Rezolute Shares Tanks as Phase 3 Study in Congenital Hyperinsulinism Fails

Rare Daily Staff

Rezolute shares fell around 90 percent after the company reported its experimental therapy ersodetug failed to meet its primary endpoints in a phase 3 study in patients with congenital hyperinsulinism.

The primary endpoint assessed the change in the average weekly hypoglycemia events by self-monitored blood glucose. There was an approximate 45 percent reduction in hypoglycemia events observed at the top ersodetug dose, which was not statistically significant compared to the placebo group, which experienced a 40 percent improvement.

The study also did not meet its key secondary endpoint, which assessed the change in average daily percent time in hypoglycemia by continuous glucose monitoring. At the 10 mg/kg dose of ersodetug, an approximate 25 percent reduction in time in hypoglycemia was observed, which was not statistically significant compared to the placebo group, which increased by approximately 5 percent.

Congenital hyperinsulism (HI) is characterized by excess insulin secretion, which causes repeated episodes of low blood sugar, or hypoglycemia. The condition often goes unnoticed in infants, putting them at risk of complications from recurring hypoglycemic events, including developmental delays, seizures, coma, and even death.

Ersodetug is a fully human monoclonal antibody that binds allosterically to the insulin receptor to decrease receptor overactivation by insulin and related substances, such as IGF-2, in the setting of hyperinsulinism to improve hypoglycemia. 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.

At the study dose regimens of 5 and 10 mg/kg administered every other week for three doses, followed by every four weeks over the remainder of the 24-week treatment duration, ersodetug target drug concentrations were achieved across all age groups studied.

Safety observations from the study were generally favorable and, in the opinion of the company, support the safe use of ersodetug in pediatric and adult patients. Two of the study participants experienced serious hypersensitivity reactions, which led to early discontinuation of the study drug. The incidence of serious allergic reactions across the program is relatively low compared to biologic or monoclonal antibody treatments. The most commonly reported study adverse event in ersodetug-treated participants compared to placebo was hypertrichosis, which was generally mild and self-limiting.

“We are disappointed that the study did not demonstrate significant improvements in glucose-related endpoints relative to placebo, as well as for the patients and families living with congenital HI who urgently need new treatment options,” said Brian Roberts, chief medical officer of Rezolute. “At the same time, there are aspects of the results that merit additional investigation, and we are conducting a thorough evaluation to gain a better understanding of the study outcomes, which will inform our path forward. We intend to meet with the FDA under our Breakthrough Therapy designation to consider next steps for the program.”

Photo: Brian Roberts, chief medical officer of Rezolute