Genfit knew early on that a quick, easy test for nonalcoholic steatohepatitis would be key to the success of NASH drugs—including its own, elafibranor. Although it canned the NASH program last month after a phase 3 flop, the French biotech is plugging away at its blood-based diagnostic, which could hit the market as early as the second half of 2020.
The test, dubbed NIS4, considers four blood-based markers of NASH and uses an algorithm to calculate a score from 0 to 1. If a patient’s score is higher than a certain threshold, it means their disease is likely severe enough to require treatment. Passing that benchmark indicates that a patient has scarring and fatty liver disease activity, which can include liver fat buildup, inflammation and ballooning of liver cells—a sign that cells are deteriorating and on their way to cell death.
“What we’re trying to do is go beyond you do have NASH or you don’t have NASH. What we’re trying to say is, should you be treated, yes or no?” Genfit CEO Pascal Prigent said in a previous interview.
Genfit has been testing how NIS4 performs in various patient populations, including in men and women, people of various ages, and those who have ailments that often come with NASH, including Type 2 diabetes and high blood pressure. Last week, the company published pivotal data for the test, showing it delivered consistent results across different kinds of patients and worked better than other noninvasive tests used to diagnose NASH. The results appear in The Lancet.
“We wanted to peel back the onion and reveal more and more levels of sophistication in terms of how well does the test perform, not just in and of itself but in comparison to what else is out there,” said Suneil Hosmane, Ph.D., head of global diagnostics at Genfit.
“It was our intent to see where the test would break. We want to… provide context for physicians to use the test in the future and where we want to focus our R&D efforts to fix that problem,” he added. “To our surprise, we didn’t break it. So far, we have yet to identify a population in which there is less performance.”
The investigators tested NIS4 in more than 700 patients, nearly 500 of whom had participated in its phase 3 study, finding it effectively identified patients with or without at-risk NASH, or disease severe enough to need treatment. Unlike other tests commonly used to diagnose NASH, such as the Enhanced Liver Fibrosis (ELF) test, it did not perform better in some patient groups than others.
Hosmane chalks that up to NIS4 being developed specifically for NASH: “We built this test to function for this purpose—we didn’t take something off the shelf and tweak it,” he said.
Although doctors are increasingly using noninvasive tests to help them diagnose NASH, including blood-based and imaging-based tests, liver biopsy remains the gold standard for NASH clinical trials. Biopsies involve taking a small piece of liver tissue and then examining it for markers of the disease. The procedure can be invasive and expensive, not to mention subjective—a pathologist’s findings can depend on which part of the liver the sample was taken from and on the pathologist’s own experience.
The investigators concluded that the use of NIS4 in clinical trials and doctors’ offices “has the potential to greatly reduce unnecessary liver biopsies in patients with lower risk of disease progression.”
Moving forward, Genfit wants to make NIS4 even better. That could mean using even less blood than it currently does and exploring other ways the test can be used.
NIS4 is already available for research use through a partnership with diagnostics giant Labcorp. But Genfit has bigger plans for the test: It plans to license the technology to “a major diagnostic partner” en route to potential regulatory nods in the U.S. and European Union.