Intarcia Therapeutics, Inc., has announced top-line results from its FREEDOM-CVO trial, which evaluated the cardiovascular (CV) safety of ITCA 650, a matchstick-size, subdermal osmotic pump that delivers exenatide for the continuous control of type-2 diabetes. The trial met its primary and secondary endpoints and succeeded in delivering the clinical results necessary for regulatory filings.
Exenatide, the active agent in ITCA 650, is a glucagon-like peptide-1 (GLP-1) receptor agonist currently marketed globally as twice-daily and once-weekly self-injection therapies for type-2 diabetes. When approved, ITCA 650 will be the first injection-free GLP-1 therapy that can deliver up to a full year of treatment from a single placement of the osmotic mini-pump.
The FREEDOM-CVO Safety Trial was the fourth and final phase 3 clinical trial of the FREEDOM program. It was a global, placebo-controlled cardiovascular outcomes study designed to meet the preapproval safety assessment requirements set out in the FDA’s guidance for industry to evaluate cardiovascular risk for new therapies to treat type-2 diabetes. The trial evaluated the safety of ITCA 650 at 60 mcg per day versus placebo in just over 4,000 patients on a variety of approved standard-of-care antidiabetes therapies.
The duration of study was dependent on event-based outcomes, and lasted just under three years, reaching the target number of cardiovascular (CV) events in the fourth quarter of 2015. The average treatment duration was 1.2 years. Age eligibility for the study was 40 years and older. Inclusion criteria stipulated patients must have HbA1c over 6.5%, a history of coronary, cerebrovascular, or peripheral artery disease, or multiple CV risk factors.
The primary objective was to conduct a meta-analysis across FREEDOM-CVO and other phase 3 studies to demonstrate that the upper limit of the 95% confidence interval of the hazard ratio of major adverse cardiac events (MACE) in adult patients on standard of care for type-2 diabetes receiving either ITCA 650 or placebo did not exceed 1.8. There were a total of 160 strict MACE events observed in the trial. The overall safety and tolerability data for ITCA 650 were consistent with the three phase 3 trials that have already been presented and what is documented in the published literature for exenatide and other GLP-1 receptor agonist therapies.
Intarcia is also preparing to conduct additional head-to-head superiority studies against market-leading oral and injectable medicines. Some of the comparative trials will start this year, while other trials are planned to start with payers after approval to evaluate the relative performance of ITCA 650 versus other type-2 diabetes therapies in “real-world” settings, where poor adherence and poor control with pills and self-injections are best assessed.
Source: Intarcia Therapeutics, Inc.; May 6, 2016.