XOMA Corporation (Nasdaq:XOMA), a leader in the discovery and development of therapeutic antibodies, announced today it has initiated a Phase 2 proof-of-concept study to evaluate the safety and ability to prevent hypoglycemia (dangerously low blood sugar) of a single dose of XOMA 358 in patients with congenital hyperinsulinism (HI). XOMA 358 is a fully human allosteric monoclonal antibody that reduces insulin receptor activity.
HI is a genetic disorder in which the beta cells of the pancreas secrete excessive insulin that causes hypoglycemia, which can lead to brain damage or, in rare cases, death. HI is a rare disease, affecting approximately 1 in 50,000 newborns. The U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation to XOMA 358 for the treatment of HI.
"New treatments that safely and effectively attenuate insulin-induced hypoglycemia are needed for patients with congenital hyperinsulinism, as well as other diseases that cause hypoglycemia due to high insulin levels. There are no approved medications, and those currently used have inconsistent efficacy and issues with tolerability. Current disease management options are limited to continuous ingestion or infusion of glucose or surgical removal of part or all of the pancreas," said Paul Rubin, M.D., Senior Vice President, Research and Development, and Chief Medical Officer at XOMA. "We are developing XOMA 358 as a first-in-class therapeutic for patients with this potentially fatal disease, and we are pleased to be conducting this study at a world-class medical center recognized for its leadership in treating HI patients."
Proof-of-Concept Study Design
The open-label, single-administration study will evaluate XOMA 358 in congenital hyperinsulinism patients with documented hypoglycemia after a prolonged fast. Two cohorts of patients are planned, with the first cohort receiving a dose of XOMA 358 chosen based on the results from XOMA's Phase 1 study in healthy subjects. The second cohort of patients may receive a higher or lower dose dependent on the results seen in cohort 1. Patients will serve as their own control. The study will attempt to provoke and document hypoglycemic events due to fasting challenges prior to treatment with XOMA 358. Patients who experience hypoglycemia will be treated with XOMA 358 and then rechallenged by fasting at predetermined points in time to measure the potential impact and durability of XOMA 358 on hypoglycemia.
The study is open for patient enrollment at the Children's Hospital of Philadelphia (CHOP) and an additional international site is expected to open in the near-term. Safety will be monitored throughout the study. In addition, serial blood samples will be collected for pharmacokinetic and pharmacodynamic assessments. Various markers of drug activity will be assessed, including changes in glucose, ketones, insulin, C-peptide and free fatty acid levels. Controlled tests include monitored fasts, protein challenges, and oral glucose tolerance.
