Intarcia Therapeutics, Inc. Announces Presentation of Analysis Used for Dose Selection for Global ITCA 650 Phase 3 Program for Type 2 Diabetes at EASD

HAYWARD, Calif., Oct. 3, 2012 /PRNewswire/ -- Intarcia Therapeutics, Inc. announced the presentation of an analysis of phase 2 clinical study results for ITCA 650 (continuous subcutaneous delivery of exenatide) for the treatment of type 2 diabetes at the 48th Annual Meeting of the European Association for the Study of Diabetes (EASD) in Berlin Germany on Wednesday, October 3, by Dr. Robert R. Henry, MD, Chief, Section of Diabetes, Endocrinology and Metabolism at the University of California, San Diego. The analysis was performed to facilitate selection of the optimal dosing regimen to be evaluated in the ITCA 650 global phase 3 clinical program beginning in January 2013.

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"Published data with GLP-1 receptor agonist therapy demonstrate the profound importance of selecting the right dose. This can be complicated when administering a GLP-1 with injections due to variability in drug levels and poor patient adherence to prescribed regimens of regular self-injection," said Robert R. Henry, MD. "ITCA 650's unique ability to consistently deliver a very precise dose of exenatide for up to a full year with just one mini-pump represents a very significant advance in the treatment of type 2 diabetes."

The ITCA 650 phase 2 study enrolled 155 patients whose type 2 diabetes was inadequately controlled with metformin therapy alone. The trial was conducted in two stages:

Selecting an Optimal ITCA 650 Starting Dose
Stage I, weeks 1 - 12, compared two doses of ITCA 650, 20 mcg/day vs. 40 mcg/day, to determine the best starting dose to be administered during the first three months of treatment. In addition, a control arm in which patients were administered exenatide BID injections according to the product labeling was included as a benchmark for both efficacy and tolerability. Both ITCA 650 doses produced a robust 1.0% mean reduction in HbA1c at week 12 compared to a 0.7% reduction in HbA1c in patients receiving exenatide BID injection. The results for exenatide BID injection were consistent with previously published results in patients on metformin monotherapy.

The assessment of patient tolerability over the 12-week initial treatment period revealed a lower incidence of nausea over time and a shorter duration of nausea with the 20 mcg/day dose of ITCA 650 compared with exenatide BID injections. By week 12, only 2% of patients receiving the 20 mcg/day dose of ITCA 650 reported any nausea, while approximately 20% of patients receiving either exenatide BID injection or the 40 mcg/day dose of ITCA 650 reported nausea. Finally, in self-assessments of treatment satisfaction, patients receiving ITCA 650 (20 mcg/day or 40 mcg/day) reported greater improvement in overall quality of life scores than did patients on exenatide BID injections. Based on the results of this multi-factorial assessment, an ITCA 650 dose of 20 mcg/day was selected for further evaluation in phase 3 studies as the best tolerated starting dose that also provided robust HbA1c reductions and enhanced patient-reported quality of life.

Selecting an Optimal Maintenance Dose of ITCA 650
Stage II, weeks 13 - 24, assessed the changes in HbA1c and weight at week 24. Study patients were re-randomized to either remain on their original assigned starting dose of ITCA 650, or to escalate to a higher dose of ITCA 650. Patients who received exenatide BID injections in Stage I were switched to ITCA 650. At week 24, patients whose ITCA 650 dose was increased to 60 or 80 mcg/day achieved greater reductions in HbA1c than did patients who remained on 20 or 40 mcg/day doses of ITCA 650.

Intent to treat population

An additional analysis of week 24 response by baseline HbA1c revealed that patients receiving 60 mcg/day of ITCA 650 who had higher baseline HbA1c achieved greater reductions in HbA1c and were more likely to achieve target HbA1c goals of 7.0% and 6.5% compared with patients receiving lower doses of ITCA 650. Forty-four percent of patients with baseline HbA1c >8.0% achieved the target HbA1c goal of 6.5% by week 24.

Intent to treat population

Daily doses of 40, 60 and 80 mcg/day resulted in similar reductions in mean body weight (7 - 8 lbs) at week 24 compared with baseline. Overall, the ITCA 650 60 mcg/day dose produced robust reductions in HbA1c and appeared to be better tolerated than the 80 mcg/day dose. No patients discontinued treatment for any reason after dose escalation from 20 mcg/day up to 60 mcg/day.

Improvements in patient reported quality of life in patients receiving ITCA 650 in Stage I were maintained or increased during Stage II of the study. The greatest improvements in quality of life were reported among patients who switched from exenatide BID injections to ITCA 650. Based on these findings, 60 mcg/day was selected as the chronic dose for further evaluation in ITCA 650 phase 3 studies.

"We have a high level of confidence that this analysis provides clear direction on the optimal dose regimen as we move ITCA 650 into global phase 3 registration studies," said Michelle Baron, MD, Intarcia's Chief Medical Officer. "We look forward to fully characterizing the clinical profile of ITCA 650. As the first injection-free GLP-1r agonist therapy, ITCA 650 holds the potential to help patients achieve 100% adherence to treatment. This should translate into more durable effects on HbA1c and weight with improved tolerability."

After the completion of the 24-week study, patients were offered the option to participate in an additional 24-week extension to evaluate longer term safety and durability of response. Patients continued to receive the dose of ITCA 650 that they received during Stage II. Eighty-five percent of the eligible patients entered the extension. The robust reductions in HbA1c and weight observed in the 24-week study were maintained throughout the additional 24-week extension with very favorable tolerability.

The global phase 3 program planned for 2013 will evaluate treatment regimens with an initial dose of 20 mcg/day ITCA 650 for three months followed by a chronic dose of 60 mcg/day dose using 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/

About ITCA 650
ITCA 650 therapy for type 2 diabetes involves the continuous subcutaneous delivery of exenatide from a matchstick-size, miniature osmotic pump that is placed subcutaneously to provide continuous and consistent drug therapy. Intarcia's proprietary formulation technology maintains the stability of therapeutic proteins and peptides at human body temperature for extended periods of time.

ITCA 650 can deliver up to a full year of therapy from a single placement. Unlike other extended delivery technologies, such as polymers or albumin fusions, ITCA 650 allows for steady state drug delivery within 24 - 48 hours of placement as well as near immediate withdrawal of therapy, if required, after its removal. 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 and once-weekly self-injection therapy for type 2 diabetes.

About Type 2 Diabetes
The International Diabetes Federation (IDF) estimates that 366 million people have diabetes, approximately 90% of whom have type 2 diabetes, and the number is expected to rise to 552 million by 2030. Approximately half of those affected do not even realize they have diabetes. 4.6 million deaths were attributed to diabetes in 2011 and diabetes is estimated to have resulted in $465 billion, or 11% of total healthcare expenditures in 2011.

About Intarcia
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 human body temperature and to deliver them in a constant and consistent manner via Intarcia's proprietary 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.

SOURCE Intarcia Therapeutics, Inc.