In a packed session at the 75th Scientific Sessions of the American Diabetes Association, the lead investigator told attendees how a matchstick-size device delivered exenatide, producing lower blood glucose levels.
A drug-delivery system that eliminates the problem of poor adherence could be “transformational” in helping patients with type 2 diabetes mellitus (T2DM) achieve lower blood glucose levels, according to the lead investigator of the phase 3 study presented Monday at the 75th Scientific Sessions of the American Diabetes Association (ADA).
Julio Rosenstock, MD, director of the Dallas Diabetes and Endocrine Center at Medical City, and clinical professor of medicine at University of Texas Southwestern Medical Center, Dallas, presented results involving ITCA 650, which uses a matchstick-size mini-pump implanted beneath the skin to deliver a continuous dose of exenatide, a GLP-1 receptor agonist previously approved by FDA. Dr Rosenstock presented results for FREEDOM-1, a placebo-controlled trial, whose overall results showed patients had an average reduction of 1.4% in glycated hemoglobin (A1C) at 39 weeks, with even better results for those not also taking sulfonylureas.
“A large part of the population remains inadequately controlled,” Dr Rosenstock told the packed session in Boston. While it is hard to say precisely how much of this is due to poor medication adherence, some health economists rate adherence as “good” when patients take medication only 80% of the time. ITCA 650, made by Intarcia Therapeutics, Inc., ensures 100% adherence and only requires that the mini-pump be replaced with a fresh supply of exenatide, typically every 6 months.
Throughout the weekend at ADA, attendees crowded the Intarcia booth in the exhibition hall to watch demonstrations of how the mini-pump works and is placed under the skin. ITCA 650 delivers therapy when a tiny engine fires a piston to continuously suspend the exenatide. While it is thought that the device will be replaced every 6 months, it can work for longer periods. “This can be easily done by a doctor, a physician’s assistant or a nurse practitioner,” Dr Rosenstock said at Monday’s session.
He said that the drug was well-tolerated; the most common adverse event was nausea, and results were consistent with other studies of drugs in the GLP-1 class. In general, patients have gastrointestinal issues when they start therapy, but these resolve over time.
Intarcia is also completing a study on cardiovascular effects, now required by FDA for new diabetes therapies, and filing is anticipated in 2016.
Results for FREEDOM-1.1 The placebo-controlled trial involved patients who started the study with glycated hemoglobin between 7.5% and 10%. Patients were randomized to daily exenatide doses of 40 mcg or 60 mcg, or placebo. For both groups receiving the study drug, patients received 20 mcg of exenatide for 13 weeks, then the higher dose for 26 weeks. Baseline characteristics were similar across all 3 groups, which totaled 460 patients: average A1C was 8.5%, BMI was 33.5 kg/m2, and the average duration of T2DM was 9 years.
At 39 weeks, average A1C reductions, compared with placebo, were 1.1% for patients taking the 40 mcg dose and 1.2% taking the 60 mcg dose. Patients who were not taking SUs saw an average A1C decline of 1.7%; most of these patients were taking metformin. According to the study abstract, patients taking the 60 mcg dose achieved more weight loss.
Higher-baseline patients.2 A separate study without a control group examined how well ITCA 650 would work for patients with A1C levels between 10% and 12%, “too high to risk randomizing them to placebo,” according to a statement from Intarcia.
In this study, 60 patients with a mean A1C of 10.8% and a mean BMI of 32 kg/m2 were given the study drug for 39 weeks, starting at the 20 mcg dose for 13 weeks and continuing at the 60 mcg dose for 26 weeks. Any oral antidiabetic drugs patients were taking prior to the study were continued.
These patients achieved an average A1C reduction of 3.4% at week 39, but researchers noted that significant reductions were seen by the 6-week mark; 22% of the patients saw reductions of 4% or greater, and 25% achieved A1C of <7%.
“I am very pleased with these phase 3 results,” said Robert R. Henry, MD, the study’s lead author, chief of Endocrinology and Metabolism at the VA in San Diego, and professor of Medicine in Residence, University of California at San Diego. The results show that this delivery method “may provide an uninterrupted, smooth and continuous dose that delivers powerful reductions in A1C without the need for patient action in terms of managing their medication, which we all know can be very challenging.”
1. Rosenstock J, Buse JB, Azeem R, Kjems S, Baron M. Clinical impact of ITCA 650 in type 2 diabetes: a randomized, double-blind, placebo-controlled 39-week trial. Diabetes. 2015; 64(suppl1) abstract 276-OR.
2. Henry RR, Rosenstock J, Denham DS, Prabhakar P, Kjems L, Baron M. Efficacy and tolerability of 39 weeks of ITCA 650 in poorly controlled T2DM with high baseline A1C. Diabetes. 2015; 64(suppl1) abstract 1107-P.