CHF5633

Summary

CHF5633 is a fully synthetic pulmonary surfactant that combines phospholipids with peptide analogues of human surfactant proteins SP‑B and SP‑C. It is being investigated for replacement therapy in preterm infants with respiratory distress syndrome (RDS) and has been studied in animal models, early human cohort studies, and a multicenter randomized trial.

Mechanism of Action

The formulation contains dipalmitoylphosphatidylcholine and phosphatidylglycerol to provide a lipid monolayer that lowers alveolar surface tension. The SP‑B and SP‑C peptide analogues mimic the activity of native surfactant proteins, promoting rapid adsorption of the lipid film, enhancing stability during breathing cycles, and improving lung compliance and gas exchange.

What the Research Shows

A 2012 lamb study showed CHF5633 restored lung function and modestly outperformed the animal‑derived surfactant Survanta in tidal volume and compliance. A first‑in‑human cohort (40 infants, 100–200 mg/kg) reported rapid, sustained reductions in FiO2 in 98 % of participants, with adverse events limited to typical prematurity complications and one transient tube obstruction; no systemic absorption or antibodies were detected. A 2020 double‑blind multicenter trial (123 infants, 200 mg/kg) compared CHF5633 to poractant alfa and found no significant differences in oxygen requirement, respiratory severity scores, bronchopulmonary dysplasia, or mortality, and a similar safety profile. Reviews note its potential as a consistently manufactured synthetic alternative, but larger, long‑term studies are pending.

Reported Benefits

Evidence indicates CHF5633 rapidly improves oxygenation in preterm infants with RDS, achieving outcomes comparable to the established porcine surfactant poractant alfa. Its fully synthetic composition may reduce reliance on animal sources, potentially lowering batch‑to‑batch variability and risk of pathogen transmission. Early animal data suggest a slight advantage in lung mechanics over some animal‑derived products.

Limitations of the Evidence

Human data are limited to small cohorts and a single randomized trial, providing only short‑term efficacy and safety information. No superiority over existing surfactants has been demonstrated, and long‑term outcomes such as neurodevelopment or chronic lung disease remain unstudied. Production advantages are theoretical until commercial availability is achieved.

Safety Considerations

CHF5633 was generally well tolerated. Reported adverse events were mostly expected complications of prematurity; a rare adverse drug reaction involved transient endotracheal tube obstruction after a 200 mg/kg dose. No systemic absorption, immunogenicity, or antibody formation was observed in the studies. Caution is advised when administering high doses to monitor for airway blockage.

How It Is Administered

The surfactant is delivered intratracheally as a suspension. Clinical investigations have used single doses of 100 mg/kg or 200 mg/kg, with optional redosing at 100 mg/kg if needed. Formulations are designed for nebulized or instilled administration directly into the airway of intubated neonates.

Routes of Administration

Goals & Uses

• Animal-free surfactant alternativePharmacological / SafetyLow
• Treatment of Neonatal Respiratory Distress Syndrome (RDS)Pulmonary / NeonatalModerate
• Reduction of need for mechanical ventilationPulmonary / NeonatalModerate

Contraindications

• Known hypersensitivity to any componentAllergy / ImmunologicHigh
• Congenital anomalies incompatible with lifeNeonatal / StructuralHigh

Adverse Effects

• Airway obstructionPulmonaryRare
• Oxygen desaturationPulmonaryUncommon
• Pulmonary hemorrhagePulmonaryRare
• BradycardiaCardiovascularUncommon

Drug Interactions

• Inhaled nitric oxideLow

Population Constraints

• Term neonates and pediatric/adult patientsAgeRelative
• Preterm neonates <27 weeks gestational ageNeonatal / Gestational AgeRelative

Regulatory Status

• European UnionInvestigationalInvestigated under EMA oversight; Phase II data published. No marketing authorization granted as of knowledge cutoff.
• United StatesInvestigationalNo FDA approval; IND status assumed for clinical trial conduct.
• United KingdomInvestigationalNo MHRA marketing authorization; clinical research status.

CHF5633 has been evaluated in Phase II clinical trials in preterm infants with RDS. It has not yet received marketing approval from major regulatory agencies (FDA, EMA) as of the knowledge cutoff. Orphan drug designations may apply given the neonatal indication.

Evidence & Sources

• SP-B and SP-C containing new synthetic surfactant for treatment of extremely immature lamb lung
  Journal ArticleLowSato A, Ikegami M2012-01-01T00:00:00.000000Z
• A unique story in neonatal research: the development of a porcine surfactant
  Journal ArticleModerateCurstedt T, Halliday HL, Speer CP2015-01-01T00:00:00.000000Z
• Synthetic surfactant CHF5633 vs poractant alfa
  Journal ArticleUngradedRazak A, Suresh Gautham K2020-01-01T00:00:00.000000Z
• Synthetic Surfactant CHF5633 Compared with Poractant Alfa in the Treatment of Neonatal Respiratory Distress Syndrome: A Multicenter, Double-Blind, Randomized, Controlled Clinical Trial
  Journal ArticleModerateRamanathan R, et al.2020-01-01T00:00:00.000000Z
• Surfactant preparations for preterm infants with respiratory distress syndrome: past, present, and future
  Journal ArticleModerateJeon GW2019-01-01T00:00:00.000000Z
• A first-in-human clinical study of a new SP-B and SP-C enriched synthetic surfactant (CHF5633) in preterm babies with respiratory distress syndrome
  Journal ArticleModerateSweet DG, et al.2017-01-01T00:00:00.000000Z

Frequently Asked Questions