Handok, a South Korean pharmaceutical company, said Wednesday that its research and development partner Rezolute has announced the results of a Type B meeting held with the U.S. Food and Drug Administration (FDA) on June 17 regarding the Phase 3 clinical trial "sunRIZE" for congenital hyperinsulinism treatment RZ358 (ersodetug). Rezolute is a U.S. biotech company developing treatments for rare endocrine and metabolic diseases.
Rezolute had disclosed in December last year that while the frequency of hypoglycemic episodes decreased from baseline in the sunRIZE study, the primary endpoint was not met as the results did not show a statistically significant difference compared to placebo.
The latest meeting focused on the sunRIZE results and data from the ongoing open-label extension study. Rezolute suggested that study environment factors, including patient behavioral changes and measurement limitations, may have influenced the outcomes. Although the primary analysis at week 24 did not meet the threshold for statistical significance, the company explained that continuous glucose monitoring (CGM)-based analysis showed consistent and clinically meaningful reductions in hypoglycemia exposure time compared to placebo across the full trial period.
The company submitted data to the FDA on the potential impact of patient behavioral factors, evidence of pharmacological activity, CGM-based glycemic improvements, sustained glycemic improvements in the open-label extension study, and reduced use of existing treatments.
According to Rezolute, the FDA acknowledged that in diseases with diverse patient characteristics such as congenital hyperinsulinism, behavioral factors related to trial participation can influence outcomes. The agency also noted limitations of the self-monitoring of blood glucose (SMBG)-based hypoglycemia endpoint used as the primary measure.
Rezolute explained that the unblinded nature of the SMBG process, designed to ensure patient safety, may have led patients to identify their treatment group, potentially causing behavioral differences.
The FDA recommended submission of the clinical study report and analytical data. A determination on whether a regulatory filing is possible or whether additional data is needed is expected to follow. Rezolute plans to share updates after the FDA's review in the second half of this year.
"It is encouraging that not meeting the primary endpoint has not ruled out the next steps," Rezolute CEO Nevan Charles Elam said. "The path forward will be determined after further review."