EASD: First Injection-free Once-A-Year GLP-1

Intarcia Therapeutics, Inc. presented the results of the final 48-week results from a phase 2 clinical study of ITCA 650 (DUROS® subcutaneous continuous delivery of exenatide) for the treatment of type 2 diabetes.

The results of the phase 2 study were presented by Julio Rosenstock, M.D., Director of the Dallas Diabetes and Endocrine Center at Medical City and Clinical Professor of Medicine at the University of Texas Southwestern Medical School. The study demonstrated that patients receiving treatment with ITCA 650 experienced substantial and sustained reductions in HbA1c, fasting plasma glucose (FPG) and body weight during the 48 weeks of treatment at all doses. ITCA 650 20 mcg/day provided improved glycemic control with the most favorable tolerability profile as a starting dose for weeks 1 through 12. Subsequent transition to ITCA 650 doses of 40, 60 or 80 mcg/day led to statistically significant reductions in HbA1c, FPG and body weight after 24 and 48 weeks of treatment.  

The phase 2 study enrolled 155 type 2 diabetes patients (51-53 patients/arm) across 50 centers in the United States. Prior to study entry, patients were on a stable treatment regimen of metformin monotherapy that was continued throughout the study.  The study compared six different regimens of ITCA 650 to optimize dose and regimen for further evaluation in phase 3 studies.

After an initial 12-week treatment period comparing ITCA 650 20 mcg/day and 40 mcg/day with twice-daily injections of exenatide, patients continued treatment with one of 4 doses of ITCA 650: 20, 40, 60 or 80 mcg/day in the following manner through the planned 24-week endpoint:

Clinical sites were authorized to offer patients an extension of up to an additional 24 weeks of ITCA 650 treatment to evaluate longer term safety and durability of response. Among the sites participating in the extension phase, a total of 86 patients (85% of patients at these sites) elected to continue ITCA 650 therapy.

Sustained reductions in HbA1c, FPG and weight were observed across all treatment arms from week 24 through week 48. Reductions in HbA1c were greatest in the 60 mcg/day and 80 mcg/day dose arms but not statistically different between these two dose arms.

Based on the robust treatment response observed at the week-24 study endpoint and the durability of response observed at week 48, a starting dose of ITCA 650 20 mcg/day for weeks 1-12 followed by transition to ITCA 650 60 mcg/day appears to provide the greatest incremental reductions in HbA1c, FPG and body weight with the most favorable tolerability profile.

Throughout the extended treatment duration of the study, there were no treatment discontinuations due to nausea.  Numeric improvements were observed in measures of blood pressure and lipids at weeks 24 and 48 compared to baseline.

Study results indicated that patients receiving ITCA 650 at doses of either 20 mcg/day or 40 mcg/day experienced a statistically significant improvement in their quality of life after 8 weeks of ITCA 650 therapy compared with their level of satisfaction at study entry on oral metformin therapy. Patients on either dose of ITCA 650 also experienced a greater increase in their level of satisfaction with treatment compared with patients on twice-daily self-injections of exenatide.  Results of the week 20 assessment showed a statistically significant improvement in treatment satisfaction among patients switching to ITCA 650 from exenatide injection. The substantial improvement observed among patients initially randomized to ITCA 650 was maintained after transition to higher doses of ITCA 650.

In the same session, Intarcia's Chief Medical Officer, Kenneth L. Luskey, MD, presented an analysis of pharmacokinetics and pharmacodynamics from the ITCA 650 48-week phase 2 study.  Results of the analysis confirmed that treatment with ITCA 650 achieves steady state plasma levels of exenatide within 24-48 hours and provides continuous exposure and consistent plasma levels of exenatide for up to 48 weeks.  Following removal of ITCA 650, exenatide levels became undetectable within 24 hours.  Nearly all patients responded to ITCA 650, and greater reductions in HbA1c, FPG and body weight were observed among patients with the highest plasma exenatide concentrations.

The ITCA 650 phase 3 program, planned for late 2011 initiation, will evaluate treatment regimens involving initial 3-month ITCA 650 dosing at 20 mcg/day transitioning to 60 mcg/day and thereafter using ITCA 650 devices of both 6- and 12-month durations. See this week's Product of the Week for more information.

European Association for the Study of Diabetes (EASD) 47th Annual Meeting: Presented September 13, 2011.