INTARCIA PLATFORM TECHNOLOGY
Intarcia’s platform technology is known as the DUROS® subcutaneous delivery system. The DUROS system is comprised of a small, matchstick-sized osmotic pump that is inserted subcutaneously (just beneath the skin) to deliver a slow and consistent flow of medication. Each device contains an appropriate volume of drug product to treat a patient for a predetermined extended duration of time. The DUROS device is activated when subcutaneous tissue fluid passes through the device inlet, expanding the osmotic engine. The osmotic engine drives the piston at a constant rate, delivering consistent drug levels through the device outlet. The device can be inserted in a subcutaneous space in various locations on the arms and abdomen during a reimbursable in-office procedure, in as little as five minutes by a physician or physician's assistant, and ensures 100 percent patient adherence to therapy.
Delivering drugs via the DUROS technology avoids unwanted peak drug levels often associated with toxicities and sub-therapeutic troughs often associated with suboptimal therapeutic effects. Another key aspect of the DUROS technology is the unique formulations that maintain stability of proteins and peptides at human body temperature for extended periods of time. This advance in formulations allows continuous delivery of effective therapy with less frequent administration thereby ensuring compliance and improving patient convenience. The DUROS device was first used as a drug delivery technology for the FDA-approved product Viadur® in the delivery of leuprolide acetate.
DUROS Technology: Revolutionizing How Type 2 Diabetes is Treated
Overview
Type 2 diabetes is currently one of the largest public health threats facing the U.S. over the next decade, and existing treatment options fail to address the myriad of complications patients endure including weight gain, suboptimal blood glucose control, nausea, and poor adherence with treatment. Many patients take several doses of oral medications daily and/or must inject themselves daily. Intarcia recognized the potential for the DUROS delivery system to reshape the way diabetes is treated by offering patients and their health care providers with a more convenient long term treatment regiment. The result is the investigational treatment now in late stage development – ITCA 650.
As part of a robust clinical trial program to develop ITCA 650, Intarcia paired the DUROS device with exenatide, a proven safe and effective drug commonly used for type 2 diabetes. ITCA 650 is a matchstick-sized, miniature osmotic pump that is inserted subcutaneously to provide continuous and consistent treatment of exenatide therapy for up to a year. 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.
How the Device Works
Intarcia's clinical stage type 2 diabetes candidate, ITCA 650 involves the delivery of exenatide, an approved incretin mimetic using the DUROS delivery system. The DUROS delivery system is a matchstick-sized device consisting of a cylindrical titanium alloy reservoir. Once inserted under the skin, water from the extracellular fluid enters the device at one end, by diffusing through a semipermeable membrane directly into a salt osmotic engine that expands to drive a piston at a controlled rate of travel. This forces the drug formulation to be released in a slow and consistent fashion through the exit port, or diffusion moderator at the other end of the device.
Phase 2 Trial Results
Study Design and Summary of Week 48 Results
Final 48 week results of the ITCA 650 phase 2 study were presented at the 47th Annual Meeting of the European Association for the Study of Diabetes in September 2011. The phase 2 study enrolled 155 type 2 diabetes patients (51-53 patients/arm) across 50 centers in the United States. Prior to study entry, patients were on a stable treatment regimen of metformin monotherapy that was continued throughout the study. The study compared six different regimens of ITCA 650 to optimize dose and regimen for further evaluation in phase 3 studies.
After an initial 12-week treatment period comparing ITCA 650 20 mcg/day and 40 mcg/day with twice-daily injections of exenatide, patients continued treatment with one of 4 doses of ITCA 650: 20, 40, 60 or 80 mcg/day in the following manner through the planned 24-week endpoint:
| Treatment Weeks 1 – 12 | Treatment Weeks 13 – 24 | |
| ITCA 650 20 mcg/day | → | ITCA 650 20 μg/day |
| ITCA 650 20 mcg/day | → | ITCA 650 60 μg/day |
| ITCA 650 40 mcg/day | → | ITCA 650 40 μg/day |
| ITCA 650 40 mcg/day | → | ITCA 650 80 μg/day |
| Exenatide BID injection | → | ITCA 650 40 μg/day |
| Exenatide BID injection | → | ITCA 650 60 μg/day |
Clinical sites were authorized to offer patients an extension of up to an additional 24 weeks of ITCA 650 treatment to evaluate longer term safety and durability of response. Among the sites participating in the extension phase, a total of 86 patients (85% of patients at these sites) elected to continue ITCA 650 therapy.
Sustained reductions in HbA1c, FPG and weight were observed across all treatment arms from week 24 through week 48. Reductions in HbA1c were greatest in the 60 mcg/day and 80 mcg/day dose arms but not statistically different between these two dose arms.
| ITCA 650 dose weeks 13 – 48 | 20 mcg/day | 40 mcg/day | 60 mcg/day | 80 mcg/day |
| Mean baseline HbA1c (%) | 7.8 | 7.8 | 8.1 | 7.9 |
| Mean week 48 HbA1c (%) | 6.8 | 6.8 | 6.6 | 6.5 |
| Mean HbA1c change at week 48 | -1.0 | -1.0 | -1.5 | -1.4 |
| Mean weight change at week 48 (lbs) | -6 | -10.8 | -7.7 | -7.9 |
Throughout the extended treatment duration of the study, there were no treatment discontinuations due to nausea. Numeric improvements were observed in measures of blood pressure and lipids at weeks 24 and 48 compared to baseline.
Patient Satisfaction with ITCA 650 Therapy
A survey utilizing the Diabetes Medication Satisfaction Tool (DM-SAT), a validated and published self-assessment tool was administered to patients in the ITCA 650 phase 2 study before treatment began, at treatment week 8 and at treatment week 20. Study results indicated that patients receiving ITCA 650 at doses of either 20 mcg/day or 40 mcg/day experienced a statistically significant improvement in their quality of life after 8 weeks of ITCA 650 therapy compared with their level of satisfaction at study entry on oral metformin therapy. Patients on either dose of ITCA 650 also experienced a greater increase in their level of satisfaction with treatment compared with patients on twice-daily self-injections of exenatide. Results of the week 20 assessment showed a statistically significant improvement in treatment satisfaction among patients switching to ITCA 650 from exenatide injection. The substantial improvement observed among patients initially randomized to ITCA 650 was maintained after transition to higher doses of ITCA 650.
Placement and Removal of DUROS Technology
Device Location
The basis for the successful use and removal of ITCA 650 is a simple but carefully performed subcutaneous placement. The placement process is typically a 5-10 minute, painless procedure done in the doctor's office. ITCA 650 is inserted subcutaneously into one of four quadrants of the abdomen in the area extending below the ribs and above the beltline. The device is inserted at a depth of 0.5 centimeters just under the skin, so once fully inserted, the skin is not raised and the device is not visible or felt by the patient.
Device Placement
The physician will first mark the location of the placement site on the patient's abdomen to assist with the correct placement of the ITCA 650. The physician will then clean the placement sight and will use a local aesthetic agent to numb the area. After making a very small incision, and using a surgical placement tool, the physician will place the ITCA 650 at a depth of 0.5 centimeters below the skin. Once inserted, the physician will clean the skin, apply a skin protectant and cover with a sterile adhesive bandage. The patient should then be sure to keep the area clean and dry for 24-hours, and avoid heavy lifting for 48-hours. The incision typically takes 2-3 days to heal.
Device Removal
The physician will first inspect the placement site and identify the location of the ITCA 650. Once the ITCA 650 has been identified, the physician will mark the location with a marking pen to assist with administering a local anesthetic and to assist in making the removal incision. After applying the anesthetic, the physician will then make a small incision at the placement site, to promote expulsion of the ITCA 650.
When the end of ITCA 650 is visible in the incision, the physician will grasp the device and remove it from the patient's abdomen. Once removed, the physician will clean the skin, apply a skin protectant and cover with a sterile adhesive bandage. The patient should then be sure to keep the area clean and dry for 24-hours, and avoid heavy lifting for 48-hours. The incision typically takes 3-4 days to heal and the sterile bandage should remain intact for this time.
