Intarcia Therapeutics, Inc. presented today final results of a 24-week phase 2 clinical study of ITCA 650 (DUROS® continuous subcutaneous delivery of exenatide) for the treatment of type 2 diabetes at the 46th Annual Meeting of the European Association for the Study of Diabetes in Stockholm, Sweden.
Results of the phase 2 study demonstrated substantial reductions in HbA1c and body weight during the 24 weeks of treatment with ITCA 650 at all doses. A starting ITCA 650 dose of 20 mcg/day for weeks 1 through 12 provided effective glycemic control with the best tolerability profile. A transition to ITCA 650 at 60 mcg/day for weeks 13 through 24 was well tolerated and provided substantial incremental reductions in both HbA1c and body weight at week 24. An ITCA 650 treatment regimen involving a 20 mcg/day starting dose with a transition to 60 mcg/day after week 12 has been selected for a phase 3 clinical trial, anticipated to begin enrollment in early 2011.
"We are very encouraged by the results observed in this study and the high level of enthusiasm expressed by patients and investigators," said Kurt Graves, executive chairman of the board for Intarcia. "ITCA 650 is a novel therapeutic approach for type 2 diabetes that holds new promise for many patients and physicians who want highly effective glucose reductions and weight loss without the tradeoff associated with having to start potentially lifelong and frequent self-injections." Graves added, "ITCA 650 also holds the promise to ensure patient compliance and long-term control given the breakthrough nature of its continuous delivery with just one or two placements per year."
The phase 2 study enrolled 155 type 2 diabetes patients (51-53 patients/arm) across 50 centers in the United States on a stable treatment regimen of metformin. The study compared six different regimens to find the optimal dose range and regimen to take into phase 3:
- ITCA 650 20 mcg/day for 24 weeks
- ITCA 650 40 mcg/day for 24 weeks
- ITCA 650 20 mcg/day for weeks 1 -12 followed by ITCA 650 60 mcg/day for weeks 13 -24
- ITCA 650 40 mcg/day for weeks 1 -12 followed by ITCA 650 80 mcg/day for weeks 13 -24
- Exenatide injection for weeks 1 -12 followed by ITCA 650 40 mcg/day for weeks 13 -24
- Exenatide injection for weeks 1 -12 followed by ITCA 650 60 mcg/day for weeks 13 -24
Summary of week 12 results
Treatment with ITCA 650 at doses of 20 mcg/day and 40 mcg/day resulted in significant reductions in HbA1c at week 12. Initiating treatment with ITCA 650 20 mcg/day resulted in less frequent and less persistent nausea compared with ITCA 650 40 mcg/day and exenatide injection. Nausea rates among patients receiving ITCA 650 at 40 mcg/day were similar to those receiving twice-daily injection of exenatide at 10 mcg BID.
The phase 2 study also incorporated a quality of life (QOL) assessment (DM-SAT) completed by each patient prior to initiating treatment, at treatment week 8 and again at treatment week 20. The results of week 8 assessment suggest that patients receiving either dose of ITCA 650 experienced significantly greater improvement in their quality of life compared to patients receiving twice-daily injections of exenatide.
Summary of week 12 results
"ITCA 650 therapy represents an important advance in the treatment of type 2 diabetes. For the first time, patients are able to receive all the benefits of a GLP-1 therapy without the need for self-injection," said Robert Henry, M.D., Chief, Section of Diabetes, Endocrinology and Metabolism at the University of California, San Diego. He noted, "Injection has been a significant hurdle for the use of GLP-1 therapies for many patients. ITCA 650 allows far more patients to benefit from GLP-1 therapy due to better tolerability and ease of administration. We are highly encouraged by improved levels of patient acceptance of ITCA 650, indicating broader use potential."
Summary of Week 24 Results
After initial treatment week 12, patients on the ITCA 650 arms were re-randomized on a 1:1 basis to either continue on the same dose (20 mcg/day or 40 mcg/day) or escalate to higher doses of ITCA 650 (60 mcg/day or 80 mcg/day) for weeks 13 - 24. Patients on the exenatide injection arm were switched to receive ITCA 650 at a dose of either 40 mcg/day or 60 mcg/day for weeks 13 – 24.
Incremental reductions in HbA1c and weight were observed across all treatment arms at week 24 compared to week 12. Both incremental and aggregate reductions in HbA1c were greatest in the 60 mcg/day and 80 mcg/day dose arms but not measurably different between the two dose arms. Results of the week 20 quality of life assessment suggest that quality of life improved substantially for patients switching from exenatide injection to ITCA 650 and that the substantial improvement observed among patients initially randomized to ITCA 650 was maintained after transition to higher doses of ITCA 650.
"The reductions in HbA1c and weight are substantial, especially for a group of patients on metformin-only background therapy with baseline HbA1c levels at 8.0 percent. We look forward to evaluating optimized dose regimens of ITCA 650 in broader patient populations in the phase 3 program," Graves said.
ITCA 650 therapy in the phase 2 trial was administered for the 90-day treatment period with a single insertion of ITCA 650 on day 1 and removal on or around day 90. The extension phase of the 2 trial evaluated higher doses of ITCA 650 using a single device to deliver 3 months of treatment. The phase 3 study planned for early 2011 will evaluate treatment regimens involving initial 12-week ITCA 650 dosing at 20 mcg/day transitioning to 60 mcg/day thereafter using even longer duration ITCA 650 devices.
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