Rezolute's Phase 3 Trial for Congenital Hyperinsulinism Drug Fails to Meet Primary Endpoints
Key Insights
Rezolute's Phase 3 sunRIZE study evaluating ersodetug for congenital hyperinsulinism (search) failed to meet its primary and key secondary endpoints despite showing a 45% reduction in hypoglycemia (search) events at the highest dose.
The study found no statistically significant difference between ersodetug treatment and placebo, with the placebo group unexpectedly showing a 40% improvement in hypoglycemia (search) events.
Safety observations were generally favorable with hypertrichosis (search) being the most common adverse event, though two participants experienced serious hypersensitivity reactions requiring discontinuation.
Rezolute announced disappointing topline results from its Phase 3 sunRIZE study evaluating ersodetug in patients with congenital hyperinsulinism (search), with the trial failing to demonstrate statistically significant improvements over placebo despite showing clinical activity at the highest dose tested.
Study Results Fall Short of Statistical Significance
The Phase 3 sunRIZE study did not meet its primary endpoint, which assessed change in average weekly hypoglycemia (search) events by self-monitored blood glucose. While the top ersodetug dose of 10 mg/kg showed an approximate 45% reduction in hypoglycemia events, this was not statistically significant compared to the placebo group, which unexpectedly experienced a 40% improvement.
The study also failed to meet its key secondary endpoint measuring change in average daily percent time in hypoglycemia (search) by continuous glucose monitoring. At the 10 mg/kg dose, ersodetug demonstrated an approximate 25% reduction in time spent in hypoglycemia, but this was not statistically significant compared to placebo, which increased by approximately 5%.
Treatment Protocol and Drug Exposure
The study evaluated dose regimens of 5 and 10 mg/kg administered every other week for three doses, followed by every four weeks over the remainder of the 24-week treatment duration. Ersodetug achieved target drug concentrations across all age groups studied, indicating adequate drug exposure was not a limiting factor in the trial outcomes.
Safety Profile Remains Favorable
Safety observations from the study were generally favorable and support the safe use of ersodetug in both pediatric and adult patients, according to the company. Two study participants experienced serious hypersensitivity reactions that led to early discontinuation of the study drug. The incidence of serious allergic reactions across the program remains relatively low compared to biologic or monoclonal antibody treatments.
The most commonly reported adverse event in ersodetug-treated participants compared to placebo was hypertrichosis (search), which was generally mild and self-limiting.
Company Response and Next Steps
"We are disappointed that the study did not demonstrate significant improvements in glucose-related endpoints relative to placebo as well as for the patients and families living with congenital HI who urgently need new treatment options," said Brian Roberts, M.D., Chief Medical Officer of Rezolute. "At the same time, there are aspects of the results that merit additional investigation, and we are conducting a thorough evaluation to gain a better understanding of the study outcomes, which will inform our path forward."
The company intends to meet with the FDA under its Breakthrough Therapy Designation to consider next steps for the program. The majority of study participants have continued into the open-label extension part of the study.
About the sunRIZE Study
The Phase 3 sunRIZE study was a multi-center, randomized, double-blind, placebo-controlled, parallel arm study designed to evaluate the efficacy and safety of ersodetug in patients with congenital hyperinsulinism (search) ages 3 months to 45 years old who were experiencing continued hypoglycemia (search) on currently available standard of care.
The study enrolled 63 participants across more than a dozen countries worldwide, including U.S. patients. Eligible participants were randomized to receive either ersodetug at 5 or 10 mg/kg doses or matched placebo-control as add-on to existing standard of care.
Ongoing Development Programs
Rezolute's Phase 3 upLIFT study for tumor hyperinsulinism (search) continues, with topline results expected in the second half of 2026. Ersodetug is a fully human monoclonal antibody that binds allosterically to the insulin receptor to decrease receptor over-activation by insulin and related substances in the setting of hyperinsulinism, thereby improving hypoglycemia (search).