The European Medicines Agency Committee for Orphan Medicinal Products (COMP) has issued a positive opinion for orphan medicinal product status for the Albireo AB’s lead hepatology candidate, A4250, for the treatment of primary billary cirrhosis (PBC), progressive familial intrahepatic cholestasis (PFIC) and alagille syndrome.
The positive opinion of the COMP has now been forwarded to the EU commission for final approval.
PBC is a slowly progressive autoimmune disease of the liver, primarily affecting women. The average age when symptoms start is around 40–50 years of age.
PBC is characterised by destruction of bile ducts resulting in an increased bile acid concentration in the liver inducing inflammation and cirrhosis. There are more than 100.000 patients with PBC in Europe. Main symptoms are fatigue, severe itching and symptoms of cirrhosis.
There is no cure for PBC. Some therapeutic alternatives may slow disease progression and relieve symptoms but some patients may need liver transplantation.
PFIC is a rare disease (estimated prevalence at birth 1/50.000 corresponding to more than 10.000 patients in the European Union) caused by a genetic defect impairing the transport of bile acids thereby inducing toxic levels of bile acid products in the liver inducing severe symptoms such as itching and scarring of the liver (cirrhosis) early in life.
Although milder forms exist, most patients will develop symptoms in early childhood. Without any treatment, PFIC will lead to cirrhosis by age 10-20 years.
In addition to supportive measures, the most common therapeutic modality is a surgical procedure whereby a portion of the bile production is either diverted to a stoma bag or by intestinal bypass to the large bowel. If the patient does not get better, or if there is evidence of liver cancer, then liver transplantation may be needed.
Alagille syndrome is an inherited disease in which the patient has fewer than the normal number of bile ducts leading to increased concentration of bile acids in the liver which induce damage to the liver cells. The estimated number of patients with Alagille syndrome in the European Union is approximately 10.000-20.000. Jaundice, severe itching and growth problems are caused by the liver failure. Approximately 75% of the children diagnosed with Alagille syndrome live to 20 years of age; deaths most often caused by liver failure or heart complications.
The A4250 designation would allow Albireo ten years of marketing exclusivity in EU member countries after obtaining market authorisation, as well as streamlined regulatory review processes and registration.
“We are very pleased with the EMA´s recognition of our technology with A4250 as an orphan medicinal product for the treatment of these liver diseases in Europe”, said Dr. Hans Graffner, Chief Medical Officer at Albireo.
“This designation is an important milestone in our efforts to provide a treatment for patients with cholestatic liver diseases; a disease entity often leading to severe symptoms, liver transplantation and with reduced survival.
“A4250 is an inhibitor of the bile acid transport mechanism and will decrease the toxic levels of bile acids in the liver cells.”