Washington Editor

Ocera Therapeutics Inc. has moved its first and only compound, AST-120, into pivotal development in patients with fistulizing Crohn's disease.

An initial Phase III study is taking place in North America and Europe, recruiting 240 patients who are being randomized to receive treatment or placebo. Its primary endpoint is testing AST-120's ability to cut the number of draining fistulas in half after four weeks and eight weeks of treatment.

"We're adding centers as we speak," said Xavier Frapaise, the San Diego company's chief medical officer, though he acknowledged that enrollment has started somewhat slowly because of restrictions on patients who have taken Remicade (infliximab, Centocor Inc.) in the past six months. But Ocera is targeting territories with low Remicade usage to add recruits more quickly.

AST-120, an oral therapy that has been used in Japan for 15 years to treat patients with chronic renal failure, is being repositioned by Ocera, which envisions multiple uses for the adsorbent compound. Draining fistulas are found in 20 percent to 40 percent of Crohn's patients, who number more than 500,000 in the U.S.

AST-120's adsorbent nature means that it attracts liquids, gases or suspended matter to adhere to its surface. In the case of Crohn's patients, its underlying properties draw "a lot of the products that play a role in the inflammation of the gastrointestinal tract," Frapaise said.

AST-120 is made of carbon microspheres that contain nanopores and is delivered in 2-g sachets. "These microspheres are not absorbed," he added, noting an inherent safety advantage in such a property. "They stay in the gut."

Frapaise also noted AST-120's advantage over Remicade and other biologics that inhibit tumor necrosis factor (TNF) alpha. Conceding that such products exhibit "a clear activity on Crohn's disease and fistulas," he said "there are many challenges" with them. Their principal drawbacks include cost and safety, the latter resulting from their immunosuppressive properties.

In contrast, Frapaise called AST-120's safety profile "absolutely perfect." A second Phase III study will follow the first, which is expected to complete enrollment in the middle of next year. Secondary endpoints include measures of the product's effect on non-draining fistulas, absolute numbers of draining fistulas, changes in Crohn's Disease Activity Index and Pouchitis Disease Activity Index scores from baseline, the time to relapse from success at eight weeks, the average frequency of liquid bowel movements during the first eight weeks, changes in CRP levels from baseline, treatment failure due to drug therapy switches and safety.

Privately held Ocera acquired AST-120's North American and European rights last year from Tokyo-based Kureha Corp. It has been used in 200,000 patients to date for treating chronic renal failure.

In Japan, the product's use in Crohn's disease has been investigated for a number of years, and the latest data in that space were unveiled at this week's Digestive Disease Week conference in Los Angeles.

Those findings demonstrated a significant reduction in the number of draining fistulas in patients receiving AST-120 compared to placebo.

Ocera, which envisions additional indications for AST-120 such as liver insufficiency and irritable bowel syndrome, as well as chronic renal failure, launched its operations last year with a $14.5 million Series A financing round. In terms of the product's eventual commercialization, "all options are open," Frapaise said.

The biopharmaceutical firm's short-term goal is to in-license additional compounds with proven efficacy and safety profiles in order to build a late-stage clinical pipeline of compounds for gastrointestinal and liver diseases.