Diasome Pharmaceuticals today announced the online publication of its InSulin Liver Effect (ISLE-1) Phase 2b study results in respected clinician-focused journal Diabetes Care. The study investigated Hepatic Directed Vesicle (HDV) technology added to rapid-acting insulin in people with type 1 diabetes. The publication, authored by David Klonoff, MD, et al., is titled “The Divergent Hypoglycemic Effects of Hepatic Directed Prandial Insulin: A Six-Month Phase 2b Study in Type 1 Diabetes Mellitus.”

Robert Geho, chief executive officer of Diasome, commented, “We believe that HDV technology, an additive that is designed to be mixed with any commercially available insulin, has the potential to be the first insulin therapy that enables decreased hypoglycemia risk by delivering mealtime insulin to the liver and restoring more normal physiology.  Our enthusiasm is supported by the results of this clinical trial, which demonstrated HDV’s ability to simultaneously reduce HbA1c levels from baseline and decrease hypoglycemia risk in patients with high baseline HbA1c levels. If these results continue in our upcoming Phase 3 trial, patients taking insulin should benefit from not having to make a trade-off choice between lower HbA1c levels and less hypoglycemia risk.”

ISLE-1 was a 26-week, multi-center, randomized, double-blind, non-inferiority trial. HDV was mixed with insulin Lispro (Eli Lilly’s Humalog®) (HDV-L) and assessed in comparison to Lispro alone. Patients received either HDV-L or Lispro as their mealtime insulin plus standard basal insulin therapy. Across the entire study population, results demonstrated HDV-L to be non-inferior by means of change in HbA1c while significantly reducing total cholesterol, with no severe adverse events and no difference in liver function tests.

Subgroup analysis revealed different effects of mealtime HDV-L in patients with baseline HbA1c ≥8.5% versus <8.5%. Patients with higher baseline HbA1c levels treated with HDV-L experienced a similar ~0.5% drop from baseline in HbA1c compared with Lispro treated patients, but with ~25% less mealtime insulin used and ~73% less time in hypoglycemia, defined as blood glucose levels <54 mg/dL, than Lispro treated patients. Study subjects with lower baseline HbA1c levels treated with HDV-L saw no change in HbA1c or mealtime insulin dose, but spent increased time in hypoglycemia compared to Lispro treatment.  The authors concluded that the outcomes in both groups support the increased liver effect of HDV-L.

Dr. Klonoff, Medical Director of the Mills-Peninsula Medical Center Diabetes Research Institute and Clinical Professor of Medicine at UCSF, said, “We are encouraged to find that HDV-L met the study’s primary endpoint without liver toxicity or safety issues. The results are unique in the insulin clinical landscape because, for the first time, restoration of insulin delivery to the liver resulted in the simultaneous reduction in HbA1c over a 26-week period, reduced time spent <54 mg/dL as measured by blinded continuous glucose monitoring, and reduced pre-meal and total insulin dosing requirements in patients with HbA1c levels higher than 8.5% at baseline. We look forward to announcing results from our dose optimization study designed to provide additional dosing guidance in patients with baseline HbA1c values between 6.5% and 8.5% to maximize the amount of time these patients spend in target blood glucose ranges.”

The full publication can be accessed here.