Elgan Pharma Announces Positive Results from its Phase III Study of ELGN-GI in Preterm Infants for Treatment of Intestinal Malabsorption

NAZARETH, Israel, March 2, 2022 /PRNewswire/ -- Elgan Pharma, a late-stage clinical biopharmaceutical company focusing on innovative treatments for critical conditions in neonates, announced today outstanding results from a Phase III study evaluating the safety and efficacy of ELGN-GI, a proprietary enteral insulin formulation for the treatment of intestinal malabsorption, that causes feeding intolerance in preterm infants. The study results indicate an unprecedented improvement in gastrointestinal (GI) function and a reduction in related complications, including reduction in time until life threatening central line can be removed, reduction in hospital stay and a reduction in the number of life-threatening necrotizing enterocolitis (NEC) events. ELGN-GI was well tolerated, and no drug-related adverse effects were observed. The findings were recently published in JAMA Pediatrics.

"Feeding intolerance is a common condition among preterm infants due to immaturity of the gastrointestinal tract," commented Prof. Hans van Goudoever, former Division Chair of Pediatrics, Emma Children's Hospital Amsterdam UMC, Professor of Pediatrics and since 2022 Dean at the University of Amsterdam and Chief investigator of the ELGN-GI program. "Feeding intolerance prolongs dependence on parenteral nutrition which, in turn, is associated with increased risk of short- and long-term life-threatening complications. We are very excited to see the positive results of this trial, showing multiple clinical benefits for ELGN-GI in improving intestinal maturation and the wellbeing of preterm infants. I trust that ELGN-GI holds the potential to improve the lives of premature infants and neonates suffering from short bowel syndrome."  

"One out of ten babies is born premature. The challenge that faces us is developing new therapies for unique unmet medical needs of this special population," said Miki Olshansky, CEO of Elgan Pharma said. "We are confident that ELGN-GI will be an important therapy for premature infants given its remarkable consistent clinical data across several trials to date. We look forward to initiating our second Phase III trial for ELGN-GI in the second half of 2022 towards registration."

"In addition, we are on track to launching a Phase IIb clinical trial for ELGN-EYE, our second product candidate, for the treatment of pre-term infants' retinopathy of prematurity. In the past decades, there has been a lack of novel drugs specifically addressing infant health, and we are excited to be pioneers and propel this important underserved population forward with two promising additions," added Ms. Olshansky.

About the Phase III Study
The Phase III randomized, double-blind, placebo-controlled, multicenter study evaluated the safety and efficacy of ELGN-GI in preterm infants, born at 26-32 weeks, and weighing at least 500g. The study enrolled 303 infants across 46 sites in the US, Europe and Israel.

Participants were randomized to receive either low-dose ELGN-GI (400 μIU/mL, n=110), high dose (2000 μIU/mL, n=95), or placebo (n=98), treatment was administered for up to 28 days.

The primary endpoint was days to full enteral feeding (FEF), defined as intake of at least 150 ml/kg/day for 3 consecutive days (marking significant reduction in life-threatening risks).  Additional secondary outcomes were the number and percentage of infants reaching full enteral feeding within 6, 8, and 10 days of intervention, time to achieve an enteral intake of ≥120 mL/kg/day for three consecutive days, the number of days receiving parenteral nutrition, and growth rate.

Main Results:
Time to achieve full enteral feeding was significantly reduced in infants receiving either low-dose ELGN-GI (10.0 [7.0–21.8] days; n=94; p=.03) or high-dose ELGN-GI (10 [6.0–15.0] days; n=82; p=.001) compared to infants receiving placebo (14.0 [8.0–28.0] days; n=85). The proportion of infants who achieved full enteral feeding in the first 6, 8, and 10 days of intervention was significantly higher in both active-treatment groups compared to the placebo group. In addition, time to achieve an enteral intake of ≥120 mL/kg/day for three consecutively days was significantly reduced in both active-treatment groups compared to the placebo group. The number of days receiving parenteral nutrition (intravenous nutrition) was significantly lower in the high-dose group compared to the placebo group.

Necrotizing enterocolitis (Bell stage 2 or 3) occurred in seven (6%) infants in the low-dose group, four (5%) infants in the high-dose group, and ten (10%) infants in the placebo group. In the most fragile, susceptible gestational age population of under 28 weeks, the difference between groups is even more pronounced; the percentage of infants with NEC dropped from 19.6% in the placebo group to 12.2% in the low-dose group and to 4.3% in the high-dose group. The percentage of infants with late-onset sepsis (LOS) was reduced from 15% in the placebo group to 12% (20% reduction) in the low-dose group, and 11% (26% reduction) in the high-dose group. Overall, percentage of subjects with severe adverse events was reduced from 18.6% in placebo to 12% (36% reduction) in the low-dose group and to 11.4% (39% reduction) in the high-dose group. Reduction in severe complications and hospitalization all contribute to substantial reduction in hospital staff burden and associated costs. None of the infants developed serum insulin antibodies, further establishing treatment safety.

About ELGN-GI
ELGN-GI is a proprietary formulation of recombinant human insulin tailored for neonatal use, delivered orally and compatible with infants' nutrition. ELGN-GI improves gastrointestinal function, increases absorptive surface area and enhances adaptation, thereby reducing the need for intravenous feeding and life-threatening complications.

The novel formulation results in a highly soluble insulin powder for reconstitution, which allows for accurate, low doses, appropriate for preterm babies. It is compatible with both Mother's Own Milk (MOM) and infant formulas and contributes to gut rehabilitation with no systemic exposure to insulin.

About Gastrointestinal Complications in Preterm Infants
Preterm birth is a leading cause for infant mortality and morbidity, leading to a lengthy hospitalization and various morbidities. A major hurdle impeding healthy growth of preterm infants in the initial stages of treatment is immaturity of the gut leading to malabsorption of nutrients. It can also trigger life-threatening complications such as gut atrophy and NEC. Currently, there is no approved treatment for preterm intestinal malabsorption. Current management is by invasive, intravenous nutrition (parenteral nutrition), that bypasses the gastrointestinal tract. However, this leads to a high risk of infection, an increased burden on the liver and growth failure.

Every year, an estimated 15 million babies are born preterm (before 37 completed weeks of gestation), amounting to more than 10% of births worldwide. Preterm birth complications are the leading cause of death among children under 5 years of age, responsible for approximately 1 million deaths in 2015. In addition, premature birth is responsible for various morbidities, including retinopathy of prematurity (ROP) and other vision impairments, lung complications and intestinal malabsorption leading to various gastrointestinal complications, in particular Necrotizing enterocolitis (NEC).

Necrotizing enterocolitis (NEC) is the most common life-threatening gastrointestinal emergency experienced by premature infants in the newborn intensive care unit (NICU). It is a devastating gastrointestinal disease that is associated with severe sepsis, intestinal perforation, and mortality of up to 30% of babies with the condition. Approximately 12% of low birth weight babies suffer from NEC, and those who survive are often prone to short bowel syndrome and other complications leading to significantly impaired growth and poor long-term neurodevelopment.

The hospitalization time of premature babies born before week 32 is 50-70 days. NICU hospitalization alone easily exceeds $5000 per day in the US, and the annual cost of NICU stays in the US alone is estimated to be over $26 billion.

About Elgan Pharma
Elgan Pharma is a clinical stage, neonatology-focused biotechnology company, dedicated to developing safe, tailored therapies to address medical complications and developmental challenges that are common in babies born prematurely. The company's two leading programs are ELGN-GI for the treatment of preterm infant intestinal malabsorption and ELGN-EYE for treatment of preterm infants' retinopathy of prematurity, the number one cause of childhood blindness worldwide. The Company was established in the NGT3 technological incubator.

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SOURCE Elgan Pharma