Diasome Announces Substantial Level 2 Hypoglycemia Event Reductions in its Phase 2b OPTI-1 Study of Hepatocyte Directed Vesicle Technology in Type 1 Diabetes
June 15, 2020
CLEVELAND – June 15, 2020 – Diasome Pharmaceuticals, Inc., a company developing hepatocyte directed vesicle (HDV) technology that can be added to any commercially available insulin to prevent hypoglycemia for people living with diabetes, today presented positive results from its Phase 2b OPTI-1 study of injectable HDV added to mealtime insulin in people with type 1 diabetes (T1D) at the American Diabetes Association’s 80th Annual Scientific Sessions.
Insulin induced hypoglycemia has become a significant barrier to maintaining normal blood glucose control in patients on insulin therapy, and there are no currently approved mealtime insulin therapies that have been shown to prevent hypoglycemia. According to “Modeling the Total Economic Value of Novel Type 1 Diabetes (T1D) Therapeutic Concepts,” a recent white paper by the JDRF, on average about 20% of people with Type 1 diabetes in the US experience one or more severe hypoglycemic (SH) events per year. The average treatment cost of a single SH event is estimated at more than $16,000, which translates into more than $5 billion in hypoglycemia treatment costs per year in the US, alone.
This open-label, multicenter OPTI-1 study was designed to evaluate the hypoglycemia prevention effect of Diasome’s liver targeting system for mealtime insulin, called Hepatocyte Directed Vesicles, or HDV, on A1C, hypoglycemia, and bolus and basal insulin dosing in adult type 1 diabetes subjects with baseline A1C levels between 6.5% and 8.5%. Subjects underwent a three-month run-in period on standard-of-care therapy followed by three months of treatment with HDV added to mealtime insulin in conjunction with optimized basal insulin doses.
A total of 61 T1D patients were enrolled at eight U.S. trial sites. Following a 90-day run-in period during which patients were treated with standard of care insulin therapy (Lispro/Degludec) and unblinded real-time continuous glucose monitoring (Dexcom G6 system), patients were randomized into one of two groups: 1) HDV added to Lispro in conjunction with a 10% reduction in Degludec (basal insulin), and 2) HDV added to Lispro in conjunction with a 40% reduction in Degludec. Within six weeks following initiation of HDV Lispro treatment, both treatment groups returned to their optimized, pre-randomization basal insulin dosing rates, but their lispro dosing rate increased slightly (from 0.21 units/kg/day to 0.24 units/kg/day).
Over the 90-day standard of care optimization period (pre-HDV Lispro treatment), Level 2 hypoglycemic events (defined as >15 continuous minutes of CGM readings below 54 mg/dL) decreased by 10.8% over a 24 hour period, 10.6% during daytime, and 20.9% at nighttime. Mean baseline A1C for the cohort was 7.3%, decreasing to 6.9% by the end of the randomization period. After switching to HDV Lispro for the second 90-day treatment period, patients experienced an additional 17.1% reduction in 24-hour events, 6.7% reduction in daytime events, and 25.2% reduction in nighttime events. Mean A1C for the group at the end of the HDV Lispro treatment period was 7.0%. Of particular importance, the Level 2 event reductions during HDV Lispro treatment were achieved despite an overall increase in mealtime insulin and total insulin dosing, and these improvements in hypoglycemia were achieved without an increase in mean daily glucose or A1C.
Ruth Weinstock, MD, PhD (Distinguished Service Professor and Division Chief of Endocrinology, Diabetes, and Metabolism in the Department of Medicine at SUNY Upstate Medical University, Syracuse, NY), an investigator in the OPTI-1 clinical trial, said “The reductions in hypoglycemic events, and especially the reduction in nighttime events, during the 90-day HDV-Lispro treatment period support the conclusion that HDV liver targeted mealtime insulin has the potential to help decrease time in hypoglycemia. The physiologic effect of pancreatic insulin on the liver is to reduce both hyperglycemia, due to mealtime liver glucose storage, and hypoglycemia, due to liver post-meal glucose release as the body requires glucose. The addition of the HDV liver targeting system to lispro appears to help restore this physiological insulin effect. We are looking forward to participating in Phase 3 trials of HDV Insulin in people with Type 1 diabetes.”
Diasome’s Chief Scientific Officer W. Blair Geho, MD, PhD stated, “In combination with the substantial Level 2 hypoglycemia reductions demonstrated in Diasome’s Phase 2b ISLE-1 trial, published in Diabetes Care in November 2019, the Level 2 event reductions from the OPI-1 trial provide further evidence of the physiological role of liver targeted mealtime insulin in patients with Type 1 diabetes. These two trials represent a significant technical achievement in modern insulin development, as they demonstrate that insulin directed to the liver at mealtime is actually hypoglycemia preventive. We are especially excited about the major reduction in nighttime Level 2 events during HDV Lispro treatment, as overnight hypoglycemia risk is a significant challenge in Type 1 diabetes care.”
Marc Penn, MD, PhD, Diasome’s Chief Medical Officer, added, “While Type 1 diabetes patients generally view their mealtime insulin as the riskiest form of insulin in terms of hypoglycemia, in people without diabetes insulin’s mealtime action on the liver is fundamental to the body’s natural hypoglycemia prevention mechanism. The fact that patients experienced fewer Level 2 events even though they increased their mealtime insulin dosing is very encouraging. The HDV liver targeting system is positioned to enable patients to use mealtime insulin to prevent both hyperglycemia and, now, hypoglycemia. Assuming successful Phase 3 trials, which we anticipate initiating in 2021, HDV Insulin could be the first ever approved mealtime insulin shown to physiologically prevent hypoglycemia.”
About Hepatocyte Directed Vesicle (HDV) Technology
HDVs are the most advanced technology designed to restore normal physiology and potentially offer protection against hypoglycemia for patients with diabetes. Only 20-50 nanometers in size, these two-layered microscopic discs are designed to bring insulin to receptors highly expressed by liver cells. Liquid HDV can be mixed with any commercially available insulin prior to administration and is compatible with any insulin delivery system.
About Type 1 Diabetes (T1D)
T1D is a chronic, auto-immune disease characterized by the inability of the pancreas to produce insulin, which leads to elevated blood sugar levels. Diabetes costs represent a large burden to both patients and the healthcare system. More than 1.25 million americans are living with T1D and there is no cure.
About OPTI-1
The 24-week, open-label, multiple dose trial is designed to assess the safety, tolerability and efficacy of hepatocyte directed vesicle (HDV) technology when added to rapid-acting mealtime insulin. All patients received insulin Lispro and Degludec during a 12-week run-in period. After completing the run-in period, patients were randomized to a treatment group of either HDV added to Lispro while continuing Degludec (dose reduced by 40%) or HDV added to Lispro while continuing Degludec (dose reduced by 10%) for 12 weeks of treatment.
About Diasome Pharmaceuticals, Inc.
Diasome’s hepatocyte directed vesicle (HDV) technology is the only pharmaceutical insulin additive being developed to prevent hypoglycemia by restoring normal liver physiology in patients with diabetes. HDV technology is a Phase 3-ready asset designed to improve the safety and efficacy of all insulins. For more information, visit www.diasome.com or follow us on Twitter.
*“Modeling the Total Economic Value of Novel Type 1 Diabetes (T1D) Therapeutic Concepts,” a recent white paper by the JDRF
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