Intarcia Presents Results From Two Successful Phase 3 Trials For ITCA 650, Its Investigational Therapy In Type 2 Diabetes, At 51st EASD

STOCKHOLM, Sept. 16, 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 matchstick-size subcutaneous osmotic mini-pump) at the 51^st European Association for the Study of Diabetes (EASD) Meeting in Stockholm, Sweden.

"The sweeping clinical success of ITCA 650 in three successive Phase 3 trials, including the two being presented at EASD, makes me optimistic that a totally new therapeutic approach is on the near-term horizon – one capable of delivering very significant progress against major unmet needs in type 2 diabetes around the world," said James R. Gavin III, Clinical Professor of Medicine at Emory University School of Medicine, Clinical Professor of Medicine at Indiana University School of Medicine, and former president of the American Diabetes Association. "I am impressed by the multi-dimensional superiority demonstrated over Januvia® as reported in the latest FREEDOM-2 top-line results. In a real-world setting, one may see the differences in efficacy become even greater in favor of ITCA 650 because real-world compliance and adherence to daily therapy is a major challenge. This deserves further investigation to fully understand real world outcomes. The global diabetes community needs a more efficacious therapy for diabetes, and for many patients that means it has to be a game-changing therapy that can turn medication non-adherence on its head without needing to rely on changing patient behavior."

FREEDOM-1 Results – Oral Presentation
FREEDOM-1 clinical trial results were presented today by Michelle Baron, M.D., FACE, Vice President, Clinical Research and Chief Medical Officer of Intarcia in an oral presentation entitled "A randomized, double-blind, placebo-controlled, 39 week trial of ITCA 650 as add-on therapy in 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 antidiabetic 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.

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. Patients in the study were uncontrolled despite almost ninety percent being treated with up to three oral antidiabetic drugs. 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%.

Highlights from the study include:

• 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 might vary based on whether or not patients were on a background regimen including a sulfonylurea (SU) therapy.
  • Patients primarily on background metformin (~40% of patients), or diet and exercise (~11% of patients), showed a mean HbA1c reduction of 1.7%.
  • Those on an SU-based background regimen (47% of patients) had a mean HbA1c reduction of 1.2%.

Significant and progressive dose-dependent weight loss was observed over 39 weeks (mITT population). Patients 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, a difference that was statistically significant.

Dr. Baron commented: "Our goal as a Company has been to create a disruptive innovation in type 2 diabetes that has the potential to break through current treatment paradigms to achieve better clinical results for patients currently not at target glucose levels. These positive Phase 3 trial results reveal that ITCA 650 has the potential to open up a new treatment approach that holds promise to significantly enhance control and help more patients achieve their glycemic goals and maintain them over time. Based on our exciting results to date, we are planning to initiate additional comparative Phase 3b and 4 trials to build on this evidence and also fully characterize the real-world outcomes and adherence advantages vs. current standard of care medicines."

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.

FREEDOM-1 HBL (High Baseline) Results
Earlier today, Robert Henry, M.D., Chief, VA Endocrinology & Metabolism, and Professor of Medicine in Residence at UCSD presented the FREEDOM-1 HBL results during a poster session entitled "Efficacy and tolerability of ITCA 650 (continuous subcutaneous exenatide) for 39 weeks in patients with poorly controlled T2DM and high baseline HbA1c (>10%)."

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.

Highlights from the study include:

• 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.

Dr. Henry commented on the results: "I am delighted to see such impressive improvements in a high risk and refractory patient population made possible by ITCA 650. I think these new data indicate that the ITCA 650 method of injection-free delivery may provide an uninterrupted, smooth and continuous dose that delivers powerful reductions in HbA1c without the need for patients to manage their medication – which we all know can be extremely challenging. With continued success in the remaining Phase 3 trials this year, and pending an approval by regulatory authorities, the diabetes community, including payers, providers and patients, could have a new therapeutic option that fundamentally changes the way we treat type 2 diabetes. We need new innovations like this if we are ever going to effectively treat the majority of patients who are still unable to achieve glycemic control in this increasingly devastating and growing worldwide epidemic."

Weight reduction was observed in the trial, but the results were not statistically significant. Investigators and experts believe, based on published literature from multiple trials in this distinct population, this is most likely due to the correction of glycosuria, which stopped the loss of calories in the urine that is common among such uncontrolled patients. 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.

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, three 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. Intarcia has partnered with French pharmaceutical company Servier to develop ITCA 650 outside the U.S. and Japan. 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.

About Recent FREEDOM-2 Phase 3 Successful Top-Line Clinical Results vs. Januvia
Intarcia announced in the U.S. on August 18, 2015, the positive top-line results of its 52-week FREEDOM-2 clinical trial to determine the comparative efficacy of the Company's late-stage investigational candidate ITCA 650 to Merck's Januvia^® in reducing HbA1c and body weight (BW) in patients with type 2 diabetes following a year of treatment. The announcement was part of Intarcia's obligation of transparency to key stakeholders involved in the Company's forward success. The full data are being held for publication in a major peer-reviewed journal and presentation at a forthcoming major medical meeting. FREEDOM-2 data are not being presented at EASD in Stockholm. The press release regarding FREEDOM-2 is archived and available on www.intarcia.com in the "Investors & Media" section.

About Poor Control and Poor Adherence as Major Impediments to Progress Against T2D
A "real-world look" at patient compliance and adherence with prescribed medications in type 2 diabetes was presented at the recent American Diabetes Association's 75^th Scientific Sessions in Boston. Poor adherence is a clinical problem intrinsic to oral and injectable medicines, which are the most commonly prescribed methods of administration. Retrospective data showed the majority of patients do not adhere with physician instructions regarding effective dosing of these medications over time. Data presented showed a high correlation between poor adherence with prescribed therapies and poor glycemic control. Sustained poor glycemic control resulted in poor clinical outcomes, which in turn results in significant clinical and economic burden.

"The clinical and economic consequences of poor control and poor adherence in type 2 diabetes are so sizable and predictable that fixing it must become a top priority," said William H. Polonsky, Ph.D., CDE, President, Behavioral Diabetes Institute, and Associate Clinical Professor, UCSD. "Decades of attempts to encourage more effective self-care behaviors, including medication adherence, have generally failed to work adequately, and sustainably, for the vast majority of patients. No medicine is good, better, or best if the patient doesn't take it. A shift in the delivery model to one that can much more easily and more effortlessly deliver consistent and continuous medication, instead of continuing to rely on time-consuming and often frustrating efforts to address the day-to-day behavioral obstacles to taking medication that our patients face, would be well worth a small disruption in how it is administered. We have here an exciting opportunity for helping our patients achieve much greater success with their diabetes management."

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