Company receives first positive opinion in the European Union for Primary Sclerosing Cholangitis
SAN DIEGO – November 18, 2013 – Lumena Pharmaceuticals, a company developing oral therapeutics for rare liver diseases, today announced that it has received positive opinions for four Orphan Drug Designations by the European Medicines Agency (EMA) Committee for Orphan Medicinal Products (COMP) for LUM001. The company’s lead drug candidate, LUM001, received the first positive opinion granted by the EMA for primary sclerosing cholangitis (PSC). In addition, the company received positive opinions for LUM001 in three other rare cholestatic liver diseases including Alagille syndrome (ALGS), progressive familial intrahepatic cholestasis (PFIC), and primary biliary cirrhosis (PBC). This follows the Orphan Drug Designation in September by the U.S. Food & Drug Administration (FDA) Office of Orphan Product Development for LUM001 in the same indications.
“The EMA’s recognition of LUM001 as a potential treatment for the thousands of patients who suffer from these debilitating, rare liver diseases is another important step in our development plans,” said Mike Grey, Lumena’s chief executive officer and president. “We will continue to work diligently to develop LUM001 for the patients in serious need of safe, non-invasive therapeutic options to prevent progressive liver damage and the accompanying devastating symptoms.”
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.
LUM001 has been studied in more than 1,400 patients in 12 different clinical studies. Lumena is currently evaluating LUM001 in a Phase II study in children with ALGS and a Phase II study in adults with PBC. Later this year, Lumena plans to initiate a Phase II study of LUM001 in children with PFIC, and a Phase II study in adults with PSC.
The positive opinion of the COMP has now been forwarded to the EU commission for final approval. The EMA’s Orphan Drug Exclusivity is designed to provide regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or debilitating conditions with a prevalence in the EU of not more than five in 10,000. Orphan medicinal products receive at least 10 years of market exclusivity in the EU after receiving marketing authorization.
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.