New medicine for rare, chronic liver disease
Ocaliva recommended for conditional approval
The European Medicines Agency (EMA) has recommended granting a conditional marketing authorisation in the European Union (EU) to Ocaliva (obeticholic acid) for the treatment of patients with primary biliary cholangitis (also known as primary biliary cirrhosis). Ocaliva is to be used in combination with another medicine, ursodeoxycholic acid (UDCA), in patients who have not responded adequately to UDCA, or on its own in adults who are unable to tolerate treatment with UDCA.
Primary biliary cholangitis is a rare and life-threatening disease that causes the gradual destruction of the small bile ducts in the liver. These ducts transport fluid called bile from the liver towards the intestines where it is used to help digest fats. As a result of the destruction of the ducts, bile builds up in the liver causing damage. As the disease progresses, it leads to liver cirrhosis (scarring of the liver) and liver failure, and may increase the risk of liver cancer.
There are limited treatments available for patients with primary biliary cholangitis. Liver transplantation can significantly improve a patient's chance of survival; however this is a long and complex operation only suitable for patients who have advanced liver disease. UDCA is the only medicine currently approved to treat primary biliary cholangitis, but up to half of all patients treated with UDCA either fail to respond to the medicine or experience limited benefits. There is therefore a clear unmet medical need for these patients, as well as for patients who are unable to tolerate treatment with UDCA.
Obeticholic acid is a semi-synthetic bile acid that works by activating the farnesoid X receptor (FXR), which controls the production of bile. By activating this receptor, Ocaliva is expected to reduce the production of bile in the liver, thus reducing the exposure of the liver to toxic levels of bile acids.
EMA's Committee for Medicinal Products for Human Use (CHMP) recommended granting a conditional marketing authorisation for Ocaliva. Conditional approval is one of EMA's main mechanisms to facilitate earlier access by patients to medicines that fulfil unmet medical needs. It allows the Agency to recommend a medicine for marketing authorisation before the availability of confirmatory clinical trial data, if the benefits of making this medicine available to patients immediately outweigh the risks inherent in the lack of comprehensive data.
The safety and efficacy of Ocaliva were demonstrated in a phase III study with 216 participants. After 12 months, the proportion of patients achieving reductions in levels of their alkaline phosphatase (an indicator of disease progression) was higher in patients treated with Ocaliva (about 47% compared to 10% in the placebo group).
The most common side effects observed with Ocaliva were itching of the skin (pruritus) and fatigue.
As part of the conditional marketing authorisation, the applicant for Ocaliva has to provide results from two studies. Until availability of full data, the CHMP will review the benefits and risks of Ocaliva annually to determine whether the conditional marketing authorisation can be maintained.
Because primary biliary cholangitis is rare, Ocaliva received an orphan designation from EMA's Committee for Orphan Medicinal Products (COMP) in 2010. Orphan designation is the key instrument available in the EU to encourage the development of medicines for patients with rare diseases. Orphan-designated medicines qualify for ten years' market exclusivity. In addition orphan designation gives medicine developers access to incentives, such as fee reductions for marketing authorisation applications and for scientific advice.
The opinion adopted by the CHMP at its October 2016 meeting is an intermediary step on Ocaliva's path to patient access. The CHMP opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorisation. Once a marketing authorisation has been granted, a decision on price and reimbursement will then take place at the level of each Member State considering the potential role/use of the medicine in the context of the national health system of that country.