Rezolute Gets FDA Clearance for Phase 3 Study of RZ358 for Hypoglycemia from Tumor Hyperinsulinism

Rezolute, Inc. (Nasdaq: RZLT), a biopharmaceutical company specializing in advanced therapies for rare diseases, has announced that its Investigational New Drug (IND) application for RZ358 (ersodetug) to treat hypoglycemia in patients with tumor hyperinsulinism (HI) has been cleared by the U.S. Food and Drug Administration (FDA). The company is now preparing to launch a Phase 3 clinical study in the United States, with patient enrollment expected to begin in the first half of 2025. RZ358 is also undergoing a pivotal Phase 3 trial globally for congenital HI, with results anticipated in mid-2025.

“Treating hypoglycemia in patients with tumor HI is crucial for preventing severe health complications and improving the overall quality of life,” stated Brian Roberts, M.D., Chief Medical Officer at Rezolute. He emphasized the promising outcomes observed in patients treated with ersodetug through the company's Expanded Access Program, as well as the demonstrated safety and efficacy in clinical studies for congenital HI. Roberts believes that the FDA's clearance of the IND signifies the potential of ersodetug to address a substantial unmet medical need, bringing the company closer to a universal treatment for hypoglycemia caused by various forms of HI.

The upcoming Phase 3 study will be a double-blind, randomized, placebo-controlled trial involving 24 participants with inadequately controlled hypoglycemia due to tumor HI. Participants will be randomized in a 1:1 ratio to receive either 9 mg/kg of ersodetug per week or a matched placebo, in addition to their standard care. An open-label arm may also include up to 24 additional participants whose hypoglycemia is being managed with IV glucose in a hospital setting. After a 6-week pivotal treatment phase, all participants may opt to continue receiving ersodetug in an open-label extension. The primary endpoint will focus on the change in the frequency of moderate to severe hypoglycemia events as monitored by self-measured blood glucose levels. Secondary endpoints will include overall hypoglycemia events, time spent in hypoglycemia as monitored by continuous glucose monitoring, patient-reported quality of life, hospitalizations, and changes in glucose requirements for those in the open-label hospital setting.

Ersodetug is a fully human monoclonal antibody designed to bind to an allosteric site on the insulin receptor in key tissues such as the liver, fat, and muscle. This binding action counteracts excessive insulin receptor activation caused by insulin and related hormones, thereby correcting hypoglycemia. Ersodetug's mechanism allows it to potentially treat hypoglycemia across all forms of HI, whether congenital or acquired.

Tumor hyperinsulinism (HI) is a rare condition, often caused by islet cell tumors (ICTs) and non-islet cell tumors (NICTs), both of which result in hypoglycemia due to excessive insulin receptor activation. Insulinomas, a common type of ICT, lead to hypoglycemia by promoting the overproduction of insulin. NICTs, including hepatocellular carcinoma, can cause hypoglycemia by producing insulin-like substances such as IGF-2, which activate the insulin receptor. Due to the high morbidity and mortality associated with tumor HI, there is a critical need for effective hypoglycemia treatments. Ersodetug has demonstrated real-world benefits in patients with insulinoma and preclinical studies have shown it can mitigate IGF-2 and insulin-mediated insulin-receptor signaling.

Rezolute, Inc. is dedicated to improving outcomes for individuals suffering from hypoglycemia due to various forms of HI. Their antibody therapy, ersodetug, has shown substantial benefits in clinical trials and real-world applications for both congenital and tumor-induced HI.