Q&A: Enrollment started in phase 2b study of bronchopulmonary dysplasia prevention drug

Key takeaways:

• There are no approved prevention drugs for bronchopulmonary dysplasia in extremely premature infants.
• A global phase 2b study has a target enrollment goal of 338 infants.
• Results are expected in late 2028.

A phase 2b study of OHB-607, an investigational drug for the prevention of bronchopulmonary dysplasia, is currently recruiting extremely premature infants, according to a press release from Chiesi Group.

With an enrollment goal of 338 infants, researchers plan to evaluate the difference in severe bronchopulmonary dysplasia (BPD)/mortality incidence between extremely premature infants receiving OHB-607 (Oak Hill Bio, Chiesi Group) plus standard neonatal care vs. standard neonatal care alone at 36 weeks postmenstrual age.

This study will also collect data on secondary outcomes and drug safety, according to the release.

To learn more about BPD, OHB-607 and the phase 2b study, Healio spoke with Victoria Niklas, MA, MD, chief medical officer at Oak Hill Bio, and Federico Bianco, PhD, global medical head of care at Chiesi Group.

Healio: What is BPD?

Niklas and Bianco: BPD is the most common disease complication of extremely premature infants, affecting 40% to 50% of infants born at less than 28 weeks of gestation. While the development of BPD is multifactorial, the degree of prematurity due to the extent of underdevelopment and poor functioning of the lung is the main factor that puts an infant at risk for developing BPD. Additional factors, including exposure to high oxygen levels and prolonged use of mechanical ventilation to support the poorly functioning lung, also lead to inflammation and scarring characteristic of BPD.

Infants that develop BPD are also at an increased risk for neurodevelopmental disability, prolonged hospitalization and other long-term respiratory morbidities, including pulmonary hypertension, asthma and even COPD, resulting in a lifelong impact on infants and families.

Unfortunately, the care practices necessary to sustain life after preterm birth result in direct and bystander injury to the developing lung, particularly in infants requiring high levels of oxygen therapy and invasive ventilation for extended periods. As insulin growth factor 1 (IGF-1), one of the most important growth factors supporting the growth and development of the lung during the last trimester of pregnancy, becomes deficient after extremely premature birth, replacing IGF-1 with OHB-607 after early birth has the potential to help the lung develop normally, reducing the need for respiratory support, which could, in turn, reduce the severity of BPD and its long-term outcomes.

Healio: What are the current treatment options clinicians use in premature infants with BPD?

Niklas and Bianco: As of today, there are no drugs approved to prevent or treat BPD. Therefore, OHB-607 could be the breakthrough for extremely preterm infants since lung surfactants were approved more than 30 years ago.

Neonatologists caring for infants with BPD currently rely on off-label medications such as diuretics and steroids that only target symptoms of BPD rather than preventing the development of disease.

Healio: What is OHB-607?

Niklas and Bianco: OHB-607 is the recombinant form of human IGF-1 complexed with its main binding protein (rhIGFBP-3). IGF-1 is a key driver of vital organs’ growth and gestational development, including the lungs, eyes and brain. Mothers are the primary source of IGF-1 for the developing fetus until about 30 weeks gestational age when the fetal liver takes over. As a result, infants born before 28 weeks of gestational age have low levels of IGF-1, which is believed to result in critical organs like the lung to fail to grow and develop normally.

Healio: Why is treatment with OHB-607 so important after an extremely premature birth?

Niklas and Bianco: As just said, mothers are the primary source of IGF-1 for the developing fetus until about 30 weeks gestational age. Therefore, extremely premature infants develop IGF-1 deficiency after their early birth relative to the corresponding IGF-1 levels they would encounter in utero. Longitudinal studies report an association between lower serum IGF-1 levels at birth in extremely preterm infants and an increased risk for BPD, retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), poor neurodevelopment and overall growth impairment.

Therefore, replacing IGF-1 with OHB-607 provides a rationale for restoring IGF-1 to levels that would have been present in utero and potentially support the normal growth and development of the lung and other vital organs, thereby reducing the risk for complications after extremely premature birth. OHB-607 could be a therapeutic breakthrough for extremely preterm infants since lung surfactants were first approved for respiratory distress syndrome over 30 years ago.

Healio: Before beginning this study, a phase 2a study took place. What were the main findings from the phase 2a study?

Niklas and Bianco: The primary endpoint of the phase 2a study was ROP, a leading cause of blindness in premature infants.

Although our phase 2a study did not meet its primary endpoint in ROP, it did show a trend toward improvements on other secondary endpoints related to complications of prematurity, including a statistically significant reduction in severe BPD and a trend in the reduction of severe IVH. In addition, the phase 2a study supported the feasibility of OHB-607 infusion and demonstrated an appropriate safety profile. Ultimately, the outcome of the phase 2a study provided the platform for the phase 2b study on BPD.

Healio: What are the inclusion and exclusion criteria for the phase 2b study?

Niklas and Bianco: The phase 2b clinical study is a multicenter, randomized, open-label, two-arm study designed to evaluate the efficacy and safety of OHB-607 compared with standard neonatal care for preventing BPD and other complications of prematurity.

Subjects must be between 23 weeks plus 0 days and 27 weeks plus 6 days gestational age, and infant and maternal informed consent must be obtained. Some exclusion criteria apply, including chromosomal abnormality, genetic disorder/syndrome and clinically significant neurologic disease.

For additional information, please visit https://clinicaltrials.gov/study/NCT03253263.

Healio: What is the primary endpoint for this study? What other outcomes do you plan to investigate in phase 2b?

Niklas and Bianco: The primary endpoint of the study is the reduction in the incidence of severe BPD or death by 36 weeks postmenstrual age compared with extremely premature infants receiving standard neonatal care alone.

The study will also evaluate the impact of OHB-607 on weaning from respiratory technology support through 12 months corrected age as a longer-term respiratory outcome measure, the impact on neurodevelopment as assessed by Bayley Scales of Infant Development, and the incidence of other complications of prematurity, including IVH (bleeding in the brain) and ROP (vision impairment and blindness).

The study will utilize a modified National Institute of Child Health and Human Development score to define BPD severity grading. This score will then be used to determine the correlation of severe BPD on other measures of chronic respiratory morbidity, mortality, neurodevelopment impairment and overall infant and caregiver well-being and functioning.

Healio: What are your hopes for the phase 2b clinical study? How will these findings possibly impact clinicians?

Niklas and Bianco: Advances in perinatal and neonatal care over the last decades, including prenatal steroids, optimized surfactant replacement therapy and increased use of less invasive respiratory support techniques, have improved the survival of extremely premature infants; still, no medicinal product has been approved to prevent BPD, the most common complication of prematurity and cause of chronic lung disease in infancy and across the lifespan.

We hope that phase 2b will demonstrate a statistically significant reduction of the primary endpoint, severe BPD or death at term-corrected age, with a corresponding decrease in the time it takes to wean an infant from respiratory technology support compared with infants receiving standard neonatal care. OHB-607 also has the potential to improve long-term outcomes such as neurodevelopment and infant and family well-being with an appropriate safety profile.

With these results in hand, we anticipate that clinicians could uniformly prescribe OHB-607 to prevent BPD and reduce other complications of prematurity in extremely premature infants. These diseases impact not only infants during hospitalization in the neonatal ICU in the weeks and months after birth but also across their lifespan. Therefore, the value of OHB-607 to infants, families and society will be enormous.

Healio: When can clinicians expect to see results from this study?

Niklas and Bianco: The study results are anticipated to be published online in the second half of 2028.

References:

• Jensen EA, et al. Am J Respir Crit Care Med. 2019;doi:10.1164/rccm.201812-2348OC.
• Kramer BW, et al. Paediatr Respir Rev. 2023;doi:10.1016/j.prrv.2023.05.001.
• Ley D, et al. J Pediatr. 2018;doi:10.1016/j.jpeds.2018.10.033.
• Oak Hill Bio and Chiesi Group announce first patient enrolled in the resumed phase 2b clinical study evaluating OHB-607 for the prevention of bronchopulmonary dysplasia, the most common cause of chronic lung disease in premature infants. https://www.prnewswire.com/news-releases/oak-hill-bio-and-chiesi-group-announce-first-patient-enrolled-in-the-resumed-phase-2b-clinical-study-evaluating-ohb-607-for-the-prevention-of-bronchopulmonary-dysplasia-the-most-common-cause-of-chronic-lung-disease-in-premature-i-302148908.html. Published May 17, 2024. Accessed July 10, 2024.
• Thébaud B, et al. Nat Rev Dis Primers. 2019;doi:10.1038/s41572-019-0127-7.