Lung surfactant - lucinactant

The lungs produce lipoprotein pulmonary surfactant which lines the alveolar epithelium, reducing surface tension.

This aids the expansion of the alveoli, allowing gas exchange to take place. Its other functions include providing a physical barrier to inhaled particles and noxious gases, and it is involved in a variety of antiinfection and antiinflammatory responses.

A shortage or lack of lung surfactant is associated with a number of severe respiratory disorders for which there is no specific treatment, including meconium aspiration syndrome (MAS) and acute respiratory distress syndrome (ARDS). Very premature babies are particularly at risk. Some form of surfactant replacement therapy should be an effective treatment, but current products have disadvantages. Largely developed from pig or cow lungs, their make-up is variable, there can be problems with formulation, and there is the risk of immune responses or exposure to animal-borne diseases.

One promising new product, lucinactant, was developed at the Scripps Research Institute in California, and licensed to US company Discovery Laboratories and Laboratorios del Dr Esteve in Spain. It is a humanised engineered version of natural lung peptide, based on the 21 residue peptide sinapultide, or KL4. This is designed to mimic the endogenous human surfactant protein B. Lucinactant also contains DPPC, palmitoyloleoyl phosphatidylglycerol and palmitic acid. The product can be formulated as a wet aerosol, dry powder aerosol or an instillate.

An open label uncontrolled Phase Ib trial was carried out in 12 adults with ARDS.¹ Four days after the patients were given lucinactant by sequential bronchopulmonary segmental lavage in various doses, decreases in the fraction of inspired oxygen and positive end expiratory pressure were seen.

Its safety and efficacy were compared to standard therapy in a randomised open label controlled Phase I/II trial in 22 newborn babies with MAS.² It was safe and well tolerated, and those given lucinactant were able to be removed from mechanical ventilation a third more quickly than those given standard therapy.

A multicentre randomised Phase III trial has also been carried out, in nearly 1,300 premature babies. It was compared to synthetic surfactant Exosurf, which contains no protein, and Survanta, which is derived from cows. Lucinactant gave statistically significantly better survival rates.

In a further Phase III trial, 243 very premature babies were treated either with lucinactant or the animal-derived surfactant portactant.³ At the end of the trial, 38% of those given lucinactant were alive and showed no signs of bronchopulmonary dysplasia, compared with 33.1% of those in the control group. Trials continue, and an NDA has been filed with the US FDA for the prevention of RDS in premature babies.