AC-820

A pivotal Phase 3 study is being prepared in the U.S. under a special protocol assessment. AC-820, a small synthetic molecule, is a highly selective κ (kappa)-opioid receptor agonist showing a potent anti-itching activity. The compound is orally administered and has demonstrated a high safety profile in over 1,500 subjects including over 1,100 dialysis patients.

The current primary indication for AC-820 (a.k.a., Nalfurafine HCl or TRK-820) is uremic pruritus, a severe systemic itch that occurs in many kidney dialysis patients. According to the latest published research by DOPPS, or Dialysis Outcome and Practice Patterns Study, 42~45% of dialysis patients routinely suffer from moderate to extreme itching and additional about 30% experience mild itching. This study involved over 38,000 hemodialysis patients in 12 nations including Australia, Belgium, Canada, France, Germany, Italy, Japan, New Zealand, Spain, Sweden, the United Kingdom, and the United States. The severe itching in uremic pruritus patients can have a profound effect on their quality of life, such as sleep. The DOPPS report demonstrated that the sleep disturbance by uremic pruritus is associated with a 17-20% increase in mortality in this population (p<0.0001). Treatment of pruritus in this population is more than just treating an “itch”. There are currently no U.S. Food and Drug Administration-approved therapies to address this condition. Off-label uses of other therapies provide with very limited relief. Increasing the dialysis dose or diligent control of key clinical parameters such as calcium, phosphate, and PTH also do not eliminate this condition. Currently, the only way to cure this problem is through kidney transplantation. According to the United States Renal Data System, or USRDS, there were over 500,000 end stage renal disease patients in the United States in 2006, with approximately 355,000 of these individuals receiving dialysis therapy. The dialysis population is continuously growing by about 4~5% every year.

AC-820 has been evaluated in multiple clinical studies. In the latest pivotal Phase 3 clinical study conducted in Japan, AC-820 demonstrated significant reduction in itching intensity in uremic pruritus patients. In a separate long term study with uremic pruritus patients, AC-820 exhibited high safety profile. The first product approval for this indication was given by the Japanese Regulatory Agency in January 2009 based on these results.

AC-820 is believed to exert its activity by sending an anti-itch signal by acting as a selective agonist for κ-opioid receptor. Therefore, the compound has the potential to reduce itching intensity regardless of its origin. There are many diseases that are known to cause severe and chronic itching conditions such as hepatic cirrhosis, eczema, psoriasis, neurological disorders, endocrinology diseases, as well as cancers and infections. Acologix expects that AC-820 could be useful to treat such other itching conditions and plans to explore its efficacy outside of the renal field. Because of the generally poor understanding of itching mechanisms, development of an anti-itch therapeutic has been challenging. AC-820 represents the first compound developed for this indication.