vTv Therapeutics presented the findings of a pilot clinical study, now completed, evaluating TTP399, the company’s liver-selective glucokinase activator (GKA), an oral treatment being developed for patients with type 2 diabetes (T2D). Data were presented at the recent American Diabetes Association (ADA)’s 76th Scientific Sessions in New Orleans.
TTP399 is a small molecule compound designed to activate glucokinase (GK) in the liver without affecting the interaction between GK and GKRP (a protein produced in liver cells). The drug is now being evaluated for safety and efficacy in a Phase 2b study (AGATA, NCT02405260) that is expected to conclude in July.
In the poster, “TTP399, a Novel, Liver Selective Glucokinase Activator: Results from a 10 Day Pilot Study in Patients with Type 2 Diabetes Mellitus (T2DM) Naïve to Drug,” data demonstrated that the drug improved insulin resistance and glycemic control in treatment-naïve T2D patients. Treatment with TTP399 did not cause hypoglycemia or show unfavorable effects on plasma lipids.
“These results add to the body of preclinical and clinical evidence that support the potential of TTP399 for the treatment of diabetes,” Dr. Carmen Valcarce, senior vice president and chief scientific officer of vTv Therapeutics, said in a press release. “Dual-acting GK activators developed by others caused high rates of hypoglycemia and hyperlipidemia. We believe TTP399’s liver selectivity and preservation of the physiological regulation of GK — a unique attribute of our GKA— mitigates these side effects, making this compound potentially useful early in the disease in prediabetes or to intensify therapy without risk of hypoglycemia.
“We hope to confirm the efficacy and safety of this approach and to demonstrate the durability of the effect in our ongoing Phase 2b AGATA study,” Valcarce said.
AGATA is a randomized and placebo-controlled trial in 180 diabetes patients (on stable metformin doses), evaluating the effects of TTP399 on HbA1c (a measure of the average blood glucose) following six months of treatment. Top-line data from this trial are expected by mid-year.
Its primary endpoint is the change from baseline in HbA1c. Secondary endpoints include such safety measures as HbA1c levels of less than 7% following treatment, measures of plasma glucose, lipids [triglycerides (TG), total cholesterol, HDL cholesterol, and LDL cholesterol], insulin, lactate, C-peptide, glucagon, GLP-1, and body weight.
Data from pilot study, part of the TTP399 clinical development plan, reported results gathered from 16 patients with mild disease (A1c ≤ 7%), who were treated for 10 day with one of three doses levels of TTP399, compared to the placebo given to six patients (TTP339 at doses of 50 mg, 200 mg, or 400 mg were evaluated).
Researchers reported statistically significant improvements in insulin and glucose measures in patients receiving the two higher doses of TTP399, compared to those on placebo. Reported adverse events were similar between the treatment and placebo study arms.
vTv Therapeutics is also developing oral treatments for Alzheimer’s disease.