Rezolute Updates on Phase 3 sunRIZE Study of Ersodetug for Congenital Hyperinsulinism Hypoglycemia Treatment

Rezolute, Inc., a company focused on developing therapies for rare diseases, has announced positive findings from a recent review conducted by an independent Data Monitoring Committee (DMC) of the open-label arm in its sunRIZE Phase 3 trial for the treatment of hypoglycemia caused by congenital hyperinsulinism (HI). The study specifically investigates the drug ersodetug.

The open-label segment involved eight infant participants aged between 3 months and a year. These participants were administered ersodetug at doses of either 5 or 10 mg/kg during a bi-weekly loading phase, which transitioned into a monthly maintenance phase. The DMC evaluated the safety and pharmacokinetics (PK) data to ensure the adequacy of the drug's dose for infants, affirming the safety and tolerability of ersodetug within this age group. Importantly, the DMC’s review did not extend to the glucose efficacy outcomes, as these remain blinded to the company.

The observations from the DMC's analysis confirmed that the levels of ersodetug in infants were comparable to the effective exposures observed in older children during the Phase 2b RIZE study. This validation supports the chosen dose regimen and allows for the enrollment of infants into the double-blind, placebo-controlled portion of the study.

Brian Roberts, M.D., Chief Medical Officer at Rezolute, expressed optimism over these initial outcomes. Highlighting the drug's promising safety profile, he noted the significance of the ongoing year for Rezolute, especially after receiving the FDA’s Breakthrough Therapy Designation for ersodetug. Roberts emphasized the company's commitment to advancing treatments for patients suffering from hyperinsulinism.

The U.S. study startup activities are progressing well, with site activations and participant enrollments anticipated soon. Completion of the study enrollment is expected in the second quarter of 2025, with topline results projected by the year's end. These timelines are contingent on the DMC's recommendations following an upcoming interim analysis (IA).

This IA is designed to evaluate the sample size required for the primary endpoint of hypoglycemia and to ensure statistical confidence in the study’s final outcomes. The IA will occur at the end of the current quarter, with results from the DMC expected early in the second quarter of 2025. The analysis could lead to one of three outcomes: termination of the study for futility, continuation of the study as planned, or an increase in sample size by 33% to boost statistical reliability, which would delay enrollment completion to late 2025 and push topline results to mid-2026.

Congenital hyperinsulinism is a significant cause of recurring hypoglycemia in children, often presenting within the first month of life. If not properly managed, it can result in severe neurological damage or death. In some cases, surgical intervention is necessary when medical management fails. Over half of the children affected by congenital HI require long-term treatment due to hypoglycemia that remains unmanageable with existing therapies.

Ersodetug, a fully human monoclonal antibody, works by binding to the insulin receptor, mitigating the effects of insulin receptor over-activation. This mechanism offers promise for treating hypoglycemia caused by both congenital and acquired forms of HI. The Phase 3 sunRIZE study, encompassing multiple international sites, aims to evaluate the efficacy and safety of ersodetug in patients aged from 3 months to 45 years who suffer from poorly controlled hypoglycemia due to congenital HI.