Lucinactant

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Lucinactant
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Trade names Surfaxin
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Lucinactant (trade name Surfaxin) is a liquid medication used to treat infant respiratory distress syndrome. [1] It is a pulmonary surfactant for infants who lack enough natural surfactant in their lungs. Whereas earlier medicines of the class, such as beractant (Survanta & Beraksurf), calfactant (Infasurf), and poractant (Curosurf), are derived from animals, lucinactant is synthetic. It was approved for use in the United States by the U.S. Food and Drug Administration (FDA) on March 6, 2012. [2]

Contents

Medical uses

Lucinactant is indicated to improve lung function and reduce duration and risk of mechanical ventilation in children. It can be used up to two years of age and is specified for children who are diagnosed with acute respiratory failure following exposure to a pathogen such as RSV or influenza, including H1N1. [3] [4] [5] Lucinactant is also used to treat meconium aspiration syndrome. [5] [6]

Chemistry

Lucinactant contains the peptide sinapultide (KL4 acetate, KLLLLKLLLLKLLLLKLLLLK), dipalmitoylphosphatidylcholine, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (as the sodium salt), and palmitic acid.[ citation needed ]

History

The scientific groundwork for lucinactant was laid in the laboratory of Charles Cochrane at The Scripps Research Institute in the 1990s. [7] The drug was then developed by Discovery Laboratories of Warrington, PA. The path through the approval process was unusually long, reflecting in part challenges in the manufacturing process that needed to be addressed before approval was granted. [8]

Lucinactant is listed as an Orphan Drug Product by the US Food and Drug Administration for several conditions: [9] [10]

Clinical trials in Latin America were criticized for protocol based in potentially unethical principles. [11] A placebo was used and considered ethical by design since infants born in Latin America usually do not have access to life saving treatment. The intent of Discovery Labs was always to market Surfaxin in the United States, implying burdens on the Latin American children that outweighed the benefits.[ citation needed ]

Related Research Articles

Meconium aspiration syndrome Medical condition affecting newborn infants

Meconium aspiration syndrome (MAS) also known as neonatal aspiration of meconium is a medical condition affecting newborn infants. It describes the spectrum of disorders and pathophysiology of newborns born in meconium-stained amniotic fluid (MSAF) and have meconium within their lungs. Therefore, MAS has a wide range of severity depending on what conditions and complications develop after parturition. Furthermore, the pathophysiology of MAS is multifactorial and extremely complex which is why it is the leading cause of morbidity and mortality in term infants.

Infant respiratory distress syndrome

Infantile respiratory distress syndrome (IRDS), also called respiratory distress syndrome of newborn, or increasingly surfactant deficiency disorder (SDD), and previously called hyaline membrane disease (HMD), is a syndrome in premature infants caused by developmental insufficiency of pulmonary surfactant production and structural immaturity in the lungs. It can also be a consequence of neonatal infection and can result from a genetic problem with the production of surfactant-associated proteins. IRDS affects about 1% of newborns and is the leading cause of death in preterm infants. Notably, data has shown the choice of elective caesarean sections to strikingly increase the incidence of respiratory distress in term infants; dating back to 1995, the UK first documented 2,000 annual caesarean section births requiring neonatal admission for respiratory distress.The incidence decreases with advancing gestational age, from about 50% in babies born at 26–28 weeks to about 25% at 30–31 weeks. The syndrome is more frequent in males, Caucasians, infants of diabetic mothers and the second-born of premature twins.

Liquid breathing respiration of oxygen-rich liquid by a normally air-breathing organism

Liquid breathing is a form of respiration in which a normally air-breathing organism breathes an oxygen-rich liquid, rather than breathing air.

Transient tachypnea of the newborn is a respiratory problem that can be seen in the newborn shortly after delivery. It is caused by retained fetal lung fluid due to impaired clearance mechanisms. It is the most common cause of respiratory distress in term neonates. It consists of a period of rapid breathing. Usually, this condition resolves over 24–72 hours. Treatment is supportive and may include supplemental oxygen and antibiotics. The chest x-ray shows hyperinflation of the lungs including prominent pulmonary vascular markings, flattening of the diaphragm, and fluid in the horizontal fissure of the right lung.

Neonatology Medical care of newborns, especially the ill or premature

Neonatology is a subspecialty of pediatrics that consists of the medical care of newborn infants, especially the ill or premature newborn. It is a hospital-based specialty, and is usually practised in neonatal intensive care units (NICUs). The principal patients of neonatologists are newborn infants who are ill or require special medical care due to prematurity, low birth weight, intrauterine growth restriction, congenital malformations, sepsis, pulmonary hypoplasia or birth asphyxia.

Pulmonary surfactant

Pulmonary surfactant is a surface-active lipoprotein complex (phospholipoprotein) formed by type II alveolar cells. The proteins and lipids that make up the surfactant have both hydrophilic and hydrophobic regions. By adsorbing to the air-water interface of alveoli, with hydrophilic head groups in the water and the hydrophobic tails facing towards the air, the main lipid component of surfactant, dipalmitoylphosphatidylcholine (DPPC), reduces surface tension.

Antenatal steroids, also known as antenatal corticosteroids, are medications administered to pregnant women expecting a preterm birth. When administered, these steroids accelerate the maturation of the fetus' lungs, which reduces the likelihood of infant respiratory distress syndrome and infant mortality. The effectiveness of this corticosteroid treatment on humans was first demonstrated in 1972 by Sir Graham Liggins and Ross Howie, during a randomized control trial using betamethasone.

Bronchopulmonary dysplasia

Bronchopulmonary dysplasia is a chronic lung disease in which premature infants, usually those who were treated with supplemental oxygen, require long-term oxygen. The alveoli that are present tend to not be mature enough to function normally. It is more common in infants with low birth weight (LBW) and those who receive prolonged mechanical ventilation to treat respiratory distress syndrome (RDS). It results in significant morbidity and mortality. The definition of BPD has continued to evolve primarily due to changes in the population, such as more survivors at earlier gestational ages, and improved neonatal management including surfactant, antenatal glucocorticoid therapy, and less aggressive mechanical ventilation.

Tyloxapol

Tyloxapol is a nonionic liquid polymer of the alkyl aryl polyether alcohol type. It is used as a surfactant to aid liquefaction and removal of mucopurulent bronchopulmonary secretions, administered by inhalation through a nebulizer or with a stream of oxygen.

Perflubron

Perflubron is a contrast medium for magnetic resonance imaging, computer tomography and sonography. It was approved for this use in the United States by the Food and Drug Administration in 1993.

Wilson–Mikity syndrome, is a rare lung condition that affects low birth weight babies.

Persistent fetal circulation is a condition caused by a failure in the systemic circulation and pulmonary circulation to convert from the antenatal circulation pattern to the "normal" pattern. Infants experience a high mean arterial pulmonary artery pressure and a high afterload at the right ventricle. This means that the heart is working against higher pressures, which makes it more difficult for the heart to pump blood.

Lecithin–sphingomyelin ratio

The lecithin–sphingomyelin ratio is a test of fetal amniotic fluid to assess for fetal lung immaturity. Lungs require surfactant, a soap-like substance, to lower the surface pressure of the alveoli in the lungs. This is especially important for premature babies trying to expand their lungs after birth. Surfactant is a mixture of lipids, proteins, and glycoproteins, lecithin and sphingomyelin being two of them. Lecithin makes the surfactant mixture more effective.

Diffuse alveolar damage

Diffuse alveolar damage (DAD) is a histologic term used to describe specific changes that occur to the structure of the lungs during injury or disease. Most often DAD is described in association with the early stages of acute respiratory distress syndrome (ARDS). It is important to note that DAD can be seen in situations other than ARDS and that ARDS can occur without DAD.

Beractant, also known by the trade name of Survanta, is a modified bovine pulmonary surfactant containing bovine lung extract, to which synthetic DPPC, tripalmitin and palmitic acid are added. The composition provides 25 mg/mL phospholipids, 0.5 to 1.75 mg/mL triglycerides, 1.4 to 3.5 mg/mL free fatty acids, and <1.0 mg/mL total surfactant proteins. As an intratracheal suspension, it can be used for the prevention and treatment of neonatal respiratory distress syndrome. Survanta is manufactured by Abbvie.

Pulmonary interstitial emphysema Collection of air outside of the normal air space of the pulmonary alveoli

Pulmonary interstitial emphysema (PIE) is a collection of air outside of the normal air space of the pulmonary alveoli, found instead inside the connective tissue of the peribronchovascular sheaths, interlobular septa, and visceral pleura. This collection of air develops as a result of alveolar and terminal bronchiolar rupture. Pulmonary interstitial emphysema is more frequent in premature infants who require mechanical ventilation for severe lung disease. Infants suffering from pulmonary interstitial emphysema are typically recommended for admission to a neonatal intensive care unit.

Surfactant therapy is the medical administration of exogenous surfactant. Surfactants used in this manner are typically instilled directly into the trachea. When a baby comes out of the womb and the lungs are not developed yet, they require administration of surfactant in order to process oxygen and survive. This condition that the baby has is called newborn respiratory distress syndrome, and it is treatable. Surfactant coat the smallest parts of the lungs called the alveoli and helps for oxygen to go in and for carbon dioxide to go out. How surfactant does this is by not allowing the alveoli to collapse and to retain their inflated shape when the baby exhales.

Discovery Laboratories, Inc is an American company which was set up in 1992 and now is based in Warrington, Pennsylvania, developing drug products for patients with respiratory disease. The company joined an alliance with Laboratorios del Dr. Esteve, S.A. In 2016, Discovery Laboratories changed name to Windtree Therapeutics, Inc.

Henrik Verder

Henrik Verder is a pediatrician and the inventor of the INSURE method combined with nasal CPAP. In 1989 he used this pioneering method to successfully treat the first premature infant with severe RDS. Verder is a significant researcher within the field of paediatrics, with more than 50 publications and over 500 citations.

Pulmonary surfactant (medication)

Pulmonary surfactant is used as a medication to treat and prevent respiratory distress syndrome in newborn babies.

References

  1. ↑ "Surfaxin". Discovery Labs. Archived from the original on April 20, 2009.
  2. ↑ "FDA approves Surfaxin to prevent breathing disorder in premature infants". Fda.gov. 2012-03-06. Retrieved 2012-10-20.
  3. ↑ "POPG, a Key Component of Discovery Labs' KL4 Surfactant, Identified as a Novel Anti-Viral Therapeutic Approach". Archived from the original on January 22, 2010.
  4. ↑ Wiswell TE, Smith RM, Katz LB, Mastroianni L, Wong DY, Willms D, et al. (October 1999). "Bronchopulmonary segmental lavage with Surfaxin (KL(4)-surfactant) for acute respiratory distress syndrome". American Journal of Respiratory and Critical Care Medicine. 160 (4): 1188–95. doi:10.1164/ajrccm.160.4.9808118. PMID   10508806.
  5. 1 2 Donn SM (March 2005). "Lucinactant: a novel synthetic surfactant for the treatment of respiratory distress syndrome". Expert Opinion on Investigational Drugs. 14 (3): 329–34. doi:10.1517/13543784.14.3.329. PMID   15833063. S2CID   6843316.
  6. ↑ Wiswell TE, Knight GR, Finer NN, Donn SM, Desai H, Walsh WF, et al. (June 2002). "A multicenter, randomized, controlled trial comparing Surfaxin (Lucinactant) lavage with standard care for treatment of meconium aspiration syndrome". Pediatrics. 109 (6): 1081–7. doi:10.1542/peds.109.6.1081. PMID   12042546.
  7. ↑ "Scripps Research Discoveries Lead to Newly Approved Drug for Infant Respiratory Distress Syndrome". Scripps.edu. 2012-03-06. Retrieved 2012-10-20.
  8. ↑ "Pharmaceutical News - Discovery Labs Turns Focus To Surfaxin Market Strategy - October 20, 2012". Pharmacy Choice. Retrieved 2012-10-20.
  9. ↑ "List Of Orphan Products Designations And Approvals". Google2.fda.gov. Retrieved 2012-10-20.
  10. ↑ "US FDA grants "orphan drug" status for sinapultide (Surfaxin) for chronic lung disease in premature infants". Nelm.nhs.uk. Archived from the original on 2010-04-14. Retrieved 2012-10-20.
  11. ↑ Charatan F (March 2001). "Surfactant trial in Latin American infants criticised". BMJ. 7286. 322 (7286): 575. doi:10.1136/bmj.322.7286.620. PMC   1119782 . PMID   11238147.
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