Every day of proper development is crucial for babies born prematurely, who often face significant health challenges due to their underdeveloped organs and systems.
This innovative therapy aims to strengthen the digestive system of preterm infants, helping them absorb nutrition more effectively and reducing their reliance on invasive medical interventions.
In this article, we will explore the significance of this breakthrough therapy, its key ingredients, the development process, and its potential impact on the lives of premature babies.
The Critical Need for Preterm Infant Care
Babies born prematurely, particularly those born before the 32nd week of pregnancy, face a multitude of challenges due to their underdeveloped organs and systems. One of the most pressing issues is the immaturity of their digestive tracts, which makes it difficult for them to break down and absorb essential nutrients.
The Threat of Necrotizing Enterocolitis (NEC)
NEC is a severe gastrointestinal condition that can cause inflammation, necrosis, and permanent disability in affected infants. Preterm babies with underdeveloped digestive systems are particularly vulnerable to NEC, and it remains a significant concern in neonatal intensive care units (NICUs) worldwide. Finding a solution to accelerate the development of premature infants’ digestive systems has been a long-standing challenge in neonatal medicine.
Elgan Pharma’s ELGN-GI Therapy
Insulin’s Role in GI Development
Insulin, aside from its role in regulating blood sugar, plays a vital role in stimulating a baby’s digestive tract to function after birth. In typical pregnancies, insulin is naturally produced in the GI tract during the mother’s third trimester, aiding in the development of the baby’s digestive system.
Additionally, breast milk from the mother contains insulin in the initial days following birth, further supporting GI tract maturation. However, preterm infants miss out on these critical sources of insulin, hindering their digestive system’s development. Elgan’s insulin-based therapy compensates for this deficiency by providing the necessary insulin to promote GI development.
Unique Formulation
Challenges in Developing the Therapy
Developing ELGN-GI was a challenging task, as few companies worldwide have ventured into this domain. The therapy’s approval process also faced unique hurdles, as the last drug approved specifically for neonates was in 1991. Neonatal intensive care units demand perfection in any medication designed for preterm infants, which increased the complexity of Elgan’s research and development efforts.
Positive Clinical Outcomes
Elgan Pharma’s groundbreaking therapy has already demonstrated impressive results in clinical trials. The highest-risk preterm infants who received the medication experienced an 80% reduction in the risk of developing NEC, a response unmatched by any other drug in previous trials.
A History of Research and Collaboration
The journey to ELGN-GI began over two decades ago when Prof. Naim Shahadeh of Rambam Health Care Campus and Prof. Raanan Shamir of Schneider Children’s Medical Center conducted pioneering research on insulin’s effectiveness in promoting GI development. Their initial studies in animals paved the way for the creation of Elgan Pharma, with Miki Olshansky as its founder and CEO. This collaboration between experts and visionaries culminated in the development of this life-saving therapy.
The Path Forward
Elgan Pharma, based in Nazareth, is committed to advancing neonatal care by addressing prematurity’s most pressing unmet medical needs. The company is currently preparing for its final clinical trial, involving over 400 preterm infants born between the 26th and 32nd weeks of pregnancy.
A parallel trial will also investigate the therapy’s impact on infants born before the 26th week of pregnancy. Regulatory approval from the United States’ Food and Drug Administration (FDA) is the next crucial milestone on Elgan’s journey.
Conclusion
Elgan Pharma’s innovative insulin-based therapy, ELGN-GI, represents a significant leap forward in neonatal medicine. By addressing the critical issue of underdeveloped digestive systems in preterm infants, this therapy has the potential to save lives and improve the quality of life for countless premature babies.
The commitment of Elgan Pharma’s founders and researchers, coupled with their groundbreaking results, underscores the immense promise of this therapy. As the company prepares for its final clinical trial, there is a growing sense of hope that ELGN-GI will revolutionize neonatal care and become a beacon of hope for the most vulnerable among us – premature babies born before their time.
in deep….
Enteral Administration of rh-Insulin in Preterm Infants: A Promising Approach to Enhance Intestinal Maturation and Early Feeding
Introduction
Preterm infants, especially those with a gestational age (GA) of 26 to 32 weeks, often face significant challenges related to their immature gastrointestinal systems, which can result in delayed achievement of full enteral feeding (FEF). In an effort to address this issue, a double-blind, placebo-controlled, randomized clinical trial was conducted to investigate the safety and efficacy of enteral administration of recombinant human insulin (rh-insulin) in preterm infants.
The Mechanism Behind Enteral rh-Insulin’s Beneficial Effects
The study built on previous research conducted in animals, which suggested that insulin plays a crucial role in promoting intestinal maturation. In both piglets and rats, enteral rh-insulin administration was found to increase small intestinal weight and intestinal disaccharidase activity, including lactase, sucrase, and maltase. These findings indicated that insulin’s impact on the intestine is mediated by insulin receptors located on both the apical and basolateral enterocyte membrane.
In humans, insulin receptor development on enterocyte membranes had been explored to a limited extent, revealing that up to 19 weeks of gestation, insulin receptors were present solely on the basolateral membrane. However, receptor expression on the apical enterocyte membrane during the third trimester of gestation or in intestinal tissues from preterm infants had not been previously investigated.
Positive Results in Preterm Infants
The study results demonstrated promising outcomes. Enteral rh-insulin administration significantly reduced the time needed to achieve FEF when compared to a placebo group in preterm infants with a GA of 26 to 32 weeks. Additionally, the study noted higher intestinal lactase activity in preterm infants receiving enteral rh-insulin, further supporting its potential benefits for intestinal maturation.
Study Design Considerations
Although the study yielded positive results, it is essential to consider the study design and limitations. A pilot study with a small sample size had shown positive results, but the sample size was limited, and the study design was not ideal. Therefore, additional research is necessary to thoroughly investigate the impact of rh-insulin on intestinal lactase activity in preterm infants.
The study also encountered challenges related to sample size estimation. The effect of enteral rh-insulin on time to achieve FEF was greater than anticipated, leading to an overestimation of the required sample size. This fortuitous outcome allowed the study to reach significant results despite being discontinued after enrolling 303 patients.
Futility Analysis and Dosing
Interestingly, the interim futility analysis, which included the first 225 randomized infants, suggested that both rh-insulin dosages were unlikely to reach significant efficacy. However, the final analysis, incorporating all randomized preterm infants, revealed statistically significant effects for both rh-insulin dosages. This discrepancy highlights the importance of setting appropriate stopping thresholds in future trials to prevent premature termination of effective interventions.
Regarding dosing, the study indicated that only the high-dose rh-insulin significantly reduced the time to achieve FEF and the duration of parenteral nutrition. This suggests that high-dose rh-insulin may be preferable for routine clinical practice. Nevertheless, further research is required to confirm these findings and explore potential long-term benefits, such as improved neurodevelopmental outcomes.
Safety Profile of Enteral rh-Insulin
One crucial aspect of the study was its focus on safety. Approximately 16% of the participants experienced one or more serious adverse events (SAEs), consistent with the expected rate in preterm infants of the specified GA range. Importantly, these SAEs were not attributed to enteral rh-insulin treatment. Furthermore, none of the infants developed insulin antibodies. Additionally, the number of hypoglycemic events was similar between the active-treatment groups and the placebo group, suggesting that enteral rh-insulin is not absorbed into the systemic circulation, despite its supraphysiological concentration in milk.
Conclusion
The results of this double-blind, placebo-controlled, randomized clinical trial suggest that enteral administration of rh-insulin is a safe and effective strategy for reducing the time required to achieve FEF in preterm infants with a GA of 26 to 32 weeks. The study’s findings highlight the potential role of insulin in promoting intestinal maturation, but further research is needed to validate the dosing regimen and investigate long-term benefits. Additionally, this study emphasizes the importance of setting appropriate stopping thresholds in clinical trials to avoid premature termination of effective interventions.
reference link : https://jamanetwork.com/journals/jamapediatrics/article-abstract/2789461#new_tab
