Data shows promise for injection-free diabetes treatment
Intarcia Presents Positive ITCA 650 Phase 2 Study Results for Type 2 Diabetes at EASD
— First injection-free continuous delivery of GLP-1 therapy demonstrated
substantial HbA1c reductions and weight loss, and improved quality of life—
— Intarcia working with health authorities and preparing for phase 3 in early 2011 —
HAYWARD, Calif., September 22, 2010 – 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
Treatment Arms Weeks 1 – 12 ITCA 650 20 mcg/d ITCA 650 40 mcg/d Exenatide Injection Mean baseline HbA1c (%) 7.90 8.00 8.01 Mean week 12 HbA1c (%) 6.94 6.96 7.19 Mean change -0.96* -1.04* -0.82* Nausea rates week 1 25% 37% 23% week 6 8% 23% 19% week 12 2% 19% 19% Mean improvement in patient-reported QOL week 8 vs. baseline 21% 34% 13% * p<0.001 relative to baseline
“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.
ITCA 650 Dose weeks 13 – 24 20 mcg/day 40 mcg/day 60 mcg/day 80 mcg/day Mean baseline HbA1c (%) 7.96 7.79 8.05 8.03 Mean week 24 HbA1c (%) 7.07 6.93 6.67 6.67 Mean HbA1c change at week 24 -0.89 -0.86 -1.38 -1.36 HbA1c < 7% at week 24 60% 71% 73% 79% Mean weight change at week 24 (lbs) -1.8 -7.9 -6.8 -7.7
“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.
A downloadable version of the ITCA 650 phase 2 presentation from EASD is available on the Intarcia corporate website at: http://www.intarcia.com/media_presentations.html
About ITCA 650
ITCA 650 therapy for type 2 diabetes consists of DUROS continuous subcutaneous delivery of exenatide. The DUROS delivery technology comprises the DUROS device, a matchstick-size, miniature osmotic pump that is inserted subcutaneously to provide continuous and consistent drug therapy. Intarcia’s proprietary formulation technology that maintains stability of therapeutic proteins and peptides at human body temperature for extended periods of time.
The DUROS technology can deliver up to a full year of therapy from a single ITCA 650 insertion. Unlike other extended delivery technologies, such as polymers or albumin fusions, DUROS delivery allows for steady state drug delivery upon insertion and near immediate withdrawal of therapy, if required. ITCA 650 is an investigational new drug and is not currently approved by any regulatory authority. Exenatide, the active agent in ITCA 650, has been approved in the U.S., Europe and many other markets and is currently marketed as a twice-daily self-injection therapy for type 2 diabetes.
About Type 2 Diabetes
According to the National Institutes of Health (NIH), “Approximately 23.6 million Americans have type 2 diabetes, which represents 7.8 percent of the U.S. population and about 1/4 of them don’t even know it. In addition, we now know that at least another 57 million Americans have ‘pre-diabetes.’” Diabetes is
conservatively estimated to be the seventh leading cause of death in the U.S. Minority populations are disproportionately affected, particularly African Americans and Hispanics. For example, African Americans are 1.8 times more likely to develop type 2 diabetes compared to non-Hispanic whites.
According to the Centers for Disease Control and Prevention (CDC), the rate of new cases of type 2 diabetes has nearly doubled in the U.S. in the last decade with these new cases mirroring an increase in obesity rates - a leading cause of type 2 diabetes.
Intarcia Therapeutics, Inc. is a biopharmaceutical company developing therapies to ensure enhanced treatment outcome by optimizing patient adherence and improving the efficacy, convenience and tolerability of drug therapies. Intarcia's drug development expertise and competitive edge are demonstrated by its abilities to stabilize proteins and peptides at above body temperature and to deliver them in a constant and consistent manner via the proprietary DUROS drug delivery platform. Intarcia is pursuing a clinical stage development program for type 2 diabetes and has other programs for weight regulation to control obesity.
Intarcia and its logo are registered trademarks of Intarcia Therapeutics, Inc. DUROS is a registered trademark of ALZA Corporation licensed to Intarcia Therapeutics, Inc. in certain fields.
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_______________________ Victoria Christian Vice President,
Posted: September 2010