labs filed a New Drug Application (NDA) for Surfaxin for the prevention of RDS in premature infants and received a Complete Response Letter from the FDA in April 2009. Discovery Labs has been conducting a comprehensive preclinical program intended to satisfy the FDA’s requirements with respect to the final validation of an important quality control release and stability test for Surfaxin, the fetal rabbit Biological Activity Test (BAT), and, if successful, anticipates filing a Complete Response to the 2009 Complete Response Letter in the third quarter of 2011. After an anticipated six-month FDA review cycle, which is expected to also include, among other things, pre-approval inspections of Discovery Labs’ manufacturing facility, quality assurance / quality control facilities, third-party raw material suppliers and testing laboratories, Discovery Labs anticipates the potential marketing approval of Surfaxin for the prevention of RDS in premature infants in the United States as early as the first quarter of 2012.
The Journal of Neonatal-Perinatal Medicine's (JNPM) mission is to strengthen research and education of the neonatal and perinatal community on the optimal physical, mental and social health and well-being of infants and pregnant mothers through highest quality publications on neonatal-perinatal medicine and to provide examples of best practices in order to improve the quality, safety and effectiveness of mothers-infants' healthcare worldwide and the vision is to be 'The Reference Journal' in the field of neonatology.