Ersodetug for Refractory Hypoglycemia Due to Malignant Insulin-Secreting Tumors

Refractory hypoglycemia is common in malignant insulin-secreting tumors and is associated with substantial morbidity. Ersodetug is a fully human monoclonal antibody that allosterically attenuates insulin receptor signaling with the potential to treat various forms of hyperinsulinism (HI). We retrospectively report outcomes from compassionate use of ersodetug in eight individuals with refractory hypoglycemia due to tumor HI.

Ersodetug was administered intravenously at 6 or 9 mg/kg every 1-2 weeks initially, followed by a frequency of every 2-5 weeks, as appropriate. Glycemic, functional, and safety outcomes were analyzed.

Eight adults (4 M/4F; 24-74 years; Eastern Cooperative Oncology Group (ECOG) 1-3) received ersodetug for insulin-secreting tumors (metastatic insulinoma, n = 7; cervical neuroendocrine carcinoma, n = 1). No drug-related serious adverse events were observed. Most patients experienced improved glycemic control, including discontinuation of parenteral glucose in 6 of the 7 applicable patients (median, 4.5 days) and a 35.6% relative reduction from baseline in time in hypoglycemia (<70 mg/dL) by continuous glucose monitoring (mean 12.4% to 8.0%; pseudo-median paired change of -3.8 percentage points [90% CI, -8.2 to -1,1; P = 0.02). These glycemic improvements permitted hospital discharge and reductions in other antihypoglycemic therapies beyond glucose infusion rate (pseudo-median change, -2.5; 90% CI, -3.5 to -1.0; P = 0.02), with associated improvements in ECOG status. The median treatment duration with ersodetug (11.5 months, range 5-17) tended to correspond to patient lifespan in the setting of metastatic disease.

Ersodetug therapy resulted in reduced hypoglycemia burden, ability to discontinue parenteral glucose infusion, allowing discharge from hospital, use of fewer antihypoglycemic therapies, and improved ECOG performance status in individuals with severe, refractory tumor HI.