vTv Therapeutics Inc. (NASDAQ:VTVT) today announced positive results from Part 2 of the Phase 2 Simplici-T1 trial assessing TTP399 as an oral adjunctive therapy to insulin in adults with type 1 diabetes (T1D). TTP399 is a novel, liver-selective glucokinase activator taken once a day. The 12-week trial investigated the efficacy and safety of 800 mg of TTP399 compared with placebo in 85 people with type 1 diabetes on optimized insulin therapy. The study was conducted with support from JDRF International (JDRF), the leading provider of T1D research funding globally.
The trial successfully achieved its primary objective analyzed using two statistical approaches to evaluating the effect of TTP399. The primary statistical analysis evaluated the effect on HbA1c regardless of treatment adherence or notable changes in insulin administration. Under the primary statistical analysis, the trial achieved its primary objective by demonstrating statistically significant improvements in HbA1c (long-term blood sugar) for TTP399 compared to placebo at week 12 (p=0.03).
TTP399 was well tolerated with similar incidences of treatment-emergent adverse events overall and by system organ class in both treatment groups. The study had no report of diabetic ketoacidosis in either treatment group. There was no incidence of severe hypoglycemia in the treated group and one incident in the placebo group. Patients taking TTP399 experienced fewer symptomatic hypoglycemic episodes: two subjects taking TTP399 reported at least one event compared to eight subjects taking placebo.
“I am very pleased that part 2 of the study confirmed the positive results and effects we saw in part 1. A once-a-day pill that reduces HbA1c and improves time in range with continuous glucose monitoring, without increasing hypoglycemia or any signal for adverse events, is a big win for the future care of type 1 diabetes,” said Dr. John Buse, Director of the North Carolina Translational and Clinical Sciences Institute and of the Diabetes Center at the University of North Carolina School of Medicine and principal investigator for this study.
To eliminate the possibility that the reduction in HbA1c was driven by the administration of excess insulin (3 or more units per day), a second estimand analysis was performed.1 Based upon this analysis, people treated with TTP399 achieved a statistically-significant placebo-subtracted reduction in HbA1c of 0.32% (p=0.001). Patients taking TTP399 experienced a 0.21% reduction in HbA1c, while patients taking placebo experienced a 0.11% increase in HbA1c, from a mean study baseline HbA1c of 7.6% following a multi-week insulin optimization period prior to the administration of study treatment.
Daily Time in Range was improved by approximately two hours in patients treated with TTP399 relative to placebo (p=0.03). TTP399 treatment reduced the total daily mealtime bolus insulin dose by 11% relative to baseline (p=0.02) whereas the placebo-treated group experienced a 3% decrease relative to baseline.
“The development of a safe and effective therapy that improves glucose control is a critical step toward eliminating the dangerous highs and lows associated with type 1 diabetes,” said Sanjoy Dutta, Ph.D., JDRF Vice President of Research. “The results from the Simplici-T1 trial indicate that TTP339 is a promising oral treatment option to help people with type 1 diabetes keep their HbA1c levels within a healthy range, and stay in a desirable glucose range for most of the day, while simplifying the daily management of the disease.”
Despite advances in insulin and its administration, people with T1D continue to have difficulty achieving optimal glucose control (HbA1c of less than 7.0%), warranting the need for adjunctive therapies. TTP399 selectively activates glucokinase (GK), a key regulator of glucose metabolism, in the liver. This activation has been shown to increase glucose utilization, which in turn lowers blood glucose. Simplici-T1 is the first study to test activation of GK in patients with T1D, evaluating daily oral TTP399 as an adjunct to insulin therapy.
“Roughly 1.5 million people in the US are living with type 1 diabetes and the burdensome, around the clock disease management it requires to avoid life-threatening complications. These patients and their families are demanding new treatment options that offer simple, predictable diabetes management to improve HbA1c and time in range. Consistent with FDA guidance, a 0.3% improvement in HbA1c is considered clinically meaningful, and coupled with the well-controlled population of patients and favorable safety data from our clinical trials to date, this provides a strong basis for moving this potential first-in-class program forward,” said Steve Holcombe, President and CEO of vTv Therapeutics. “We intend to engage with the FDA as soon as possible to plan an efficient development pathway for TTP399 and hope to initiate a registration trial this year.”