Lumena Pharmaceuticals, a company developing oral therapeutics for rare liver diseases, has dosed the first patient in the CLARITY phase II study of its drug candidate LUM001 in patients with primary biliary cirrhosis (PBC).

LUM001 is being developed as a possible therapy for a number of cholestatic liver diseases including, PBC, Alagille syndrome, progressive familial intrahepatic cholestasis and primary sclerosing cholangitis, that result in impaired bile acid flow and retention of bile acids in the liver, leading to progressive liver damage and, ultimately, liver failure.  In the CLARITY Phase II study, LUM001 is being evaluated for its ability to alleviate the symptom of severe itching associated with PBC.

Cholestatic liver diseases are characterized by elevated bile acids and severe itching, which is generally the most debilitating symptom afflicting adults and children with these diseases. Treatment with anti-pruritics typically provides only modest relief. Procedures that remove bile from the circulation can lower serum bile acids, reducing itch and improving liver function in some patients, but tend to be invasive in nature. LUM001 is an inhibitor of the apical sodium-dependent bile acid transporter (ASBT), which recycles intestinal bile acids back into the circulation. By reducing serum bile acids with a once-daily oral tablet, LUM001 may offer a novel therapeutic approach for alleviating the severe itching and progressive liver damage associated with many cholestatic liver diseases.

"There is a critical need for treatment options for the many patients with PBC suffering from severe itching and the associated scratching and sleep disruption they must endure on an ongoing basis," said Marlyn Mayo, Associate Professor, Internal Medicine, University of Texas Southwestern Medical Center and principal investigator of the CLARITY study. "Inhibiting bile acid recirculation to the liver pharmacologically with LUM001 has the potential to relieve symptoms, improve liver function, and dramatically impact patient health."

The CLARITY study is a randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of LUM001 in combination with ursodeoxycholic acid (UDCA) versus UDCA plus placebo in adults with PBC. This international, multi-center study will enroll 60 adult patients experiencing moderate to severe pruritus (itching). The primary endpoint of the study is change from baseline in pruritus compared to placebo. Secondary endpoints include changes from baseline in liver enzymes and other biochemical markers of cholestatic liver disease compared to placebo.

LUM001 has received Orphan Drug Designation by the U.S. Food & Drug Administration (FDA) Office of Orphan Product Development in four rare cholestatic liver diseases including primary biliary cirrhosis; progressive familial intrahepatic cholestasis; Alagille syndrome; and primary sclerosing cholangitis.

LUM001 has been studied in 12 clinical trials in more than 1,400 subjects. In previous trials, LUM001 was shown to be generally well tolerated, the most common side effect, gastrointestinal disturbance, was usually mild and transient in nature. Clinical studies have demonstrated that LUM001 can reduce serum bile acid levels. Reductions in bile acids may be effective in alleviating symptoms and improving liver function in many patients with cholestatic liver disease. The company has also initiated a global clinical program to study LUM001 in children with Alagille syndrome and will initiate Phase II studies in patients with progressive familial intrahepatic cholestasis, and primary sclerosing cholangitis in late 2013.

PBC is thought to be caused by an autoimmune process. The disease affects women more often than men, and is usually diagnosed between the ages of 40 and 60. In this chronic condition the bile ducts in the liver become inflamed and are slowly destroyed. Bile duct damage results in accumulation of bile acids and other harmful substances in the circulation that cause injury to the liver. In patients with PBC the liver disease can progress to irreversible cirrhosis and liver failure.

Lumena Pharmaceuticals is a San Diego-based company developing oral therapeutics for patients with rare and debilitating liver diseases. Lumena's lead candidate, LUM001, has been studied in more than 1,400 patients in 12 different clinical studies and is being evaluated in phase II studies in patients with Alagille syndrome and primary biliary cirrhosis.