Ersodetug shows potential clinical activity in congenital hyperinsulinism, Phase 3 sunRIZE trial suggests
Presenter: Huseyin Demirbilek, MD, Professor, Hacettepe University Faculty of Medicine, Department of Pediatric Endocrinology, Sihhiye/Ankara, Türkiye
Ersodetug (RZ358) in congenital hyperinsulinism: top-line results from a global, multicenter, randomized, double-blind, placebo-controlled phase 3 study (sunRIZE). Presented June 13, 2026.
In patients with congenital hyperinsulinism, treatment with an insulin receptor-modulating monoclonal antibody led to consistent reductions in hypoglycemia across multiple measures, according to results of the phase-3 sunRIZE study presented at ENDO 2026.
However, the results with the study drug, ersodetug, did not achieve statistical significance for either the primary or key secondary endpoints at week 24, the end of the treatment evaluation period. The primary endpoint was the change from baseline in the average number of weekly hypoglycemic events, while the key secondary endpoint was the change from baseline in the percentage of time spent in hypoglycemia, as assessed by self-monitored continuous glucose monitoring.
Multicenter study of congenital hyperinsulinism patients with continued hypoglycemia
sunRIZE was a global, randomized, double-blind, placebo-controlled phase-3 trial that evaluated the efficacy and safety of ersodetug in patients with congenital hyperinsulinism who were experiencing continued hypoglycemia despite receiving the currently available standard-of-care treatment. The investigators enrolled 63 participants ages 3 months to 45 years (mean age 3.4 years) from more than a dozen countries, including the United States. Of the 63 participants, 59 completed the 24-week pivotal period and continued into the optional open-label extension.
During the first 24 weeks, eligible participants were randomized to receive either ersodetug 5 mg/kg, ersodetug 10 mg/kg, or placebo by intravenous infusion as an add-on to their existing treatment. Participants received the study treatment every 2 to 4 weeks. Investigators administered the study treatment in a double-blind manner, and continuous glucose monitoring data were blinded except for hypoglycemia alarms in participants who had not previously used continuous glucose monitoring. The initial eight infant participants received open-label ersodetug.
Potential therapeutic benefit seen for rare disorder
During the maintenance dosing phase of the study, the investigators observed larger and often nominally statistically significant glycemic improvements. They reported that ersodetug reduced both the average number of hypoglycemic events and the average percentage of time in hypoglycemia based on self-monitored continuous glucose monitoring from baseline. The reductions were statistically significant compared to values in the placebo group (P < .05) only at week 16, however.
The investigators suggested that differential perceptions of treatment benefit may have influenced glucose-monitoring and hypoglycemia-management behaviors, potentially confounding endpoints based on participant-monitored glucose data.
Ersodetug was generally well tolerated, with four participants discontinuing because of adverse events (3 allergic reactions; 1 hypertrichosis). Of the participants randomized to ersodetug, 36% experienced mild hypertrichosis.
The investigators concluded that ersodetug may have clinical activity in patients with congenital hyperinsulinism, a rare disorder associated with a high risk of severe neurologic complications and death. Treatment options for congenital hyperinsulinism are limited, and many patients have an inadequate response to standard therapy, which is frequently associated with serious side effects and poor tolerability.
Disclosures
Huseyin Demirbilek, MD, reported serving as an investigator and consultant for Rezolute Inc. which supported the trial. Davelyn Eaves Hood, MD, MBA, was an employee at Rezolute, Inc.
References
Demirbilek H, Dastamani A, VY D, et al. Ersodetug (RZ358) in congenital hyperinsulinism: top-line results from a global, multicenter, randomized, double-blind, placebo-controlled phase 3 study (sunRIZE). Presented at ENDO 2026, June 13, 2026, Chicago, IL.
Rezolute announces oral presentation of results from its phase 3 sunrize study of ersodetug in patients with congenital hyperinsulinism at the pediatric endocrine society annual meeting. Press release. https://ir.rezolutebio.com/news/detail/375/rezolute-announces-oral-presentation-of-results-from-its-phase-3-sunrize-study-of-ersodetug-in-patients-with-congenital-hyperinsulinism-at-the-pediatric-endocrine-society-annual-meeting?utm_source=chatgpt.com Accessed June 13, 2026.