AeroFact

Non-Invasive Surfactant  Administration 
a long-awaited advance in treatment of respiratory distress syndrome in preterm infants

AeroFactTM Overview 

for treatment of respiratory distress syndrome (RDS) in premature infants

AeroFactTM is an investigational, biologic/device combination product, poised to deliver a major advance in the treatment of respiratory distress syndrome (RDS) in premature infants.  AeroFactTM enables trans-nasal pulmonary delivery of surfactant replacement therapy (SRT) to infants on nasal continuous positive airway pressure (nCPAP) or non-invasive ventilation (NIV).


AeroFact is based on the combination of a clinically-proven bovine lung surfactant (SF-RI 1, also known as Alveofact® or Bovactant®) with a precise and highly efficient nasal delivery system. Alveofact® is approved as an RDS treatment in 27 countries, with class-leading, three-year room temperature stability and a 30-year record of safety and efficacy when administered by conventional instillation techniques.


AeroFact™ Clinical Perspective

RDS is a complication of prematurity, caused primarily by the lack of pulmonary surfactant production by the immature lung. The risk of RDS increases as gestational age decreases. It occurs in approximately 1.4 million infants worldwide each year. In the US alone, an estimated 40,000 infants are born each year with RDS.

Surfactant replacement therapy (SRT) has been a cornerstone of neonatal intensive care since the 1980s and has had a remarkable effect on the incidence of morbidity and mortality associated with preterm birth. SRT relies on instilling a bolus of liquid surfactant into the trachea of the infant, and can be accomplished by various techniques with varying degrees of invasiveness (e.g. with intubation for ventilation, via INSURE, or via LISA/MIST).

However, all these techniques require laryngoscopy to visualize the vocal cords and placement of a tube through the vocal cords. These techniques can be technically challenging, are frequently associated with bradycardia and significant decrease in oxygenation, and cause discomfort for the infant (unless performed with anesthesia).

Due to the challenges associated with laryngoscopy and instillation of surfactant, multiple attempts have been made to treat RDS by delivering aerosolized surfactant to infants. However, despite more than 50 years of research, there are no approved or clinically effective approaches to delivery of aerosolized surfactant.

Until now, major technical challenges have limited the delivery of an adequate dose of aerosolized surfactant to the alveoli:

  • Aerosol particle size is critical for alveolar delivery
  • Aerosol generation must be as close as possible to the infant’s upper airway to minimize aerosol loss by deposition in the respiratory circuit or in bias gas flow
  • Continuous aerosol generation is wasteful since none of the aerosolized drug reaches the alveoli during the end-inspiration or exhalation phases of the respiratory cycle

AeroFact™ is an investigational biologic /device combination product. The drug component is SF-RI 1, a bovine-derived surfactant also known as Bovactant or Alveofact®, which has been used as prophylaxis treatment to prevent RDS in infants for more than 30 years. The device component includes a vibrating mesh nebulizer which aerosolizes surfactant at the nasal interface and a controller which synchronizes aerosol generation with the infant’s inspiration.

AeroFact™ uses a combination of novel approaches to overcome the barriers of aerosolizing surfactant for the infant with RDS who is supported with NCPAP or non-invasive ventilation:

  • Surfactant is aerosolized with a unique vibrating mesh nebulizer which produces a uniform aerosol with < 3 μm MMAD, the optimal particle size for alveolar deposition
  • Aerosolization occurs at the nasal interface, minimizing surfactant loss due to flow through the circuit
  • Aerosolization is synchronized to the infant’s early- and mid-inspiratory phase, so no aerosol is wasted during end-inspiration or exhalation

Phase 2a study

An open-label trial comparing AeroFact™ treated infants to historical controls in Australia has shown the potential for effective treatment of RDS symptoms. Although not powered to reach statistical significance (30 patients treated with AeroFact), this study showed a trend towards a reduction in the need for instilled bolus liquid surfactant compared to matched historical controls. Importantly, AeroFact™ appeared to be safe and well tolerated. Read more.

Phase 2b studies

A 261-patient randomized controlled study in US and Canada designed to assess the clinical efficacy, safety, and tolerability of AeroFact™ at two dose levels, with the primary aim of determining an optimal dose of AeroFact™ to reduce the need for conventional invasive surfactant instillation. This trial has completed enrollment and results are expected by late 2023.

A 332-patient randomized controlled study in South Africa to investigate whether AeroFact™ treatment can decrease the need for bolus surfactant in infants with RDS. This study is sponsored by The Bill & Melinda Gates Foundation and began in April 2023 with the aim of enrolling 332 infants.

Phase 3 study

A registration study to determine whether infants treated with AeroFact™ and nCPAP/NIV are less likely to meet the pre-determined criteria for bolus surfactant instillation than Control infants treated with nCPAP/NIV alone. This study is planned to begin in early 2024.

AeroFact™ Technical Features

Since pulmonary surfactant deficiency was first identified as the cause of RDS more than 60 years ago, major technical challenges have frustrated the development of a non-invasive surfactant delivery method:

  • Aerosol droplets must be small enough to pass through the upper airways to deposit on the alveolar surface
  • Aerosol must be generated as close as possible to the infant’s airway to minimize losses by deposition in the respiratory circuit or in bias flow gas
  • Aerosol generation throughout the respiratory cycle is wasteful, since none of the drug aerosolized between inspirations is inhaled

Breakthrough technology achieves high-efficiency, cost-effective inhaled delivery for optimal lung dose efficacy

  • Next-generation PDAP mesh technology turns undiluted surfactant into an ultra-fine, ultra-respirable aerosol plume with 1-3 μm droplets.
  • Integration of PDAP nebulizer with a custom nasal interface design minimizes aerosol losses in the delivery circuit
  • Synchronization of aerosol delivery with inspiration maximizes drug deposition and minimizes waste

Learn more

AeroFact™ Potential Clinical Advantages

  • Estimated alveolar dose delivery ≥ 40% of nominal dose
  • Totally non-invasive – no need for laryngoscopy and intubation/cannulation
  • No interruption of oxygen or nCPAP/PEEP pressure during aerosol delivery
  • Spontaneous breathing throughout aerosol delivery
  • Well tolerated by babies in Phase 2a study – no need for sedation/anesthesia






Development Status

AeroFact™ has received Fast Track, Rare Pediatric Disease and Orphan Drug designations from the FDA and EMA

Indication Statement

Caution: AeroFact™ is an investigational biologic/device combination product, limited by Federal law to investigational use.

AeroFact™ is indicated for the treatment of Respiratory Distress Syndrome (RDS) in spontaneously breathing preterm infants and to reduce the need for invasive endotracheal intubation/cannulation, surfactant instillation, and mechanical ventilation.

Statutory Notice on Expanded Access Program under 21 CFR 312

Drug development programs in receipt of FDA Fast Track status are obligated to establish a policy concerning an Expanded Access Program. At this time, Aerogen Pharma is not offering access to AP-001 outside of registered clinical trials.

Trial registration

We are also exploring the possibilities of other clinical applications for inhaled surfactant.

A Phase 2 study of aerosol surfactant as a treatment of adults with moderate to severe COVID-19 infection was conducted in the UK with funding from the Bill & Melinda Gates Foundation.

Learn more

Aerosolized Surfactant for Low- and Middle-Income Countries 

Every year around the world, an estimated 1.4 million neonates develop respiratory distress syndrome (RDS), with two-thirds occurring in low- and middle-income countries (LMICs) where access to intensive care facilities is limited¹,². RDS is the leading cause of death among preterm infants in LMICs, with fatality rates reported to range from 57% to 89% ³. Although pulmonary surfactant was added to the WHO Essential Drug List in 2008, access to this gold standard treatment for RDS is limited in LMICs due to high drug costs, lack of personnel trained to administer surfactant, and shortage of the sophisticated medical equipment necessary to enable invasive mechanical ventilation and endotracheal instillation. One bright spot is that non-invasive CPAP ventilation is becoming more available in many LMICs as the primary mode of managing RDS ⁴. It is our belief that a surfactant delivered through CPAP ventilation has an important role to play in expanding the benefits of surfactant replacement therapy to a wider population.

Aerogen Pharma has received funding from the Bill & Melinda Gates Foundation to develop Efficient, Safe, Feasible and Cost-Effective surfactant treatment for preterm infants in LMICs. Our shared goal is to see fewer families touched by the tragedy of infant mortality, and more preterm babies survive to enjoy full and productive lives.

AeroFact™ Proof-of-Concept Clinical Study in South Africa

The Bill & Melinda Gates Foundation is funding Aerogen Pharma in the conduct of a 332-patient clinical trial of our AeroFact™ inhaled surfactant in South Africa. This study began in April 2023 at four major Neonatal Intensive Care Units in Cape Town & Johannesburg. The enrollment of the first patients took place in May 2023. Our goal for this study is to demonstrate the safety and efficacy of aerosolized surfactant in the South African clinical and public health environment, since it is unwise to assume that clinical advances can be shifted from a high income setting to a LMIC setting without thoughtful adaptation. For more information on this trial, please see the study entry into the registry of the South African Health Products Regulatory Agency.

[1] Sankar MJ J Perinatol 2016 SRT in low-income countries, Journal of Perinatology (2016) 36, S35–S47

[2] Born Too Soon: The Global Action Report on Preterm Birth

[3] Alok Kumar and B. Vishnu Bhat, Alok, Indian J Pediatr 1996; 63: 93-98

[4] Dharmapuri V, Sithembiso V et al, Neonatology 2011;99:355–366


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