RZ358 is a potential intravenous monoclonal antibody in Phase 2 clinical development for Congenital Hyperinsulinism (CHI), an ultra-orphan indication. RZ358 is a first-in-class fully human antibody that counteracts the effects of elevated insulin (hyperinsulinemia) via allosteric modulation of the insulin receptor, making it well-suited as a therapy for severe, persistent hypoglycemia caused by hyperinsulinemic conditions such as CHI. XOMA demonstrated clinical proof-of-concept through Phase 2a studies and Rezolute plans to advance clinical development in 2018. The compound has received designated orphan status in the US and European Union.
CHI is a rare disorder in which the insulin-secreting cells of the pancreas (beta cells) fail to respond to normal regulatory controls, leading to inappropriate and excessive insulin secretion and action, including frequent episodes of severe hypoglycemia. In infants and young children, these episodes are characterized by lethargy, irritability and difficulty feeding. Repeated episodes of hypoglycemia increase the risk for serious complications such as breathing difficulties, seizures, developmental delays and intellectual disability, vision loss, brain damage, coma and possibly death. About 60 percent of infants with CHI experience a hypoglycemic episode within the first month of life. Other affected children develop hypoglycemia by early childhood. To avoid hypoglycemia, many require frequent glucose monitoring and feeding, including intravenous or intestinal administration of sugar solutions, particularly overnight. These necessities have a substantial negative effect on the quality of life of patients and their families, on top of the many morbidities caused by CHI. A significant number of patients cannot be adequately treated with or do not tolerate existing medical therapies. Surgical removal of all or part of the pancreas is a cornerstone of management for many patients, but is invasive and diabetes-inducing.