NEW YORK (GenomeWeb) – As part of an upcoming phase III study of its investigational non-alcoholic steatohepatitis (NASH) drug elafibranor, French biopharmaceutical firm Genfit is aiming to validate a diagnostic method that uses blood-based biomarkers to identify patients with the disease who are candidates for treatment.
While the test won't be used to select trial participants, it is expected to launch at the same time as elafibranor and help clinicians know which patients should receive therapy without the need for liver biopsy.
NASH is a condition that resembles alcoholic liver disease, but occurs in people who drink little or no alcohol. It is characterized by the accumulation of fat in the liver, along with inflammation and fibrosis. There is no treatment for the condition and it can progress to cirrhosis.
Given NASH's unmet medical need, a number of companies have been moving forward with drug candidates for the condition including Genfit, whose elafibranor recently completed a phase IIb trial and is poised to enter phase III testing in the US and Europe before the end of this year.
Identifying NASH patients, however, is not entirely straightforward. The disease is often asymptomatic in its first stages and is typically suspected when a patient presents with elevated liver enzymes. Currently, diagnosis is only possible through a histological examination of a liver biopsy.
As such, Genfit has been working to develop a companion diagnostic for elafibranor designed not only to identify patients with the disease, but those who are eligible for therapeutic intervention, COO and CSO Dean Hum told GenomeWeb this week.
According to Hum, the US Food and Drug Administration has suggested that potential treatments for NASH should focus on those with moderate-to-severe disease accompanied by significant liver fibrosis. "From a clinical standpoint … the important issue is [being] able to identify the patient who should be treated," Hum said.
To that end, Genfit structured the phase IIb trial of elafibranor to not only evaluate the drug's efficacy but to gather data around biomarkers that can differentiate different stages of NASH.
In that trial, liver biopsies were taken at the beginning of the study to confirm NASH and at the end to evaluate elafibranor's impact. Blood samples were also taken from the study's roughly 300 participants every two months.
Using the blood samples as a starting point, Genfit used two independent bioinformatics approaches to simulate thousands of additional cohorts designed to mimic real-life disease variability and generate diagnostic algorithms. Hum noted that both approaches identified the same five biomarkers — two miRNAs and three known markers of liver damage.
He declined to comment on the biomarkers in detail for competitive reasons, but noted that the algorithms proved more effective than existing scoring systems in identifying patients who are candidates for treatment.
The company is now planning to validate the algorithms in the upcoming phase III study of elafibranor and select the best one for use in a diagnostic kit that is expected to be commercialized around the same time as the drug could hit the market in 2019 or 2020, Hum said. He added that the upcoming trial is expected to enroll about 1,500 patients.
Genfit does not, however, anticipate developing a final diagnostic on its own.
Sample analysis and bioinformatics is "something we do very well," Hum said. "When it comes to developing a diagnostic kit, there are groups … that are much better than we are." Therefore, the company anticipates partnering with another firm on the diagnostic's design and distribution.