Rezolute Updates FDA Review Status for Ersodetug in Congenital HI

Rezolute provided an update on the ongoing FDA review of data from its phase 3 sunRIZE study of ersodetug for congenital hyperinsulinism (HI), after the trial did not meet its primary endpoint of reducing hypoglycemia events compared with placebo, the company announced September 9, 2026.¹

Following a March 2026 meeting, FDA requested additional data focused on continuous glucose monitoring (CGM)-based outcomes, which Rezolute submitted in June 2026. The agency has since indicated it is still reviewing the submission to evaluate a potential regulatory path forward, without a specific timeline for feedback.¹

"We appreciate FDA's continued engagement and thorough review of the extensive body of data generated from the sunRIZE program," said Nevan Charles Elam, JD, CEO and founder of Rezolute, in a company press release.¹ "We remain committed to working with the agency to determine a path forward for ersodetug in congenital HI and address the significant unmet needs of patients and families living with this serious, rare disease."

What did the sunRIZE trial show?

sunRIZE (RZ358-301) was a phase 3, multicenter, double-blind, randomized, placebo-controlled trial that enrolled 63 participants ages 3 months to 45 years with congenital HI experiencing continued hypoglycemia despite standard-of-care therapy. Participants received ersodetug at 5 mg/kg, 10 mg/kg, or matched placebo added to existing standard of care. The trial did not meet its primary endpoint (weekly hypoglycemia events) or key secondary endpoint (percent time in hypoglycemia by CGM), with reductions from baseline that were not statistically significant compared with placebo at the week 24 evaluation window.¹

Larger, often nominally significant glycemic improvements versus placebo were observed throughout the maintenance dosing phase across numerous CGM-based endpoints, including 50% or greater reductions in average daily percent time in hypoglycemia and average weekly hypoglycemia events at both dose levels in some analyses.¹

What is the status of FDA's review?

At a March 2026 Type B meeting, FDA acknowledged challenges posed by behavioral factors in this patient population, including limitations of self-monitored blood glucose-based hypoglycemia measures, and requested additional data for independent review.¹ In June 2026, Rezolute submitted source and analysis datasets and summary results from pre-specified, post-hoc, and sensitivity analyses focused on CGM-based outcomes from the trial's pivotal portion. Because this review is occurring outside FDA's customary formal meeting process, no specific timeline exists for feedback or alignment on next steps, and Rezolute said it retains the ability to request a formal meeting if needed.¹

What longer-term data does Rezolute have?

An open-label extension phase of sunRIZE is ongoing, with high participant retention and cumulative ersodetug treatment duration ranging from approximately 9 months to more than 2 years, along with a reduction in background standard-of-care therapy use that the company said may indicate continued benefit with longer-term treatment.¹ In an earlier phase 2b trial of 23 patients, ersodetug (also known as RZ358) reduced hypoglycemia events by a median of 59% and time in hypoglycemia by a median of 54% compared with baseline, both statistically significant, with no deaths or study withdrawals reported.²

Why is a new treatment needed for congenital HI, and what's next?

Congenital HI is a rare, primarily pediatric disease caused by dysregulated insulin secretion that can lead to persistent, severe hypoglycemia and lifelong neurologic impairment. A UK-based study estimated a minimum incidence of about 1 in 28,389 live births.³ Ersodetug is a fully human monoclonal antibody that allosterically binds the insulin receptor to reduce overactivation by insulin and related substances, an approach Rezolute said has potential across multiple forms of hyperinsulinism.¹ Separately, the company is continuing to enroll patients in its phase 3 upLIFT trial of ersodetug for tumor HI and remains on track to report topline results before the end of 2026.¹

What are the limitations?

The sunRIZE trial did not meet its primary or key secondary endpoint, and the CGM-based improvements described come from post-hoc and sensitivity analyses rather than the trial's confirmed primary results. In addition, FDA has not indicated whether these data will be sufficient to support a regulatory path forward. No timeline for its decision has been provided.

References

1. Rezolute. Rezolute provides update on FDA review of its Phase 3 sunRIZE study results in congenital hyperinsulinism. Press release. Published September 9, 2026. Accessed September 9, 2026. https://ir.rezolutebio.com/news/detail/383/rezolute-provides-update-on-fda-review-of-its-phase-3-sunrize-study-results-in-congenital-hyperinsulinism
2. Demirbilek H, Melikyan M, Iotova V, et al. Global, multi-center, repeat-dose, phase 2 study of RZ358 (ersodetug), an insulin receptor antibody, for congenital hyperinsulinism. Med. 2025;6(6):100611. doi:10.1016/j.medj.2025.100611
3. Yau D, Laver TW, Dastamani A, et al. Using referral rates for genetic testing to determine the incidence of a rare disease: the minimal incidence of congenital hyperinsulinism in the UK is 1 in 28,389. PLoS One. 2020;15(2):e0228417. doi:10.1371/journal.pone.0228417