Clinical Profile of CUROSURF

Discover how CUROSURF provides fast RDS success. In addition to efficient administration, efficacy during the acute treatment phase is a critically important feature of a surfactant. Rapidly improved oxygenation, sustained efficacy, and fewer doses can all help wean infants to less invasive forms of ventilation.

See the data:

Onset

Dosing

Volume

Distribution

Onset

CUROSURF improves oxygenation within 5 minutes and rapidly reduces FiO₂ requirements over the initial treatment period—delivering better short-term efficacy.^1,2

Physiological end points (eg, faster reduction in FiO₂) have not been proven to impact key clinical outcomes such as mortality due to RDS.

Faster reduction in FiO₂ requirements vs Survanta^® (beractant)³*

Faster reduction graph - see image description

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Line graph (adapted from Ramanathan R, et al. Am J Perinatol. 2004;21:109-119) showing FiO₂ vs time after dosing for 2 treatment groups (poractant alfa 200 mg/kg initial dose and beractant 100 mg/kg initial dose). The mean and standard error are plotted. P<0.05 at all post-treatment time points of 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, and 6 hours. FiO₂ levels for poractant alfa are consistently lower at every time point vs. beractant. At 15 minutes, mean FiO₂ levels are ~.50 for beractant and ~.45 for poractant alfa. At 30 minutes, mean FiO₂ levels are ~.45 for beractant and ~.41 for poractant alfa. At 1 hour, mean FiO₂ levels are ~.42 for beractant and ~.36 for poractant alfa. At 2 hours, mean FiO₂ levels are ~.37 for beractant and ~.32 for poractant alfa. At 4 hours, mean FiO₂ levels are ~.34 for beractant and ~.30 for poractant alfa. At 6 hours, mean FiO₂ levels are ~.33 for beractant and ~.28 for poractant alfa.³

P<0.05 at all post-treatment time points.

*Primary endpoint was FiO₂ AUC_0-6 defining onset of clinical response.

FiO₂ = fraction of inspired oxygen.

Adapted from Ramanathan R, et al. Am J Perinatol. 2004;21:109-119.

CUROSURF improves oxygenation within 5 minutes^1,2†

It has been suggested that faster oxygenation supports the treatment goal of weaning infants from mechanical ventilation more rapidly³

Oxygenation graph - see image description

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Line graph (adapted from Speer CP, et al. Arch Dis Child Fetal Neonatal Ed. 1995:72:F8-F13) showing arterial to alveolar oxygen tension ratio vs time in preterm infants with RDS treated with CUROSURF 200 mg/kg initial dose or Survanta 100 mg/kg initial dose (additional doses given if needed) at various time points, from 30 minutes to 6 hours, after randomization. The graph shows that initial treatment with CUROSURF 200 mg/kg resulted in greater improved oxygenation than Survanta 100 mg/kg. Between 5 minutes and 6 hours, infants receiving CUROSURF needed less oxygen than infants receiving Survanta (P<0.05 to 0.001).¹

^†Physiological end points (eg, faster reduction in FiO2) have not been proven to impact key clinical outcomes such as mortality due to RDS

^‡P<0.001.

^§P<0.01.

^¶P<0.05.

a/A PO₂ = arterial to alveolar oxygen tension ratio.

Adapted from Speer CP, et al. Arch Dis Child Fetal Neonatal Ed. 1995;72:F8-F13. Results from an open-label study. No short-term end points related to oxygenation were defined.

Study patients received rescue surfactant and mechanical ventilation as primary intervention. Early rescue INSURE technique not evaluated
CUROSURF is intended for intratracheal use only. The administration of exogenous surfactants, including CUROSURF, can rapidly affect oxygenation and lung compliance. Therefore, infants receiving CUROSURF should receive frequent clinical and laboratory assessments so that oxygen and ventilatory support can be modified to respond to respiratory changes

Dosing

In clinical studies, most infants required only one dose of CUROSURF, which may reduce complications associated with reintubation and subsequent mechanical ventilation (MV).^3,4

Clinical studies have not established that fewer doses result in superior safety or efficacy based on clinically relevant end points.

Single-dose success demonstrated across multiple studies^3,5,6

Limited need to redose may decrease the risks associated with reintubation and MV³

Single-dose graph- see image description

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Bar graph shows the percentage of patients not requiring a subsequent dose of CUROSURF or Survanta in multiple studies. In Dizder EA, et al, 2011, preterm infants with a median gestational age of 28 weeks (n=126), 88% of patients did not require a subsequent dose of CUROSURF, and 69% of patients did not require a subsequent dose of Survanta (P=0.023). In Karadag N, et al, 2014, 80% of preterm infants with a gestational age of less than or equal to 32 weeks (n=92) did not require a subsequent dose of CUROSURF, and 52% did not require a subsequent dose of Survanta. In Ramanathan R, et al, 2004, preterm infants with a median gestational age of 28.7 weeks (n=293), 73% of patients did not require a subsequent dose of CUROSURF; 51% of patients did not require a subsequent dose of Survanta.^3,5,6

^#Gestational age.

Sustained results with fewer doses

CUROSURF demonstrates consistent FiO₂ reductions sustained over time⁷:

Differences in FiO₂ over 48 hours vs Survanta (beractant)^7||

In a clinical trial, oxygen requirements did not rebound above redosing threshold (FiO₂ ≥0.30) after first dose of CUROSURF during the first 48 hours⁷
Sustained reduction of FiO₂ levels over 48 hours may reduce the need for redosing⁷

Sustained results graph - see image description

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Plotted line graph (adapted from Malloy CA, et al. Acta Paediatr. 2005;94:779-784) shows the differences in FiO₂ over 48 hours after receiving CUROSURF (poractant alfa) 200 mg/kg vs Survanta (beractant) 100 mg/kg at time points between 0 and 48 hours. Starting at ~1 hour, the FiO₂ requirements were lower with CUROSURF than with Survanta. The lower reductions in FiO₂ for CUROSURF vs Survanta were sustained over various time points between ~1 hour and 48 hours. Between hours 4 and ~26, the FiO₂ requirements for Survanta fluctuated within the .25 and .30 range, but after ~26 hours, they fluctuated within the .30 and .35 range. However, for CUROSURF, FiO₂ requirements stayed under .25 between hours ~4 and ~19 and hovered around ~.25 between hours ~20 and 48, except for upticks to ~.27 at time points of 30 hours and 36 hours.⁷

P=0.018 over first 48 hours.

^||Shading indicates FiO₂ range in which redosing was required.

FiO₂ = fraction of inspired oxygen.

Adapted from Malloy CA, et al. Acta Paediatr. 2005;94:779-784. (N=58)

Reductions in respiratory index over the first 3 days of life vs Survanta⁸

In a clinical trial, infants required lower respiratory support for the first 72 hours of life vs Survanta⁸

Reduction in respiratory graph - see image description

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Plotted line graph (adapted from Fujii AM, et al. J Perinatol. 2010;30:665-670) shows the differences in mean airway pressure x FiO₂ over 48 hours for CUROSURF (poractant alfa) vs Survanta (beractant) at time points throughout the patients’ first 72 hours of life. The MAP x FiO₂ was lower with CUROSURF than with Survanta for the duration of the study. Between the time points of ~9 hours and 72 hours, the MAP x FiO₂ values for Survanta stayed between 200 cm% and 300 cm%. For the same time points, CUROSURF values stayed at or below 200 cm%.⁸

P=0.032 over first 72 hours.

MAP = mean airway pressure.

Adapted from Fujii AM, et al. J Perinatol. 2010;30:665-670.

Lower respiratory requirements in the CUROSURF group could be attributed to a greater number of infants extubated at 48 and 72 hours vs Survanta⁸
Physiological end points (eg, faster reductions in FiO₂) have not been proven to impact key clinical outcomes such as mortality due to RDS

Volume

CUROSURF delivers more surfactant with less volume⁹**^,††

Initial dose delivers a higher concentration of surfactant at a lower volume vs other exogenous surfactants.^10-14 Less volume may improve tolerability and has the potential to reduce complications such as airway obstruction.⁹

CUROSURF delivers more surfactant with less volume^10-14

Initial dose delivers a higher concentration of surfactant at a lower volume vs other exogenous surfactants^10-14
Less volume may improve tolerability and has the potential to reduce complications such as airway obstruction^10-14

Image Description Collapse

Bar graphs show that CUROSURF (poractant alfa) intratracheal suspension delivered more surfactant with less volume than Survanta (beractant) and Infasurf (calfactant) intratracheal suspensions. The top bar graph shows the initial dose of surfactant delivery – CUROSURF: 200 mg/kg, Survanta: 100 mg/kg, and Infasurf: 105 mg/kg. The bottom bar graph shows the initial volume of surfactant – CUROSURF 2.5 mL/kg, Survanta: 4.0 mL/kg and Infasurf: 3.0 mg/kg.

**Clinical studies have not established that lower volume results in superior efficacy or safety based on clinically relevant end points^10-13
^††While clinical studies have demonstrated that phospholipids are an essential element, they have not established the quantity required for optimal surfactant efficacy^10-13
^‡‡The initial recommended dose of CUROSURF is 2.5 mL/kg birth weight. Up to 2 repeat doses of 1.25 mL/kg birth weight each may be administered at approximately 12‑hour intervals. A total of 4 doses of Survanta (4 mL/kg birth weight) can be administered no more frequently than every 6 hours in the first 48 hours of life. Infasurf (3 mL/kg birth weight) can be administered every 12 hours, up to a total of 3 doses.
^§§Based on a 1000-g infant and manufacturer’s dosing schedule. Volume of surfactant is measured in millimeters per kilogram of body weight at birth.

Distribution

CUROSURF spreads fast and evenly for smooth instillation^15¶¶

Control lamb: distribution in first 4 minutes

Quickly forms a stable surfactant monolayer inside alveoli¹⁶
Suctioning of airways permitted after 1 hour¹⁰

Distribution graphic - see image description

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A series of images shows the formation of surfactant monolayers inside the alveoli of a lamb lung. The surfactant monolayers are forming as early as 5 seconds, and the formation quickly accelerates at 15 seconds. At 2 minutes, the surfactant monolayers continue to intensify, and by 4 minutes, the monolayer is solidified and maintained.¹⁵

^¶¶Unpublished photos presented during the 15th International Workshop on Surfactant Replacement, 2000.

Preclinical data may not be predictive of clinical results

CUROSURF is a thin suspension that demonstrates a low reflux rate and fast recovery time after administration⁹

In an open-label, observational study, CUROSURF demonstrated relatively quick administration and rapid recovery within 1 minute.⁹ In addition, CUROSURF demonstrated a low reflux rate, which may improve tolerability and ease of administration⁹
It has been suggested that the thin suspension may help minimize airway and endotracheal tube obstruction and associated complications such as transient hypercapnia^9,17

3.5% reflux rate 5-15 min after administration (9).

81% of babies recovered within 1 min (9).

Image Description Collapse

The pie chart on the left shows that the reflux rate for CUROSURF 5 to 15 minutes after administration is 3.5%. The pie chart on the right shows that 81% of the preterm babies administered CUROSURF recovered within 1 minute.⁹

Adapted from Gerdes JS, et al. J Pediatr Pharmacol Ther. 2006;11:92-100.

^##It is important to note that the INSURE strategy may not be appropriate for all infants. Infants with RDS may vary markedly in the severity of respiratory disease, maturity, and presence of other complications, and thus it is necessary to individualize patient care.

IMPORTANT SAFETY INFORMATION

CUROSURF^® (poractant alfa) is intended for intratracheal use only. The administration of exogenous surfactants, including CUROSURF, can rapidly affect oxygenation and lung compliance. Therefore, infants receiving CUROSURF should receive frequent clinical and laboratory assessments so that oxygen and ventilatory support can be modified to respond to respiratory changes.

CUROSURF should only be administered by those trained and experienced in the care, resuscitation, and stabilization of preterm infants.

Transient adverse reactions associated with administration of CUROSURF include bradycardia, hypotension, endotracheal tube blockage, and oxygen desaturation. These events require stopping CUROSURF administration and taking appropriate measures to alleviate the condition. After the patient is stable, dosing may proceed with appropriate monitoring.

Pulmonary hemorrhage, a known complication of premature birth and very low birth-weight, has been reported with CUROSURF. The rates of common complications of prematurity observed in a multicenter single-dose study that enrolled infants 700–2000 g birth weight with RDS requiring mechanical ventilation and FiO₂ ≥ 0.60 are as follows for CUROSURF 2.5 mL/kg (200 mg/kg) (n=78) and control (n=66; no surfactant) respectively: acquired pneumonia (17% vs. 21%), acquired septicemia (14% vs. 18%), bronchopulmonary dysplasia (18% vs. 22%), intracranial hemorrhage (51% vs. 64%), patent ductus arteriosus (60% vs. 48%), pneumothorax (21% vs. 36%) and pulmonary interstitial emphysema (21% vs. 38%).

INDICATION

CUROSURF^® (poractant alfa) Intratracheal Suspension is indicated for the rescue treatment of Respiratory Distress Syndrome (RDS) in premature infants. CUROSURF reduces mortality and pneumothoraces associated with RDS.

Please see Full Prescribing Information.

References: 1. Speer CP, Gefeller O, Groneck P, et al. Arch Dis Child. 1995;72:F8-F13. 2. Collaborative European Multicenter Study Group. Pediatrics. 1988;82:683-691. 3. Ramanathan R, Rasmussen MR, Gerstmann DR, Finer N, Sekar K; And The North American Study Group. Am J Perinatol. 2004;21:109-119. 4. Verder H, Albertsen P, Ebbesen F, et al. Pediatrics. 1999;103:1-6. 5. Dizdar EA, Sari FN, Aydemir C, et al. Am J Perinatol. 2012;29:95-100. 6. Karadag N, Dilli D, Zenciroglu A, Aydin B, Beken S, Okumus N. Am J Perinatol. 2014;31:1015-1022. 7. Malloy CA, Nicoski P, Muraskas JK. Acta Pediatr. 2005;94:779-784. 8. Fujii AM, Patel SM, Allen R, et al. J Perinatol. 2010;30:665-670. 9. Gerdes JS, Seiberlich W, Sivieri EM, et al. J Pediatr Pharmacol Ther. 2006;11:92-100. 10. CUROSURF^® (poractant alfa) Intratracheal Suspension Prescribing Information, Chiesi USA, Inc. May 2021. 11.Survanta^® (beractant) Intratracheal Suspension Prescribing Information, AbbVie, Inc. October 2020. 12. Infasurf^® (calfactant) Intratracheal Suspension Prescribing Information, ONY, Inc, March 2018. 13. Moya FR, Gadzinowski J, Bancalari E, et al. Pediatrics. 2005;115:1018-1029. 14. Sinha SK, Lacaze-Masmonteil T, Valls I, et al. Pediatrics. 2005;115:1030-1038. 15. Ingimarsson J, Björklund L, Jonson B, et al. Biol Neonate. 2000;77(suppl 1):24. 16. Schürch S, Schürch D, Curstedt T, Robertson B. J Appl Physiol. 1994;77:974-986. 17. Wiseman IR, Bryson HM. Drugs. 1994;48:386-403.

Clinical Profile of CUROSURF

See the data:

Onset

Faster reduction in FiO2 requirements vs Survanta® (beractant)3*

CUROSURF improves oxygenation within 5 minutes1,2†

Dosing

Single-dose success demonstrated across multiple studies3,5,6

Sustained results with fewer doses

Differences in FiO2 over 48 hours vs Survanta (beractant)7||

Reductions in respiratory index over the first 3 days of life vs Survanta8

Volume

CUROSURF delivers more surfactant with less volume10-14

Distribution

CUROSURF spreads fast and evenly for smooth instillation15¶¶

CUROSURF is a thin suspension that demonstrates a low reflux rate and fast recovery time after administration9

Demonstrated success with early rescue INSURE##

Review dose preparation and handling of CUROSURF

Talk to a Chiesi representative

Faster reduction in FiO₂ requirements vs Survanta^® (beractant)³*

CUROSURF improves oxygenation within 5 minutes^1,2†

Single-dose success demonstrated across multiple studies^3,5,6

Differences in FiO₂ over 48 hours vs Survanta (beractant)^7||

Reductions in respiratory index over the first 3 days of life vs Survanta⁸

CUROSURF delivers more surfactant with less volume^10-14

CUROSURF spreads fast and evenly for smooth instillation^15¶¶

CUROSURF is a thin suspension that demonstrates a low reflux rate and fast recovery time after administration⁹

Demonstrated success with early rescue INSURE^##