Rezolute, a U.S. biotech company affiliated with HANDOK, failed to meet the primary endpoint in the global phase 3 clinical trial of its congenital hyperinsulinism (HI) treatment, RZ358 (ersodetug).
An efficacy signal was observed in the highest-dose group, but the placebo group also showed a larger-than-expected reduction in hypoglycemia, and statistical significance was not achieved.
Rezolute announced topline results from the global phase 3 clinical trial of RZ358 on the 11th (local time). The trial was conducted for a total of 24 weeks with three biweekly doses followed by maintenance at 4-week intervals. According to results released by the company, the number of hypoglycemic events decreased by about 45% in the 10 mg/kg cohort, confirming efficacy. However, as about a 40% reduction was also observed in the placebo group, the difference between the two groups was not statistically significant.
In the key secondary endpoint using continuous glucose monitoring (CGM), the "change in daily time in hypoglycemia," the 10 mg/kg cohort showed a 35% improvement over placebo, but it still fell short of statistical significance.
Regarding drug exposure, target concentrations were reached across all age groups. In the safety assessment, the overall profile was favorable, and the company said it "suggests the potential for RZ358 to be used in both pediatric and adult patients." However, two participants experienced severe hypersensitivity reactions, leading to early discontinuation of treatment. The most common adverse reaction was mild and transient hypertrichosis (increased hair).
Brian Roberts, chief medical officer (CMO) at Rezolute, said, "It is disappointing that we did not demonstrate the expected level of glycemic improvement, but some results merit further analysis," and added, "We will explore future development directions through discussions with the U.S. Food and Drug Administration (FDA) based on breakthrough therapy designation (BTD)."
Roberts added, "We are deeply grateful to the patients, their families, and the researchers who participated in the trial, and many patients are enrolling in the open-label extension study."
Rezolute is also conducting another phase 3 clinical trial (the upLIFT study) of RZ358 targeting tumor-induced hyperinsulinism in addition to congenital hyperinsulinism.
This trial is being conducted as a single-arm, open-label study, with topline results scheduled for release in the second half of next year. The FDA designated RZ358 as a breakthrough therapy for tumor-induced hyperinsulinemic hypoglycemia in May this year, and development has continued.
Rezolute is a U.S. biotech venture developing treatments targeting rare and metabolic diseases, and HANDOK holds the domestic commercialization rights for RZ358 and is collaborating across the development stages.