Bronchopulmonary Dysplasia (BPD)

Bronchopulmonary Dysplasia (BPD), rhSP-D in combination with a natural surfactant

Bronchopulmonary dysplasia, a chronic lung disorder that affects approximately 5,000 newborns annually in the US, is most common among children who were born prematurely with very low birth weights (almost 50% of those between 500 and 1250g)[1], and who received mechanical ventilation with elevated amounts of oxygen to prevent or treat what is called neonatal respiratory distress syndrome (nRDS)[2]. The target market for BPD would be approximately the same as the total market for nRDS since virtually every neonate resuscitated with a surfactant would also benefit from protection from BPD. At present, infants born prematurely with very low birth weights (VLBW by definition is <1,500g)[3] are generally resuscitated with surfactant. The data for 2007 were recently published and indicate that 1.48% of live births in the US are VLBW[3]. By calculation, there were just under 64,000 VLBW infants born in the US out of 4,317,119 live births. According to the Vermont Oxford Network (VON) database[4], 63.6% of VLBW infants received a surfactant at any time in the patient’s care. That means that just over 40,000 premature neonates would comprise the main target market. The number of VLBW infants (the target group for surfactant treatment) has been increasing gradually over at least the past 20 years[3]. A large number of babies outside that weight range receive surfactants for respiratory conditions, so that 40,000 is believed to be a low estimate of the true target market population in the US. One US surfactant manufacturer lists the number of neonates treated with surfactant annually in the US at approximately 50,000[5].

Currently, only animally derived surfactants (Curosurf, Infasurf and Survanta) are approved in the United States to prevent and treat nRDS, administered by intra-tracheal injection in intubated patients. The current plan is to partner with one of the three companies that market an existing animal surfactant in the US, in order to formulate rhSP-D into a final combination product. It is expected that the new surfactant-rhSP-D combination product will retain the existing labeling for the prevention and treatment of nRDS, and also be labeled for the prevention of BPD, based upon preliminary evidence in an animal model[6]. None of the currently marketed animal surfactants is labeled for the indication of the prevention of BPD. The addition of rhSP-D to an existing animal surfactant should become the new standard of care and capture the majority of the animally derived surfactant market since physicians would not want to run the risk of treating high-risk premature newborns without added protection against BPD.

Airway Therapeutics, Inc. has consulted with US and international neonatologists to estimate the percentage of VLBW infants likely to use or benefit from the company’s product. Based on initial research, the Company assumes that the combination surfactant-SP-D will become the new standard of care for neonates requiring resuscitation with a surfactant. Based on an assumption of acceptance by the company’s small sampling of treating neonatologists, we estimate the market share may be close to 70% within 3-4 years of launch. This target is based on the assumption that a new standard of care will have been established for the resuscitation of premature VLBW neonates with only one product able to prevent the morbidity and mortality associated with BPD.

In the coming years, it is expected that sophisticated synthetic surfactants, as they are approved, will replace animal-derived surfactants in the prevention and treatment of nRDS. Synthetic surfactants should be easier and less expensive to produce than animal surfactants, and will not suffer from concerns about an animal origin (even though to date there have been no problems with the animal surfactants), so the synthetics are expected to replace a significant part of the animal surfactant market. Without an SP-D component, these synthetic surfactants will also not be able to achieve a claim of preventing BPD. Airway Therapeutics is planning to partner with a synthetic surfactant developer during development to add further benefit to the partner’s product, making that synthetic surfactant-rhSP-D combination the only synthetic surfactant product able to prevent BPD.

References

  1. Schmidt, B., et al., Caffeine therapy for apnea of prematurity. N Engl J Med, 2006. 354(20): p. 2112-21.
  2. Northway, W.H., Jr., R.C. Rosan, and D.Y. Porter, Pulmonary disease following respirator therapy of hyaline-membrane disease. Bronchopulmonary dysplasia. N Engl J Med, 1967. 276(7): p. 357-68.
  3. Heron, M., et al., Annual summary of vital statistics: 2007. Pediatrics, 2010. 125(1): p. 4-15.
  4. Soll, R., Vermont Oxford Network. 2010.
  5. Cornerstone Therapeutics, I. CUROSURF® (poractant alfa) Intratracheal Suspension. 2011; Available from: http://www.crtx.com/products/curosurf®.html.
  6. Sato, A., et al., Surfactant protein-d inhibits lung inflammation caused by ventilation in premature newborn lambs. Am J Respir Crit Care Med, 2010. 181(10): p. 1098-105.