Rezolute Receives FDA Recommendation for Type B Pre-BLA Meeting for Ersodetug in Congenital Hyperinsulinism

Rezolute announced that the U.S. Food and Drug Administration (FDA) has recommended a Type B pre-BLA meeting ahead of a potential Biologics License Application (BLA) for ersodetug in hypoglycemia caused by congenital hyperinsulinism (HI).

The recommendation follows the FDA’s preliminary review of detailed data from the Phase 3 sunRIZE study. The agency did not provide an opinion on the approvability of ersodetug, noting that any such determination would be made during formal BLA review.

Phase 3 sunRIZE Study Missed Prespecified Endpoints

The Phase 3 sunRIZE study (NCT06208215) was a multicenter, double-blind, randomized, placebo-controlled trial evaluating ersodetug in congenital hyperinsulinism.

The study did not meet its primary endpoint, which assessed reductions in hypoglycemia events measured by finger-stick self-monitored blood glucose (SMBG). The reduction was not statistically significant compared with placebo.

The key secondary endpoint, which evaluated time spent in hypoglycemia using continuous glucose monitoring (CGM) during the Week 24 end-of-treatment evaluable window, was also not met.

Despite these results, Rezolute reported consistent and clinically relevant improvements across multiple CGM-based hypoglycemia measures in both treatment groups.

 FDA Reviewed Additional CGM Data

During a Type B meeting in March 2026, the FDA acknowledged challenges associated with clinical trials in congenital hyperinsulinism, including limitations of SMBG-based measures and behavioral factors that may influence outcomes. The agency requested the complete CGM dataset for independent review.

In June 2026, Rezolute submitted source and analysis datasets together with results from multiple prespecified, post-hoc and sensitivity analyses. Following its review, the FDA encouraged the company to request a pre-BLA meeting despite the study not meeting its prespecified primary and key secondary endpoints.

The recommendation represents continued regulatory engagement but should not be interpreted as an FDA finding of efficacy or approvability.

Open-Label Extension Shows Longer-Term Treatment Exposure

The open-label extension (OLE) of sunRIZE remains ongoing, with treatment exposure ranging from approximately nine months to more than two years. Rezolute has reported continued glycemic control and a reduction in the use of background standard-of-care therapies.

The company reported that all 59 participants who completed the controlled portion of the study elected to enter the OLE, with 56 participants remaining in the extension at the time of its September 2026 disclosure. These open-label observations may provide information on longer-term treatment effects but cannot independently establish controlled efficacy.

upLIFT Study Could Influence Regulatory Strategy

Rezolute is also evaluating ersodetug in tumor-related hyperinsulinism through the ongoing Phase 3 upLIFT study, with topline results expected later this quarter.

If the results support a regulatory submission, the company may seek an additional pre-BLA meeting and evaluate a broader BLA strategy covering both congenital and tumor-related hyperinsulinism.

Ersodetug Development Program

Ersodetug is a fully human monoclonal antibody that binds allosterically to the insulin receptor and reduces receptor overactivation caused by insulin and insulin-like growth factor 2 (IGF-2).

By acting downstream of pancreatic insulin secretion and paraneoplastic IGF-2 secretion, ersodetug is being investigated as a potential treatment for refractory hypoglycemia across multiple forms of hyperinsulinism.

The investigational therapy is being developed for congenital hyperinsulinism and tumor-related hyperinsulinism, including insulinoma and non-islet cell tumors, as well as hypoglycemia associated with bariatric and non-bariatric gastrointestinal surgery. Ersodetug has not been approved by any regulatory authority.

Regulatory Significance

The FDA’s recommendation for a Type B pre-BLA meeting marks an important regulatory milestone for Rezolute’s congenital HI program. However, the significance should be viewed in the context of the sunRIZE results, which did not meet either the prespecified primary or key secondary endpoint.

The upcoming pre-BLA discussions, together with topline results from the Phase 3 upLIFT study, will help determine Rezolute’s next regulatory steps for ersodetug. Whether the available evidence ultimately supports approval will depend on the totality of clinical and regulatory review.

 Reference

Rezolute Announces FDA Recommendation to Hold a Pre-BLA Meeting as a Precursor to Submitting a Biologics License Application (BLA) for Congenital Hyperinsulinism, Rezolute, 05 October 2026