Arrowhead initiates Adipotide Phase 1 trial in obesity

Jul 11 2012

Arrowhead Research Corporation (NASDAQ: ARWR), a targeted therapeutics company, today announced that the first patient has been dosed in a Phase 1 clinical trial with Adipotide®, a new class of treatment for obesity. Adipotide, formerly known as Prohibitin-TP01, is a synthetic peptide that targets a protein on the surface of blood vessels supporting white adipose tissue (fat), disrupting the blood supply to fat cells and causing them to be reabsorbed and metabolized. Treatment has led to substantial weight loss, decreased food intake, and rapid metabolic changes with implications for Type II diabetes in multiple experimental animal models.    

The Phase 1 trial is designed to evaluate a single 28 day cycle of Adipotide in patients with castrate-resistant prostate cancer and no standard treatment options. The study is intended to identify a maximum tolerated dose, assess pharmacokinetics, measure the change in weight, and monitor disease progression, in addition to other secondary outcome measures. Fat tissue is known to produce substances that can promote prostate cancer growth. Investigators at the MD Anderson Cancer Center, who are conducting and bearing the costs of the clinical trial, also seek to learn if decreasing white fat, the type of fat associated with obesity, can slow the growth of prostate cancer.

Patients will receive Adipotide as an injection under the skin once daily for 28 days. Up to five dose levels will be tested with three participants enrolled at each dose level. The first group will receive the lowest dose and each new group will receive a higher dose level than the group before it, based on an evaluation of observed safety. This will continue until the highest dose of Adipotide with acceptable safety is found or all five dosing cohorts have been completed.

"We are delighted to announce that patient dosing has begun in the Phase 1 trial of Adipotide," said Dr. Chris Anzalone, President and Chief Executive Officer of Arrowhead. "Obesity and its related co-morbidities represent a serious public health issue in the United States and other parts of the world. We believe Adipotide is a promising pharmacological option to combat it. Through our unique approach of acting directly on the vasculature of fat rather than the brain, we hope to avoid the many safety concerns that have hindered other anti-obesity drug candidates. Moreover, the preclinical efficacy we have seen is striking and we are eager to see results from this first-in-man study."

Multiple independent studies with Adipotide have demonstrated that obese rodents lose up to 30% of their body weight after only 28 days of treatment while lean animals show no weight loss. Studies have also shown that obese animals undergo rapid improvement in pro-diabetic metabolic markers, including significantly improved insulin sensitivity, improved glucose tolerance, and a reduction in serum triglycerides after only 2-3 days of treatment. Adipotide has been further studied in non-human primates, and it has been reported that after 28 days of treatment obese rhesus monkeys lost an average of 11% of their body weight, experienced a reduction in body mass index and abdominal circumference, and showed marked improvements in insulin resistance, a marker for type II diabetes. These data were published in the peer-reviewed journal Science Translational Medicine in November 2011 (Sci Trans Med 3, 108-112 (2011) DOI: 10.1126/scitraslmed.3002621).