On 01 June 2017, the EMA launched a public consultation to collect feedback on a further reflection paper on the regulatory requirements for drug development to treat chronic non-infectious liver diseases. There is currently an unmet medical need for treatments of these diseases which include non-alcoholic steatohepatitis (NASH), primary sclerosing cholangitis (PSC) and primary billiary cholangitis (PBC). At present, there are a few drug development programmes to treat these conditions, however the EMA has stated that “current regulator experience reveals the need for further guidance” to avoid any potential complications during the drug development process.
All three of the diseases have a long progression and symptoms that are either unspecific or non-predictive of long-term outcomes. Additionally, the EMA says the use of “hard” clinical outcomes like liver transplantation or death raise viability issues for these studies and patients are often deterred from enrolling in studies due to the repeated liver biopsies. Due to these challenges, the EMA is calling for a validated surrogate endpoint to reduce the need for biopsies.
The EMA has also stated that “There is also a need for the identification of the most suitable patient population, balancing unmet medical needs, the mechanism of action of drug candidates, and the disease severity with regard to grade of inflammation and stage of fibrosis development”.
The agency has also indicated that there are questions as to the appropriate requirements for observation, licensing, post-approval studies and addressing ethical questions and patient adherence.
Given all these factors and considerations, the EMA is asking for stakeholders, including drug makers, academia, scientific associations and other regulators for input on potential endpoints, surrogate endpoints, biomarkers and study designs that could help guide sponsors’ development programs in this area.