Eiger BioPharmaceuticals, Inc., focused on the development and commercialization of therapies for rare diseases, announced that the European Medicines Agency (EMA) has granted orphan designation to exendin 9-39 for the treatment of non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS).

NIPHS describes a spectrum of acquired metabolic disorders characterized by inappropriately high insulin levels (hyperinsulinemia) and low blood glucose levels (hypoglycemia), which includes post-bariatric hypoglycemia (PBH). Eiger is developing a novel subcutaneously administered form of exendin 9-39 for patients who experience dangerously low postprandial (postmeal) blood glucose levels due to PBH, a rare and debilitating disorder with no approved treatment.

“Stanford researchers have demonstrated activity in two separate clinical proof-of-concept studies, first using an intravenous infusion of exendin 9-39 and more recently using subcutaneous injection of exendin 9-39 in patients with PBH. Exendin 9-39 prevented hypoglycemia and associated symptoms during oral glucose tolerance testing in patients with PBH,” said David Cory, president and CEO of Eiger. “A significant unmet medical need exists and exendin 9-39 represents the first potential targeted therapy for patients suffering from PBH. A phase 2 multiple ascending dose (MAD) study of subcutaneously injected exendin 9-39 in PBH patients is currently enrolling at Stanford and we look forward to reporting results.”

Insulin is the principal physiologic hormone secreted to control high blood glucose levels.  Abnormal increases in insulin secretion can lead to profound hypoglycemia (low blood sugar), a state that can result in significant morbidities, including seizures, brain damage, and coma. GLP-1 is a gastrointestinal hormone that is released postprandially from the intestinal L-cells. GLP-1 binds to GLP-1 receptors on the beta cells of the pancreas and increases the release of insulin. In patients with PBH, GLP-1-mediated insulin secretion is dysfunctionally exaggerated.

Exendin 9-39 is a 31-amino acid peptide that selectively targets and blocks GLP-1 receptors, normalizing insulin secretion by the pancreas, and thereby reducing postprandial hypoglycemia. Exendin 9-39 is being investigated as a novel treatment for PBH. A therapy that safely and effectively mitigates insulin-induced hypoglycemia has the potential to address a significant unmet therapeutic need for certain rare medical conditions associated with hyperinsulinism. Exendin 9-39 has never been approved or commercialized for any indication. The long-term efficacy and safety of exendin 9-39 has not yet been established.

Approximately 150,000-200,000 bariatric surgical procedures are performed each year in the United States, and another 100,000 are performed each year in Europe. The estimated prevalence of PBH is 30,000 in the United States and 25,000 in the European Union. As the number of bariatric surgeries to treat obesity and related comorbidities has increased, so too has the number of individuals who experience PBH, with symptoms typically developing 12 to 18 months following surgery. PBH can occur with a range of severity in post-bariatric surgery patients. Mild to moderate hypoglycemia may be managed largely through dietary carbohydrate restriction. Severe hypoglycemia is more common in patients who have undergone a Roux-en-Y procedure, which can result in refractory postprandial hyperinsulinemic hypoglycemia leading to devastating neuroglycopenic outcomes, such as loss of consciousness, seizures, coma, or death. Severe PBH can be debilitating with a significant negative impact on quality of life. There is no approved pharmacologic therapy.