Rezolute (RZLT) Study Result summary

Study design and execution

• Phase III Sunrise/sunRIZE study was a multi-center, randomized, double-blind, placebo-controlled trial evaluating ersodetug in congenital hyperinsulinism (HI) patients aged 3 months to 45 years, enrolling 63 participants across more than a dozen countries with high retention into an open-label extension.

• Participants received ersodetug (5 or 10 mg/kg) or placebo as an add-on to standard of care, with dosing every other week initially, then every 4 weeks for 6 months; dosing regimens were based on prior efficacy models and Phase II data, with target drug concentrations safely achieved.

• Patients were well-matched across treatment arms, with most on standard-of-care therapies and high baseline hypoglycemia rates.

• Primary endpoint was change in average weekly hypoglycemia events; key secondary endpoint was change in average daily percent time in hypoglycemia over six months.

• Safety profile was generally favorable; most common adverse event was mild, self-limiting hypertrichosis.

Efficacy results and interpretation

• Study did not meet the primary or key secondary endpoints; 45% reduction in hypoglycemia events at top dose vs. 40% in placebo, and 25% reduction in time in hypoglycemia at 10 mg/kg, neither statistically significant.

• Reductions in hypoglycemia events were similar across all arms, including placebo, with a strong placebo response complicating interpretation.

• Continuous glucose monitoring endpoints showed numerical improvements in active arms but did not reach significance due to variability.

• No changes in background therapies or tube feeds during the study; placebo effect attributed to patient and caregiver vigilance.

• Open-label extension is ongoing, with some patients weaned off other therapies and remaining on ersodetug monotherapy.

Safety and tolerability

• Safety profile was generally favorable, supporting safe use in pediatric and adult patients.

• Most common adverse event was mild, self-limiting hypertrichosis.

• Four patients discontinued due to adverse events, including two serious hypersensitivity reactions.

• Serious allergic reactions were relatively low compared to other biologics or monoclonal antibodies.