Company Pursuing Orphan Path to Development in Alagille Syndrome, Progressive Familial Intrahepatic Cholestasis, Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis
SAN DIEGO – September 26, 2013 – Lumena Pharmaceuticals, a company developing oral therapeutics for rare liver diseases, today announced that it has been granted Orphan Drug Designation by the U.S. Food & Drug Administration (FDA) Office of Orphan Product Development for LUM001, the company’s lead drug candidate. LUM001 received Orphan Designation in four rare cholestatic liver diseases including Alagille syndrome (ALGS); progressive familial intrahepatic cholestasis (PFIC); primary biliary cirrhosis (PBC); and primary sclerosing cholangitis (PSC).
Cholestatic liver diseases, such as ALGS, PFIC, PBC and PSC, result in impaired bile acid flow and retention of bile acids in the liver, leading to progressive liver damage that can cause liver failure. By reducing serum bile acids with a once-daily oral drug, LUM001 may offer a novel therapeutic approach to reducing elevated bile-acid levels, preventing liver damage and alleviating severe itching, which is generally the most debilitating symptom afflicting patients with these diseases.
“Orphan Drug Designation from the FDA allows us to pursue an accelerated pathway for development of LUM001 so we can deliver new drug treatments for the patients in desperate need,” said Alejandro Dorenbaum, M.D., chief medical officer of Lumena. “Current therapeutic options for cholestatic liver diseases are of limited efficacy, and surgical approaches to reducing bile acid levels to manage disease symptoms can be disfiguring and prone to complications. The only remaining option for many patients is liver transplant.”
LUM001 has been studied in more than 1,400 patients in 12 different clinical studies. The company also announced today in a separate announcement the initiation of a Phase II study of LUM001 in children with ALGS. The company will also soon be initiating a Phase II study in adult patients with PBC. Later this year, Lumena plans to initiate a Phase II study of LUM001 in pediatric patients with PFIC, and a Phase II study in adults with PSC.
Under the Orphan Drug Act, the U.S. FDA may grant Orphan Drug Designation to a drug intended to treat rare diseases, generally those which affect fewer than 200,000 individuals in the country. Lumena is also pursuing Orphan Drug Designation for LUM001 in all four indications with the European Medicines Agency.
About Alagille Syndrome
ALGS is a rare genetic disorder that can affect the liver, heart, and other parts of the body. Approximately one in every 70,000 children is born with ALGS. In patients with ALGS the bile ducts are abnormally narrow, malformed and reduced in number. This prevents normal bile flow from the liver into the small intestine. As a result, bile builds up in the liver, causing damage that prevents the liver from working properly. ALGS is characterized by elevated bile acids and severe itching, which is generally the most debilitating symptom afflicting children with this liver disease. Treatment with anti-pruritics (anti-itching drugs) 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.
About Progressive Familial Intrahepatic Cholestasis
PFIC is a rare genetic disorder that causes progressive liver disease, which typically leads to liver failure. PFIC is inherited in an autosomal recessive way, meaning that there are mutations in both copies of the gene in order for the disease to be present. The disease is estimated to affect one in every 50,000 to 100,000 people worldwide. In people with PFIC, liver cells are less able to secrete bile due to mutations in proteins that control bile homeostasis. The resulting build up of bile in liver cells causes severe liver disease in affected individuals. Three types of PFIC have been identified.
About Primary Biliary Cirrhosis
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.
About Primary Sclerosing Cholangitis
PSC is a disease that causes chronic inflammation and subsequent scarring of the bile ducts both inside and outside the liver. The blockage of the bile ducts prevents bile from being transported to the small intestines and gall bladder. The accumulation of bile in the liver leads to progressive liver damage, and eventually, liver failure. PSC affects approximately one in 10,000 people, and for reasons that are unknown, it impacts men twice as often as women. Liver transplant is the only known cure for PSC, but transplant is typically reserved for patients with severe liver damage.
LUM001 is an inhibitor of the apical sodium-dependent bile acid transporter (ASBT), which recycles intestinal bile acids back into the circulation. LUM001 has been studied in 12 clinical trials in more than 1,400 subjects. In previous trials, LUM001 was shown to be generally safe, and 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 alleviate symptoms and improve liver function in many patients with cholestatic liver disease.