FDA Lifts Partial Hold on RZ358 for Congenital Hyperinsulinism, Approves U.S. Inclusion in Phase 3 Study

Rezolute, Inc., a late-stage rare disease company, has received clearance from the U.S. Food and Drug Administration (FDA) to move forward with its investigational treatment RZ358 (ersodetug) for congenital hyperinsulinism (HI). This clearance removes previous partial clinical holds and allows the company to include participants in the United States in its ongoing global Phase 3 study named sunRIZE.

Ersodetug is a promising treatment for hypoglycemia triggered by congenital HI. The ongoing sunRIZE study is a pivotal Phase 3 trial designed to assess the safety and efficacy of this novel therapy. The study is multi-center, double-blind, randomized, and placebo-controlled, aiming to enroll participants from numerous countries around the world. The study focuses on individuals aged between 3 months and 45 years who suffer from poorly controlled hypoglycemia due to congenital HI.

The company plans to begin study start-up activities in the U.S. soon, and anticipates that participant enrollment will commence in early 2025. This inclusion will enable Rezolute to announce topline data from the study in the latter half of 2025.

Nevan Charles Elam, Chief Executive Officer and Founder of Rezolute, expressed his satisfaction with the FDA’s decision, noting that the FDA has permitted the trial to proceed at all doses and in participants as young as three months old. Elam also highlighted a significant point from the FDA’s review: the liver toxicity observed in specific rat strains is not applicable to humans. He emphasized that Rezolute is in a unique position to advance ersodetug in two Phase 3 rare disease programs in both the U.S. and globally.

Ersodetug is a fully human monoclonal antibody that targets a unique allosteric site on insulin receptors. This action helps to mitigate the effects of excessive insulin receptor activation by insulin and related substances such as IGF-2, thereby improving hypoglycemia management in hyperinsulinism cases. Given that ersodetug operates downstream from the pancreas, it holds potential to universally treat hypoglycemia resulting from any form of HI.

The sunRIZE study aims to enroll up to 56 participants across more than a dozen countries worldwide. By including U.S. participants, Rezolute hopes to strengthen the data set and potentially expedite the availability of this critical treatment for individuals suffering from congenital HI.

Rezolute is also advancing another Phase 3 study for a separate condition, tumor-associated HI, following recent FDA clearance. This positions the company to make significant strides in the treatment of rare diseases, particularly those involving hyperinsulinism.

In summary, the FDA’s removal of partial clinical holds on RZ358 allows Rezolute to progress its research in the U.S., bringing hope to patients with congenital HI. The sunRIZE study is a crucial step toward potentially providing an effective treatment for a condition that currently has limited therapeutic options. With the anticipated enrollment of U.S. participants, Rezolute is poised to make significant advancements in addressing this rare and challenging disease.