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Pediatric and Adolescent Endocrinology

ORF10-06 - Ersodetug (RZ358) in Congenital Hyperinsulinism: Top-Line Results from a Global, Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 3 Study (sunRIZE)

Saturday, June 13, 2026
2:30 PM - 2:45 PM CT
Location: Room W183BC
Disclosure(s):
Huseyin Demirbilek, MD: Rezolute Inc.: Clinical Trial Investigator (), Consultant ()
Davelyn Eaves Hood, MD, MBA: Rezolute, Inc.: Employee (any industry) ()

Objectives/Study Aims
There is a dire need for better therapies for congenital hyperinsulinism (cHI), which causes life- and brain-threatening hypoglycemia. Ersodetug (Erso) is a fully human insulin receptor modulating mAb in development for congenital and acquired (insulinoma) forms of HI. sunRIZE is a confirmatory Phase 3 RCT evaluating the safety and efficacy of Erso in participants with cHI.

Methods
Eligible participants ≥3 months old with inadequately controlled hypoglycemia (≥3 self-monitored events/week [SMBG] and ≥8% time in hypoglycemia by CGM) despite standard-of-care (SOC) were randomized to receive Erso (5 mg/kg [n=18] or 10 mg/kg [n=20]) or placebo control (PBO; n=17) by 30 min IV infusion every 2 to 4 weeks (loading then maintenance) for 24 weeks add on to SOC, followed by an open-label extension (OLE). Study drug was administered in double-blind fashion and CGM was blinded (except for hypoglycemia alarm) in patients who were naïve to CGM at study entry. The initial 8 infant participants received Erso in open-label fashion. The pre-specified and hypothesis-tested primary and key secondary efficacy endpoints were the % change from baseline (BL) in SMBG events and CGM hypoglycemia time, analyzed using a mixed model of repeated measures. A planned sample size of 48 RCT participants (16 per arm) provided an 80% power to detect a 35% net of placebo difference (assumed SD =0.35) for at least one dose level (2-sided significance level of p< 0.05).

Results
63 participants were enrolled (including 55 in the RCT); 59 completed the pivotal period and continued into OLE. BL demographics and characteristics (including age [mean 3.4 years], gender [31F/32M], genotype [75% kATP], SOC therapy [95%; 46% on 2+] and hypoglycemia levels [12.6 events/wk; 19.1% time] were generally well-matched across the treatment groups. Erso was generally well tolerated; 4 participants discontinued due to AEs (3 allergic reactions; 1 hypertrichosis [reported in mild form in 36% Erso participants]). Consistent with drug levels and insulin biomarker changes, concordant reductions from BL in both hypoglycemia events (SMBG) and time (CGM) were observed with Erso but were only significant compared to PBO (p < 0.05) at Week 16 by CGM.

Conclusions
Although primary and key secondary glycemic endpoints were not met due to a significant study effect, results show target engagement, pharmacologic activity, and consistent trends of hypoglycemia reduction with Erso, across multiple endpoints. A divergence of perception and accompanying behaviors between treatment groups may have impacted patient-monitored glucose endpoints, which are simultaneously a safety lifeline in this patient population. These important impacts / potential ancillary benefits are still being evaluated. High OLE participation and retention suggest a favorable perception and may offer alternative ways to evaluate the potential benefit of Erso.