The United States Food and Drug Administration (FDA) has lifted the clinical hold on vTv Therapeutics' cadisegliatin program, allowing the company to resume its Phase 3 clinical trial for type 1 diabetes (T1D). The announcement comes after the company successfully addressed concerns that led to the hold in July 2024.
Cadisegliatin (TTP399) is being developed as a potential first-in-class oral adjunctive therapy to insulin for T1D patients. The drug is an oral, liver-selective glucokinase activator that has demonstrated favorable tolerability in over 500 subjects treated for up to six months.
Clinical Hold Resolution
The clinical hold, initially imposed on July 26, 2024, was prompted by the discovery of an unidentified chromatographic signal in a human absorption, distribution, metabolism, and excretion (ADME) study that could not be resolved using standard mass spectroscopy. vTv Therapeutics submitted a complete response letter concluding that the signal was an experimental artifact, leading to the FDA's decision to lift the hold as of March 14, 2025.
Importantly, no patients had been dosed in the CATT1 Phase 3 trial at the time of the clinical hold, and previous clinical studies had not revealed any significant safety concerns.
Protocol Amendment to Accelerate Development
vTv Therapeutics plans to submit a protocol amendment that will reduce the overall duration of the CATT1 trial from 12 months to 6 months. This strategic modification will maintain the original primary endpoint of measuring level 2 and 3 hypoglycemia rates at 6 months but eliminate the additional 6-month safety data collection period.
"We are pleased that the FDA has lifted the clinical hold on our cadisegliatin program and are eager to resume our Phase 3 trial," said Paul Sekhri, Chairman, President and Chief Executive Officer of vTv Therapeutics. "Importantly, we plan to submit a protocol amendment to reduce the time to topline data by 6-months, which will allow us to initiate our larger Phase 3 studies sooner to support our future New Drug Application (NDA) submission."
The protocol change is expected to expedite the collection of topline data, enabling the company to advance more quickly to the larger pivotal studies required for a future New Drug Application submission.
Mechanism of Action and Potential Impact
Cadisegliatin works by selectively activating glucokinase in the liver, increasing its activity independently from insulin. This mechanism supports the clinical investigation of improved glycemic control through enhanced hepatic glucose uptake and glycogen storage.
If approved, cadisegliatin would represent a significant advancement in T1D management as the first oral adjunctive therapy to insulin. The drug's potential to improve glycemic control while potentially reducing hypoglycemia risk addresses a critical unmet need in diabetes care.
Type 1 Diabetes Treatment Landscape
Type 1 diabetes affects approximately 1.6 million Americans and requires lifelong insulin therapy. Despite advances in insulin formulations and delivery systems, many patients struggle to achieve optimal glycemic control without experiencing dangerous hypoglycemic episodes.
Current adjunctive therapies for T1D are limited, with most requiring injection. An oral option like cadisegliatin could significantly improve treatment adherence and quality of life for patients while potentially reducing diabetes-related complications.
Looking Forward to Trial Resumption
The CATT1 Phase 3 trial will evaluate the effects of cadisegliatin on glycemic control and the incidence of hypoglycemia compared to insulin alone. With the clinical hold now lifted, vTv Therapeutics is positioned to advance this promising therapy through late-stage clinical development.
The company, traded on Nasdaq under the symbol VTVT, focuses on developing novel oral, small molecule drug candidates for chronic diseases, with cadisegliatin leading its clinical pipeline.
