FDA Lifts Clinical Hold on Rezolute's Ersodetug for Congenital Hyperinsulinism, Allowing US Trial Enrollment
Key Insights
The FDA has lifted the partial clinical hold on Rezolute's ersodetug, clearing the way for U.S. patients to participate in the Phase 3 sunRIZE trial.
The decision was based on follow-up toxicology studies that found liver toxicity observed in earlier rat studies was strain-specific and not relevant to humans.
Rezolute plans to begin enrolling U.S. participants in early 2025, with topline data from the global sunRIZE study expected in the second half of 2025.
The FDA has removed the partial clinical hold on Rezolute's RZ358 (ersodetug), a potential treatment for hypoglycemia (search) caused by congenital hyperinsulinism (search) (HI), paving the way for U.S. patients to participate in the global Phase 3 sunRIZE study. This regulatory decision marks a significant step forward in the development of a new therapy for this rare and challenging condition.
The partial clinical hold was initially implemented following historical data that indicated liver toxicity in laboratory rats treated with ersodetug. However, Rezolute conducted follow-up toxicology studies in May 2024, which found no liver issues. The FDA subsequently determined that the previously observed liver toxicity was specific to the rat strain used in the earlier preclinical studies and not applicable to humans.
sunRIZE Trial Details
The global Phase 3 sunRIZE trial is a multi-center, double-blind, randomized, and placebo-controlled study designed to evaluate the safety and efficacy of ersodetug in patients with congenital HI. Rezolute plans to commence study start-up activities in the U.S. and anticipates enrolling U.S. participants in early 2025. Topline data from the study is expected in the second half of 2025.
The trial will enroll patients aged three months to 45 years with congenital HI who are experiencing poorly controlled hypoglycemia (search). It aims to recruit up to 56 participants across multiple sites worldwide.
Ersodetug Mechanism of Action
Ersodetug is a fully human monoclonal antibody that binds to insulin receptors in the liver, muscles, and fat. By binding to a unique allosteric site on insulin receptors, ersodetug counteracts the effects of insulin receptor over-activation by insulin and related substances, such as IGF-2, thereby improving hypoglycemia (search) in patients with hyperinsulinism. Its mechanism of action, acting downstream from the pancreas, could potentially make it effective for all forms of HI.
Management Commentary
"We are delighted that the FDA has completely removed the partial clinical holds and are allowing us to proceed in the US at all doses and in participants as young as three months of age as part of our ongoing global study," said Nevan Charles Elam, founder and CEO of Rezolute. He further added, "Coming on the heels of our recent announcement of FDA clearance of a separate phase 3 study in tumor-associated hyperinsulinism, we are in the unique and fortunate position to be advancing ersodetug in two phase 3 rare disease programs in the US and globally."
Congenital Hyperinsulinism: An Unmet Need
Congenital hyperinsulinism (search) is a rare genetic disorder that affects approximately 1 in 25,000 to 50,000 births. It is characterized by the dysregulation of insulin secretion, leading to severe and continuous hypoglycemia (search). If left untreated, it can result in brain damage, seizures, learning difficulties, cerebral palsy, blindness, and even death. Current treatment options include surgical removal of the pancreas or medications.