Global, multi-center, repeat-dose, phase 2 study of RZ358 (ersodetug), an insulin receptor antibody, for congenital hyperinsulinism.

Summary

In a global open-label phase 2b study (n=23), add-on ersodetug produced dose-proportional PK, no dose-limiting toxicities, and marked reductions in hypoglycemia events (median −59%) and time in hypoglycemia (median −54%), with 48–84% event reductions at 6–9 mg/kg. Improvements extended to overnight hypoglycemia, with near-universal response.

Key Findings

• Median reductions from baseline: hypoglycemia events −59% (p<0.001) and time in hypoglycemia −54% (p<0.001) across pooled doses.
• At 6–9 mg/kg, hypoglycemia events decreased by 48%–84% and time in hypoglycemia by 61%–65% (p<0.05).
• Predictable, dose-proportional pharmacokinetics with no deaths, adverse drug reactions, withdrawals, or dose-limiting toxicities.

Clinical Implications

Ersodetug could become a genotype-agnostic therapy for cHI, potentially reducing reliance on pancreatectomy or off-label agents and improving safety of glycemic control, including overnight periods.

Limitations

• Open-label, nonrandomized design without a control arm
• Short 8-week treatment period limits long-term safety and durability assessment

Future Directions

Randomized controlled trials with longer follow-up to evaluate durability, safety, genotype-specific responses, and combination strategies with existing cHI therapies.