Could small molecule medicine treat a rare liver disease?

Positive data was revealed from the pivot ELATIVE^® Phase III trial of elafibranor, an investigational PPAR α,δ dual agonist for primary biliary cholangitis (PBC). The data showed that 51% of patients receiving 80mg of elafibranor, a small molecule treatment, achieved a cholestasis response, compared to 4% on placebo.

The phase III trial recruited 161 patients. It evaluated the novel once-daily peroxisome-activated receptor (PPAR) alpha/delta (α,δ) agonist in patients who previously showed an inadequate response or intolerance to the current standard treatment, ursodeoxycholic acid ( UDCA).

The response of cholestasis to small molecule therapy has been defined in the clinical test such as alkaline phosphatase (ALP) <1.67 x upper limit of normal (ULN), decrease in ALP ≥ 15% and total bilirubin (TB) ≤ ULN at 52 weeks. ALP and bilirubin are important predictors of disease progression. Reductions in levels of both may indicate reduced cholestatic damage and better liver function.

“These are encouraging results which suggest that elafibranor may be an effective treatment to prevent the progression of PBC in patients who have received UDCA. It has a good safety profile and was well tolerated, and may constitute an important new therapeutic option for the long-term treatment of patients with this debilitating disease,” said Howard Mayer, Executive Vice President and Head of Research and Development at Ipsen.

“We welcome these results because PBC remains a disease for which significant unmet medical needs exist,” said Pascal Prigent, CEO of GENFIT.

A significant proportion of patients with PBC cannot benefit from existing therapies. It is estimated that 22.27 out of 100,000 European patients have the rare autoimmune cholestatic liver disease. The disease causes the progressive destruction of the bile ducts in the liver. This damage can inhibit the liver’s ability to move toxins through the body. Scarring of the liver tissue (cirrhosis) can then occur, according to research highlighted by GENFIT and Ipsen.

Positively, regarding the drug developmentMayer added that Ipsen plans to “move forward with regulatory submissions to the US Food and Drug Administration and European Medicines Agency [EMA].”

Full data from the ELATIVE trial for small molecule therapy will be presented at an upcoming scientific meeting.