SAN FRANCISCO — A clinical phase II/III trial of a potential oral medication for pouchitis will begin this year, following a Food and Drug Administration decision to grant orphan drug status to the experimental compound AST-120.
There are no approved treatments for pouchitis, a problem seen in approximately half of patients who undergo a colectomy and surgical creation of a j-pouch to treat ulcerative colitis. The pouch becomes inflamed and is associated with frequent and severe diarrhea, abdominal cramps, fever, and dehydration.
Pouchitis affects fewer than 100,000 patients in the United States, allowing AST-120 to earn its orphan drug status, which is designed to encourage companies to develop medicines for rare diseases. Orphan drug status grants 7 years of exclusive rights to the market of the drug, among other benefits.
Ocera Therapeutics also is conducting studies of AST-120 for the treatment of Crohn's disease, fistulizing Crohn's disease, and other GI diseases, Dr. Laurent Fischer said at a JP Morgan Healthcare conference. Dr. Fischer is president and CEO of the San Diego-based company, which licensed AST-120 from its Japanese developers.
The first 10 patients with pouchitis in an open-label proof-of-concept trial showed significant improvements after 4 weeks of taking 2-g sachets of AST-120 t.i.d., he said. Nine patients completed therapy and one dropped out because of an upper respiratory tract infection. Four patients had complete remission, and five had a clinical response.
AST-120 is an oral spherical adsorptive carbon that may adsorb bile acids and bacterial toxins associated with pouchitis, potentially protecting the intestinal mucosa of the j-pouch from inflammation. AST-120 does not absorb vitamins and digestive enzymes, and is not itself systemically absorbed in the GI tract.
The drug is marketed in Japan as a treatment to delay the time to dialysis and to decrease uremic symptoms in patients with chronic renal failure. AST-120 has been studied in Japan for the treatment of Crohn's disease in more than 2,600 patients, and appears to have a good safety profile, Dr. Fischer said.
A separate, ongoing phase III study in the United States of AST-120 to treat fistulizing Crohn's disease may produce results in time for presentation at the Digestive Disease Week conference in May, he added.
AST-120 is also being studied for the treatment of Crohn's disease, fistulizing Crohn's disease, and other GI diseases. DR. FISCHER