Diasome Pharmaceuticals, Inc.’s HDV liver targeting technology that may be added to any insulin met its primary endpoint when mixed with Lispro (HDV-L) of non-inferiority to Lispro (Eli Lilly’s Humalog®) in hemoglobin A1C (HbA1C) at 26 weeks in the InSulin Liver Effect (ISLE-1) Phase 2b clinical trial in patients with type 1 diabetes. Patients in this multi-center, 26-week, randomized, double-blind study received either HDV-L or Lispro as their mealtime insulin plus standard basal insulin therapy. Diasome presented these results at the American Diabetes Association’s 79th Scientific Sessions, June 7-11, 2019, in San Francisco, California.

David Klonoff, M.D., Medical Director of the Mills-Peninsula Medical Center Diabetes Research Institute – part of Sutter Health – and principal investigator of the study, commented, “Not only do the results meet the primary endpoint, they also demonstrate a clean safety profile and offer important insights into liver-targeted mealtime insulin’s effect on overall glucose control in people with type 1 diabetes. In patients with higher baseline HbA1C, HDV-L led to a HbA1C reduction equivalent to conventional Lispro treatment, but these HDV-L treated subjects reduced their mealtime insulin dose by 25% and experienced a trend towards a 73% reduction in time spent in hypoglycemia. Patients with lower baseline HbA1C levels did not change their bolus mealtime insulin doses and spent increased time in hypoglycemia. These results are consistent with the core hypothesis that improved liver glucose storage at mealtime should reduce both peripheral glucose exposure and peripheral insulin requirements.”

Key highlights of ISLE-1 include:

• In subjects with baseline HbA1C ≥8.5% treated with HDV-L there was a ~0.5% HbA1C decrease from baseline (comparable to control Lispro) with ~25% less bolus insulin used (p=0.02) and ~73% less time spent with blood glucose levels <54 mg/dL (p=0.09).
• In subjects with baseline HbA1C <8.5% treated with HDV-L, compared to Lispro, HDV-L was associated with no change in A1C or insulin dose over time and a >3X increase in time spent with blood glucose levels < 54 mg/dL.
  

Data from this study also confirmed key safety endpoints for liver-targeted HDV-L therapy, including no increase in liver enzymes and specifically no elevation of alanine transaminase (ALT) or aspartate transaminase (AST) values >3X the upper limit of normal from baseline to week 25 compared to conventional Lispro over six months of therapy. Patients treated with HDV-L also demonstrated a decrease in total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides, further supporting enhanced insulin action at the liver.

W. Blair Geho, M.D., Ph.D., Chief Scientific Officer, commented, “We are encouraged by the results of this first ever six-month study of a mealtime liver-targeted insulin. The analysis demonstrates the importance of optimally balancing peripheral and liver insulin requirements when the liver is more physiologically engaged. In light of the liver’s ability to store a significant amount of glucose for several hours after a meal when exposed to insulin, it is likely that dosing regimens with HDV will require customization as baseline HbA1C levels change. We are working to identify the optimized HDV-L dosing regimen for patients with lower baseline HbA1C levels in order to fully capture our technology’s clinical benefit. We began enrolling patients in March of this year in our Phase 2 OPTI-1 dose finding study, designed to provide additional dosing guidance in patients with baseline HbA1C values between 6.5% and 8.5%. We look forward to entering Phase 3 and moving closer to fulfilling our mission to substantially improve outcomes and restore quality of life for people with diabetes.”