Intarcia expects to report Phase III data during the second half of 2015 for the remaining two of its four pivotal trials in its program for once-yearly exenatide implant ITCA 650. If all goes well, it plans to head to the FDA next year. This week, the company offered detailed results at the American Diabetes Association (ADA) conference in Boston from June 5-8 for its two Phase III trials that had already reported data in October 2014.
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| ITCA 650--Courtesy of Intarcia |
Patients in the placebo-controlled FREEDOM-1 trial had a mean, uncontrolled HbA1c level of 8.5% and were clinically obese with a mean body mass index (BMI) measurement of 33.5 kg/m2. The 460 patients in the trial had baseline HbA1c level that ranged between 7.5% and 10%. They were randomized to three groups: ITCA 650 low dose of 40 mcg/d dose, ITCA 650 high dose of 60 mcg/d dose and placebo.
ITCA 650 is a matchstick-size miniature osmotic pump that is placed sub-dermally that gradually releases exenatide, which is already marketed as a twice-daily or once-weekly Type 2 diabetes treatment. The 9-month study found that reduction in HbA1c levels varied according to background patient treatment--90% of patients in the study had levels that remained uncontrolled despite being on up to three oral anti-diabetes drugs.
It was most effective in patients on background metformin (about 40% of subjects) or diet and exercise alone (around 11% of subjects), offering a 1.7% mean HbA1c reduction. Patients already on treatment regimens, including sulfonylurea (roughly 47% of subjects), achieved a 1.2% mean reduction. Overall, in the ITCA 650 arms there was a mean HbA1c reduction of 1.4% at 39 weeks.
Patients in the high-dose arm also lost a mean of 4 kg of excess weight, as compared to only 2 kg in the placebo arm at 39 weeks. Both treatment arms reported a low single-digit trial discontinuation rate due to nausea.
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| Dr. Julio Rosenstock |
"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," said lead investigator for FREEDOM-1 Dr. Julio Rosenstock in a statement. He is the 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.
"These positive Phase III 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," he added.
Intarcia also reported detailed data from the FREEDOM-1 HBL study, an open-label trial for patients who met all the criteria for FREEDOM-1 except they had a baseline HbA1c that was greater than 10% but less than or equal to 12%.
The treatment proved to be more effective in this group, offering a mean reduction of 3.4% from an average baseline of 10.8%. For this group, weight reduction was observed but not statistically significant.
"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 Dr. Robert Henry, chief of VA Endocrinology & Metabolism and professor of medicine in residence at University of California at San Diego, in a statement. "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."
Intarcia has raised $300 million this year alone in a synthetic royalty with equity conversion that valued the company at $5.5 billion. The two outstanding Phase III trials slated to report later this year are FREEDOM-2 and FREEDOM-CVS.
The former is expected to have data in August; it is a 12-month, 500-patient study comparing ITCA 650 to Januvia sitagliptin from Merck in achieving glycemic control in patients on metformin alone. The latter is a cardiovascular outcomes study in more than 4,000 patients that's expected to track event-based outcomes over three to five years.
- here is the release