Diabetes mellitus is a metabolic disorder resulting from a defect in insulin secretion, insulin action, or both. A consequence of diabetes is chronic hyperglycemia (elevated levels of blood glucose) with disturbances of carbohydrate, fat and protein metabolism. Long-term complications of diabetes mellitus include retinopathy, nephropathy, neuropathy, and increased risk of cardiovascular disease.
It is estimated that nearly 70 percent of Type 2 diabetic patients (17-20 mm US patients) will develop diabetic peripheral neuropathy (DPN) over the course of their disease. DPN, a progressive and debilitating complication of diabetes, is nerve damage caused by chronically high blood sugar in diabetic patients. It leads to numbness, tingling, loss of sensation, and frequently pain in the legs, hands, and feet. DPN is a significant cause of morbidity and mortality, accounting for more hospital admissions than all other diabetic complications combined, and is responsible for more than 60 percent of nontraumatic limb amputations. The only treatment available for DPN are agents that treat symptoms of pain; no treatment is available to slow or arrest the underlying disease of DPN. A disease modifying agent could have significant clinical importance and BioNevia believes BNV-222 could eventually be used to treat a large portion of this diabetic population.
BVN-222 (diepalrestat choline) is a potential disease modifying, first-in-class treatment for slowing or arresting diabetic neuropathy, a progressive disease. BNV-222 is a cocrystal of epalrestat, an aldose reductase inhibitor (ARI). In long term studies (bibliography) epalrestat has shown efficacy when administered chronically in slowing or arresting progression of the nerve damage typical for patients with DPN. Aldose reductase is an enzyme normally present in many parts of the body, that functions by catalyzing one of the steps in the sorbitol/ polyol pathway responsible for the breakdown of glucose. In diabetics, aldose reductase activity increases as the glucose concentration rises, especially in those tissues that are not insulin sensitive, which include the lens of the eye, peripheral nerves and kidney. Sorbitol does not diffuse through cell membranes easily and therefore accumulates, causing osmotic damage which leads to retinopathy and neuropathy.
The company has completed enrollment on a 12-month Phase 2b clinical study for BNV-222 (clintrials.gov ) in 400 subjects with diabetic peripheral neuropathy. Patients will be evaluated for efficacy on DPN as well as assessments for visual acuity and diabetic retinopathy outcomes. The trial is fully recruited and results are anticipated in 2017. The goal of the development program is to establish a disease modifying effect of BNV-222 in this patient population by demonstration of prevention, delay, or reversal of diabetes-induced neuropathy, neuronal dysfunction and nerve conduction deficits. The company has a complete preclinical package, and Phase 1 data, and is ready to discuss the Phase 3 plan with the FDA and EMEA based on Phase 2 results. BioNevia has also gained regulatory buy-in within selected ex-US markets to initiate commercialization based on the Phase 2 outcome.