Intarcia Announces Presentations At ADA Of Two Successful FREEDOM Phase 3 Trials For ITCA 650 -- A GLP-1 RA For Type 2 Diabetes

BOSTON, June 8, 2015 /PRNewswire/ -- Intarcia Therapeutics, Inc. today announced the presentation of  results from its first two phase 3 clinical trials (FREEDOM-1 and FREEDOM-1 HBL) of its late-stage investigational candidate ITCA 650 (exenatide delivered continuously via a small matchstick-size subcutaneous osmotic mini-pump just once or twice yearly) at the 75^th Scientific Sessions of the American Diabetes Association. Results showing positive data on key endpoints from the trials were highlighted in an oral presentation today and a poster session at the conference in Boston.

Oral Presentation of FREEDOM-1 Results
Oral Presentation of FREEDOM-1: "Clinical Impact of ITCA 650 in Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled 39 Week Trial," led by Julio Rosenstock, M.D., Director of the Dallas Diabetes and Endocrine Center at Medical City and a Clinical Professor of Medicine at the University of Texas Southwestern Medical Center at Dallas.

• FREEDOM-1, a placebo-controlled study, demonstrated positive results for ITCA 650 when added to diet and exercise with or without standard oral diabetes medications, for those patients who were not at goal. All key endpoints were met, including significant reductions in HbA1c and weight, and the percentage of patients treated to goal.
• ITCA 650 produced significant and sustained mean reductions in HbA1c of 1.4% at 39 weeks of treatment (mITT population).
• Two pre-specified patient populations were assessed to determine how HbA1c reductions may vary based on whether or not patients were on a background regimen including a sulfonylurea (SU)-based regimen, or a metformin or diet & exercise regimen without any SUs.
  • Non SU-containing Regimens: Patients primarily on background metformin (~40% of patients), or diet and exercise (~11% of patients), showed a mean HbA1c reduction of 1.7%. 
  • SU-containing Regimens: Those on an SU-based background regimen (47% of patients) had a mean HbA1c reduction of 1.2%.

Significant and progressive weight loss that was dose dependent was observed over 39 weeks (mITT population). Patients on the primary phase 3 dosing regimen lost a mean of 4 kg in the 60 mcg/d ITCA 650 dose group vs. 2 kg in the placebo group at Week 39, which was statistically significant.

The overall tolerability profiles, including G.I. events, were very similar between the 40 mcg/d and the higher 60 mcg/d dose groups. There was a low single-digit discontinuation rate for nausea. No new safety findings were identified compared to what is known for the GLP-1 receptor agonist class. Other adverse events associated with the administration site and the procedures to place and remove the ITCA 650 were generally mild and transient. Discontinuations due to procedures and administration site adverse events were also a very low single digit rate across each arm of the 39-week study.

Dr. Rosenstock, lead investigator for FREEDOM-1, commented: "Reaching and sustaining recommended blood glucose levels and weight loss are important but very difficult goals to achieve and maintain for the majority of patients with type 2 diabetes. These positive phase 3 trial results suggest ITCA 650 holds the potential to open up a new treatment approach to address the significant unmet needs for enhancing treatment adherence to help bring more patients into glycemic control in the growing epidemic of type 2 diabetes."

FREEDOM-1 was a placebo-controlled, double-blind, phase 3 clinical trial that tested the efficacy and safety of ITCA 650 in patients whose HbA1c was not controlled on different oral anti-diabetes drugs or diet and exercise alone. The 460 patients enrolled had baseline HbA1c levels between 7.5% and 10.0% and were randomized into three groups in a 1:1:1 ratio, evaluating ITCA 650 40 mcg/d and 60 mcg/d versus placebo.

Efficacy endpoints were statistically significant for both doses versus placebo in the pre-specified analysis presented at the ADA meeting. Efficacy was assessed with an LOCF analysis at week 39 vs. placebo and a separate mITT population analysis by visit was conducted over the 39 weeks in all patients with a post-baseline HbA1c measurement. Additionally, pre-specified subset analyses of the mITT population treated with different background therapies were carried out to see if results varied across different background therapies.

Baseline characteristics were similar in the three groups: mean HbA1c level of 8.5% (uncontrolled), mean body mass index (BMI) measurement of 33.5 kg/m2 (clinically obese), and mean duration since diabetes diagnosis of 9 years. Ninety percent of the patients in the study were uncontrolled despite being treated with up to three oral anti-diabetes medicines. Subjects in the active arms were treated for the first 13 weeks with 3-month devices that delivered an initial exenatide starting dose of 20 mcg/d, and then treated with 6-month ITCA 650 devices at doses of 40 or 60 mcg/d. The primary endpoint was HbA1c reduction over 39 weeks; secondary endpoints included weight loss and percent of patients reaching goal HbA1c levels of <7%.

Poster Session FREEDOM-1 HBL (High Baseline) Trial Showed HbA1c Reduction of 3.4%
Poster Presentation of FREEDOM-1 HBL: On Saturday June 6^th, poster session (1107-P) titled: "Efficacy and Tolerability of 39 Wks of ITCA 650 (Continuous Subcutaneous Exenatide) in Poorly Controlled T2DM with High Baseline A1c (>10%)," led by Robert R. Henry, M.D., Chief, VA Endocrinology & Metabolism, and Professor of Medicine in Residence at UCSD.

The FREEDOM-1 HBL study was an open-label trial that ran concurrently with Intarcia's FREEDOM-1 phase 3 trial and enrolled type 2 diabetes patients who met all eligibility criteria for FREEDOM-1, but whose baseline HbA1c was greater than 10% but less than or equal to 12%. All patients in this study were treated with ITCA 650 20 mcg/d for the first 3 months and with ITCA 650 60 mcg/d for the next 6 months. Pre-study oral anti-diabetic agents were maintained and remained unchanged for the 39 weeks of treatment. The primary endpoint was change in HbA1c. Secondary endpoints included change in weight from baseline and percentage of patients achieving HbA1c levels <7% at week 39.

At baseline, the 60 patients who entered the study had extremely poor glycemic control as indicated by a mean HbA1c level of 10.8%, a mean body mass index measurement of 32.0 kg/m2 (clinically obese) and mean duration since diabetes diagnosis of 9 years. Notably, significant reductions in HbA1c levels were achieved by week 6, a period during which patients were receiving only the initial 20 mcg/d ITCA 650 dose. The change from baseline was sustained over time, with patients achieving a mean reduction in HbA1c of 3.4% at week 39. 22% of patients achieved HbA1c reductions of 4% or greater and 25% of patients achieved an HbA1c level <7% at the LOCF endpoint. Weight reduction was observed but the results were not statistically significant. Investigators believe this is most likely due to the correction of glycosuria as the blood glucose decreased.

"I am very pleased with these phase 3 results. ITCA 650 delivered excellent results for such a high risk and refractory patient population – and all of this without the need for regular self-injections," said Robert Henry, M.D., Chief, VA Endocrinology & Metabolism, and Professor of Medicine in Residence at UCSD. "I think these new data indicate that the ITCA 650 method of delivery may provide an uninterrupted, smooth and continuous dose that delivers powerful reductions in HbA1c without the need for patient action in terms of managing their medication, which we all know can be extremely challenging. With continued success in the remaining phase 3 trials this year, and a corresponding approval by regulatory authorities, the diabetes community, including payers, providers and patients, could have a new therapeutic choice that may fundamentally change the way we treat diabetes. We desperately need new innovations to positively affect the treatment of this devastating and growing epidemic worldwide."

ITCA 650 treatment was well tolerated in these poorly controlled patients with type 2 diabetes. The most common adverse events were consistent with the known effects of exenatide and the GLP-1 receptor agonist class (mainly gastrointestinal). Most were observed early in the course of treatment and improved over time.

Poster Session: Treatment, Adherence and Change in A1C in Type 2 Diabetes with HBL
On Sunday June 7, a separate poster (135-LB), entitled "Treatment, Adherence and Change in A1C in Type 2 Diabetes (T2DM) with high (>10%) HbA1c," included a comparison of real-world outcomes to results from the FREEDOM-1 HBL study. The retrospective study used the Optum/Humedica SmartFile™ database and a sensitivity analysis was conducted to select a group of type 2 diabetes patients comparable to the FREEDOM-1 HBL study population.

At baseline, the 1,248 patients who met study criteria had a mean HbA1c level of 10.8% and a mean body mass index measurement of 35.1 kg/m2. Mean HbA1c declined 1.8% points from index to outcome HbA1c (mean 364 days) in the base real-world sample. A similar reduction (2.0%) was observed in the sensitivity analysis of patients who likely would have met trial inclusion and exclusion criteria for the FREEDOM-1 HBL study. 16.2% of patients had HbA1c <7% at the end of the observation period. A similar reduction (17.5%) was observed in the sensitivity analysis of patients who likely would have met trial inclusion and exclusion criteria

About Intarcia Therapeutics, Inc.
Intarcia Therapeutics, Inc. is an independent, privately held, biopharmaceutical company developing therapies to enhance treatment outcomes by optimizing and improving the efficacy, continuous administration and tolerability of drug therapies. Delivering medicines just once or twice yearly has the potential to ensure improved patient adherence and compliance, which is otherwise difficult to achieve in most chronic diseases. 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 Intarcia's proprietary technology platform. Intarcia is conducting a phase 3 development program for type 2 diabetes that consists of four separate clinical trials, two of which have been completed. Intarcia continues to conduct research and development, utilizing its platform technology, to treat other chronic serious disorders in the field of diabetes, obesity and autoimmune diseases. For more information on Intarcia, please visit www.intarcia.com

About ITCA 650
ITCA 650 is being developed for the treatment of type 2 diabetes, combining Intarcia's proprietary technology platform involving a matchstick-size, miniature osmotic pump that is placed sub-dermally to provide continuous and consistent drug therapy, and the company's proprietary formulation technology, which maintains stability of therapeutic proteins and peptides at human body temperatures for extended periods of time. Exenatide, the active agent in ITCA 650, is a glucagon-like peptide-1 (GLP-1) receptor agonist currently marketed globally as twice-daily and once-weekly self-injection therapies for type 2 diabetes. If approved, ITCA 650 would represent the first injection-free GLP-1 therapy capable of delivering up to a full year of treatment from a single device placement. ITCA 650 is currently in a global phase 3 clinical trial program called FREEDOM.

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