Rezolute, Inc. has announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to ersodetug (RZ358) for the treatment of hypoglycemia due to congenital hyperinsulinism (HI). This designation aims to accelerate the development and review of ersodetug, a fully human monoclonal antibody, for this rare and potentially life-threatening condition.
The Breakthrough Therapy Designation was granted based on positive data from the Phase 2b (RIZE) study. The study demonstrated that ersodetug safely achieved significant improvements in hypoglycemia, with 75% or better reduction, in participants with congenital HI, without causing clinically significant hyperglycemia. Congenital hyperinsulinism is the most common cause of recurrent and persistent hypoglycemia in children, often presenting within the first month of life. These episodes, if not properly managed, can lead to brain injury and even death.
Clinical Development and Ongoing Studies
Ersodetug is currently being evaluated in a global Phase 3 sunRIZE study for congenital HI, with topline results expected in the second half of this year. Additionally, Rezolute anticipates initiating a Phase 3 study for tumor HI in the first half of 2025, with topline results expected in the second half of 2026. The FDA has also granted Orphan Drug Designation to ersodetug for the treatment of hypoglycemia due to tumor HI.
The Phase 3 sunRIZE study is a multi-center, randomized, double-blind, placebo-controlled, parallel arm study designed to evaluate the efficacy and safety of ersodetug in patients with congenital HI who are experiencing poorly controlled hypoglycemia. Participants between the ages of 3 months to 45 years old are eligible to participate, with the study enrolling up to 56 participants in more than a dozen countries around the world.
Mechanism of Action
Ersodetug is a fully human monoclonal antibody that binds allosterically to the insulin receptor, counteracting the effects of insulin receptor over-activation by insulin and related substances like IGF-2. This mechanism shifts over-signaling back into a more normalized range, improving hypoglycemia in the setting of hyperinsulinism. Because ersodetug acts downstream from the pancreas, it has the potential to be universally effective at treating hypoglycemia due to any congenital or acquired form of HI.
Management Perspective
"2024 was a transformative year for Rezolute, marked by important clinical milestones and solid progress in advancing our mission to address hyperinsulinism in all forms," said Nevan Charles Elam, Chief Executive Officer and Founder of Rezolute. "This Breakthrough Therapy Designation underscores the potential of ersodetug to make a meaningful difference for patients with hyperinsulinism. This year we are focused on finishing recruitment for sunRIZE and announcing topline results, as well as commencing our Phase 3 study for tumor HI."
Financial Position
Rezolute raised $73 million in June 2024, providing the financial resources needed to support its clinical programs and operational goals into Q2 2026. As of December 31, 2024, Rezolute's cash, cash equivalents, and investments in marketable securities totaled $105.3 million.
About Congenital Hyperinsulinism
Congenital hyperinsulinism (HI) is the most common cause of recurrent and persistent hypoglycemia in children. Patients with congenital HI typically present with signs or symptoms of hypoglycemia within the first month of life. These episodes can result in significant brain injury and death if not recognized and managed appropriately. More than half of children with congenital HI require long-term medical treatment for hypoglycemia that is not addressed by available therapies.
