For Patients

Congenital hyperinsulinism (cHI) is the most common cause of recurrent hypoglycemia in neonates and infants. The incidence of congenital HI is estimated at 1 in 28,000 live births throughout the world, but is as high as 1 in 2500 live births in certain populations where the gene pool is limited. Typically, cHI presents in the first month of life with non-specific signs and symptoms consistent with hypoglycemia. Over time, recurrent hypoglycemic episodes and/or dangerously low blood sugar levels can lead to progressive and irreversible brain damage and other health problems.  Fortunately, most patients with cHI survive into adulthood; however, even when on current standards of care, those who suffer with the disease may still experience hypoglycemia which can affect day-to-day functioning and lasting problems such as seizures, developmental delay and brain damage. While 14 different genetic defects have been found to cause cHI, more than one-third of the individuals who suffer with the disease have an unknown genetic cause.

The two most commonly used long-term medications, diazoxide and octreotide, are not Food and Drug Administration (FDA) approved for all forms of this condition and are often ineffective or cause intolerable side effects. In cases where cHI patients are unresponsive to medical management, surgical removal of a portion of the pancreas or the entire pancreas is required. In those with focal cHI (where only a small portion of the pancreas is affected), surgical removal of the specific affected area often results in a cure. In those with diffuse cHI (where the whole pancreas is affected), a near-total pancreatectomy is undertaken, but still about half of these children continue to have hypoglycemia and require ongoing medical treatment for cHI.

It is important to note that surgery is performed in the US, but in many other places in the world, medical management is the only treatment option.

Tumor HI may be caused by two distinct types of tumors: islet cell tumors (ICTs) and non-islet cell tumors (NICTs), both of which lead to hypoglycemia due to excessive activation of the insulin receptor. Insulinomas are the most common type of functional ICT and cause hypoglycemia because of over production of insulin. NICTs can cause hypoglycemia by producing and secreting insulin-like paraneoplastic substances such as IGF-2 or related variants that bind to and activate the insulin receptor. This form of hypoglycemia can occur in multiple tumor types including hepatocellular carcinoma, fibrosarcomas, and mesotheliomas, among others. The unique mechanism of action of RZ358 (ersodetug) to attenuate excess insulin receptor activation mediated by insulin and related substances makes the therapy a potential universal treatment for hypoglycemia resulting from any cause of hyperinsulinism.