InfaSurf (calfactant) / Samaritan Pharma, Ony Biotech, AbbVie - LARVOL DELTA

Lung surfactant reduces Staphylococcus aureus cytotoxicity and protects host immune cells from membrane damage. (PubMed, Microbiol Spectr) - "Data indicate that cytolytic reduction by mouse and rat surfactants was partially due to surfactants reducing transcript abundance of virulence factors. This work identifies a novel role for surfactants and suggests their importance in modulating the severity of S. aureus lung infections."

Journal • Infectious Disease • Respiratory Diseases • GLS2

SASSIE: Steroids and Surfactant in Extremely Low Gestation Age Infants Dose Escalation Trial (clinicaltrials.gov) - P1/2 | N=25 | Terminated | Sponsor: Cynthia McEvoy | Completed ➔ Terminated

Trial termination • Bronchopulmonary Dysplasia • Pulmonary Disease • Respiratory Diseases

Aero-05: InfasurfAero™ Versus Sham Treatment in Preterm Newborns with RDS (clinicaltrials.gov) - P3 | N=220 | Recruiting | Sponsor: ONY | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Respiratory Distress Syndrome • Respiratory Diseases

Aero-05: InfasurfAero™ Versus Sham Treatment in Preterm Newborns With RDS (clinicaltrials.gov) - P3 | N=220 | Not yet recruiting | Sponsor: ONY | Trial completion date: Dec 2025 ➔ Apr 2026 | Trial primary completion date: Jan 2025 ➔ Jan 2026

Trial completion date • Trial primary completion date • Acute Respiratory Distress Syndrome • Respiratory Diseases

Comparative Biophysical Study of Clinical Surfactants using Constrained Drop Surfactometry. (PubMed, Am J Physiol Lung Cell Mol Physiol) - "At 10 mg/mL, Infasurf, Curosurf, and Survanta all demonstrated excellent dynamic surface activity, while Alveofact exhibited the poorest quasi-static and dynamic surface activity...Understanding the diverse biophysical behaviors of clinical surfactants provides crucial insights for precision and personalized design in treating RDS and other respiratory conditions. The findings from this study contribute valuable perspectives for development of more efficacious and fully synthetic surfactant preparations."

Journal • Acute Respiratory Distress Syndrome • Respiratory Diseases

Comparison of Efficacy and Pharmacoeconomic Outcomes Between Calfactant and Poractant Alfa in Preterm Infants With Respiratory Distress Syndrome. (PubMed, J Pediatr Pharmacol Ther) - "Despite the pharmacoeconomic disadvantage, preterm infants who received poractant alfa needed fewer doses and were less likely to have administration complications compared with those who received calfactant."

HEOR • Journal • Acute Respiratory Distress Syndrome • Bronchopulmonary Dysplasia • Critical care • Pulmonary Disease • Respiratory Diseases

Impact of Nebulization on the Physicochemical Properties of Polymer-Lipid Hybrid Nanoparticles for Pulmonary Drug Delivery. (PubMed, Int J Mol Sci) - "The cellular uptake studies demonstrated that both nebulized and non-nebulized NPs were less readily taken up by alveolar macrophages compared to lung cancer cells, confirming the IFS coating retention. Overall, nebulization did not significantly compromise the physicochemical properties as well as therapeutic efficacy of the prepared nanotherapeutics."

Journal • Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor

Aero-05: InfasurfAero™ Versus Sham Treatment in Preterm Newborns With RDS (clinicaltrials.gov) - P3 | N=220 | Not yet recruiting | Sponsor: ONY | Trial completion date: Sep 2025 ➔ Dec 2025 | Initiation date: Apr 2024 ➔ Jul 2024

Trial completion date • Trial initiation date • Acute Respiratory Distress Syndrome • Respiratory Diseases

Aero-05: InfasurfAero™ Versus Sham Treatment in Preterm Newborns With RDS (clinicaltrials.gov) - P3 | N=220 | Not yet recruiting | Sponsor: ONY | Initiation date: Oct 2023 ➔ Apr 2024

Trial initiation date • Acute Respiratory Distress Syndrome • Respiratory Diseases

SURFACTANT COMPONENT SUPPRESSES STAPHYLOCOCCUS AUREUS TOXIN EXPRESSION (WRMC 2024) - "The treatment of S. aureus with palmitate demonstrates a decrease in hla toxin expression. Because palmitate is a component of healthy surfactant, this data could explain why S. aureus is not a primary agent of community-acquired pneumonia. Instead, the pathogen strikes the post-IAV lung environment when surfactant has been disrupted."

Surfactant • Infectious Disease • Influenza • Pneumonia • Respiratory Diseases • GLS2

Administration of Surfactant Through an Instillation Device Infasurf® (Calfactant) in Neonates- A Pilot Study (clinicaltrials.gov) - P2 | N=55 | Suspended | Sponsor: ONY | Trial completion date: Dec 2021 ➔ Mar 2026 | Active, not recruiting ➔ Suspended | Trial primary completion date: Oct 2020 ➔ Dec 2025

Trial completion date • Trial primary completion date • Trial suspension • Pulmonary Disease • Respiratory Diseases

Aero-05: InfasurfAero™ Versus Sham Treatment in Preterm Newborns With RDS (clinicaltrials.gov) - P3 | N=220 | Not yet recruiting | Sponsor: ONY

New P3 trial • Acute Respiratory Distress Syndrome • Respiratory Diseases

Biophysical Function of Pulmonary Surfactant in Liquid Ventilation. (PubMed, Biophys J) - "It was found that the adsorbed Infasurf film is capable of regulating the interfacial tension of the PFC-water interface within a narrow range between ∼12 mN/m and ∼1 mN/m, during dynamic compression-expansion cycles that mimic liquid ventilation. These findings have novel implications in understanding the physiological and biophysical functions of the pulmonary surfactant film at the PFC-water interface, and may offer new translational insights into the development of liquid ventilation and liquid breathing techniques."

Journal

A new tractable method for generating human alveolar macrophage-like cells in vitro to study lung inflammatory processes and diseases. (PubMed, mBio) - "We developed cell culture conditions that mimic the lung alveolar environment in humans using lung lipids, that is, Infasurf (calfactant, natural bovine surfactant) and lung-associated cytokines (granulocyte macrophage colony-stimulating factor, transforming growth factor-β, and interleukin 10) that facilitate the conversion of blood-obtained monocytes to an AM-like (AML) phenotype and function in tissue culture. We have applied this model to early studies of M. tuberculosis and SARS-CoV-2. This model will significantly advance respiratory biology research."

Journal • Preclinical • Acute Myelogenous Leukemia • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • IL10

Development and characterization of lung surfactant-coated polymer nanoparticles for pulmonary drug delivery. (PubMed, Biomater Adv) - "The anti-cancer drug gemcitabine hydrochloride encapsulated in the PLGA core was released in a sustained manner while the paclitaxel loaded in the LS shell demonstrated a rapid or burst release profile over 21 days...In vivo studies confirmed greater retention of LS-coated NPs in the lungs of C57BL/6 WT mice compared to uncoated NPs, at 24 h and 72 h following intranasal administration. The overall results confirm that LS coating is a unique strategy for cloaking polymeric NPs to potentially prevent their rapid lung clearance and facilitate prolonged pulmonary drug delivery."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Battle of the Surfs: Comparing Calfactant and Poractant Alfa’s Outcomes in Premature Neonates (PAS 2023) - "152 neonates (247 doses of surfactants) were reviewed. 78 infants received Calfactant and 74 infants received Poractant Alfa. There was no statistical difference in the demographics of the two groups, except for birth weight and antenatal steroids (Table 1)."

Acute Respiratory Distress Syndrome • Pulmonary Disease • Respiratory Diseases

A Single-Center Experience with Aerosolized Calfactant in the Treatment of Respiratory Distress Syndrome (PAS 2023) - P3 | "Between 2017 and 2022, we administered aerosolized calfactant to 177 neonates. Twenty-four neonates (13.6%) required rescue intubation, surfactant via endotracheal tube, and mechanical ventilation. In infants < 29 weeks gestation, 2/4 (50%); between 29 to 33 6/7 weeks gestation, 37/45 (82.2 %); and infants ≥ 34 weeks, 114/128 (89.1%) never required rescue intubation."

Clinical • Acute Respiratory Distress Syndrome • Respiratory Diseases

Phase Transitions of the Pulmonary Surfactant Film at the Perfluorocarbon-Water Interface. (PubMed, Biophys J) - "Here we reported the first detailed biophysical study of phospholipid phase transitions in two animal-derived natural pulmonary surfactant films, Infasurf and Survanta, at the PFC-water interface using constrained drop surfactometry (CDS)...The pulmonary surfactant film at the PFC-water interface undergoes continuous phase transitions at surface pressures less than the equilibrium spreading pressure of 50 mN/m, and a monolayer-to-multilayer transition above this critical pressure. These results provided not only novel biophysical insight into the phase behavior of natural pulmonary surfactant at the oil-water interface but also translational implications into the further development of liquid ventilation and liquid breathing techniques."

Journal

Health Economic Studies of Surfactant Replacement Therapy in Neonates with Respiratory Distress Syndrome: A Systematic Literature Review. (PubMed, Pharmacoecon Open) - "There were no significant differences in NICU length of stay or NICU total costs between surfactants evaluated for treating neonates with RDS. However, early use of surfactant was found to be more clinically effective and cost-effective than late treatment. Treatment with poractant alfa was found to be cost-effective versus beractant and cost-saving compared with CPAP alone or beractant or CPAP in combination with calsurf. Limitations included the small number of studies, the geographic scope of the studies and the retrospective study design of the cost-effectiveness studies."

HEOR • Review • Acute Respiratory Distress Syndrome • Critical care • Respiratory Diseases

Comment on "Bilayer aggregate microstructure determines viscoelasticity of lung surfactant suspensions" by C. O. Ciutara and J. A. Zasadzinski, Soft Matter, 2021, 17, 5170-5182. (PubMed, Soft Matter) - "Ciutara and J. A. Zasadzinski, Soft Matter, 2021, 17, 5170-5182.) measured the rheological properties of Infasurf®, Survanta® and Curosurf®, three of the most used pulmonary surfactant substitutes...In contrast, we found that Curosurf® suspensions are viscous Newtonian or slightly shear-thinning fluids, with no evidence of yield stress. The purpose of this Comment is to discuss possible causes for the discrepancy between the two studies, and to suggest that for biological fluids such as surfactant substitutes, the microrheology technique of rotational magnetic spectroscopy (MRS) can provide valuable results."

Journal

TOLSURF: Trial of Late Surfactant for Prevention of Bronchopulmonary Dysplasia (clinicaltrials.gov) - P3; N=511; Completed; Sponsor: Roberta Ballard; Active, not recruiting ➔ Completed

Trial completion • Bronchopulmonary Dysplasia • Pulmonary Disease • Respiratory Diseases

TOLSURF Pilot: Trial of Late Surfactant to Prevent BPD: A Pilot Study in Ventilated Preterm Neonates Receiving Inhaled Nitric Oxide (clinicaltrials.gov) - P3; N=85; Completed; Sponsor: Roberta Ballard; Active, not recruiting ➔ Completed

Clinical • Trial completion • Acute Respiratory Distress Syndrome • Bronchopulmonary Dysplasia • Pulmonary Disease • Respiratory Diseases

Bilayer aggregate microstructure determines viscoelasticity of lung surfactant suspensions. (PubMed, Soft Matter) - "Here we examine the rheology of three clinical lung surfactant suspensions: Survanta (bovine lung), Curosurf (porcine lung), and Infasurf (calf lung)...While the mass loading of the three clinical surfactants is different, the different bilayer organization causes the particle volume fractions to be similar. Adding polyethylene glycol dehydrates and partially flocculates the bilayer aggregates in all suspensions, leading to smaller particle volume fractions and a reduced suspension viscosity even though the solvent viscosity increases almost six-fold."

Journal • Acute Respiratory Distress Syndrome • Respiratory Diseases