What the NASH field needs, says Genfit CEO Pascal Prigent, is something like Hb1Ac for diabetes: a test that’s easy to do and that’s “commonly regarded as the right way to monitor the disease that everybody can use.” To that end, Genfit is working on a blood test that could become the first diagnostic approved specifically for nonalcoholic steatohepatitis (NASH).
The test, known as NIS4, considers four blood-based biomarkers of nonalcoholic steatohepatitis (NASH), a form of the so-called fatty liver disease, and uses an algorithm to calculate a score from 0 to 1. If a patient’s score is above a certain threshold, it means that they have an 80% or higher chance of having severe enough disease to require treatment. That threshold is a score of 0.62, which indicates that a patient has a NASH activity score higher than 4 and scarring classified as stage 2 or worse.
“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?” Prigent told FierceBiotech at the annual meeting of the American Association for the Study of Liver Disease.
It’s not a companion diagnostic, Prigent stressed: “It tells you nothing about [our late-stage NASH hopeful] elafibranor. Once you’re told you should be treated, you can be treated with [Intercept’s] OCA, or with us, or whatever.” Elafibranor, a dual agonist of the PPAR-alpha and PPAR-delta, is in phase 3 studies. Genfit hopes it will become one of a batch of new drugs in the coming years to treat the disease, which could be worth tens of billions of dollars a year at peak.
Lots of companies, including Genift, have hit setbacks in NASH studies but are hoping that better understanding of the disease will help tweak out these issues. One of the bigger issues analysts have had with NASH drug is just about testing, so Genfit is hoping to cover its bases here, too.
The current gold standard for NASH diagnosis is liver biopsy, where a small piece of liver tissue is taken and then examined for markers of the disease. This can be painful for patients, and difficult to explain when there are few symptoms for NASH until later on, hence it's description as the "silent disease." Doctors also use a variety of noninvasive tests to help them diagnose NASH, including MRI- and ultrasound-based tests, but Genfit went with a blood-based one because it's relatively inexpensive and doesn’t require a technician to carry it out and a specialist to read the results.
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Getting a test like H1bAc to market would be instrumental in the success of NASH drugs.
“It is something we realized quite early when we started the development of elafibranor—as long as biopsy is the only way to diagnose NASH patients, that market is never going to be a large market because patients are so reluctant to do biopsies,” Prigent said. What’s more, in its conversations with doctors, Genfit has found that there isn’t an incentive to screen more patients for NASH as there are currently no approved drugs for the disease.
“Once the first drug becomes available, there will be a significant increase in the need for a diagnostic,” he said and likely echo the sort of mutation and biomarker tests that are now so common for oncology drugs.
Genfit is already making NIS4 available in research settings, through a partnership with diagnostics giant LabCorp—“essentially, we’re sending it to all our competitors,” Prigent said—but it has big plans for the test. It hopes to turn it into a monitoring test to track how patients do on NASH drugs once they’re approved.
“From a payer standpoint, it’s important that once drugs are on the market, that you can actually say whether they have the intended impact. Of course, today, the only way to do that is to do multiple biopsies, which nobody’s going to accept,” he said.
For the time being, Genfit hopes the test will help drug developers cut down on the number of biopsies it needs to carry out to get patients into clinical trials. It’s an unavoidable part of developing NASH treatments as the FDA requires biopsies to screen patients for, and measure clinical endpoints in, phase 3 studies. And it’s not a perfect tool—about three out of every 10 patients screened for a NASH trial ends up qualifying for that trial, Prigent said.
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“All those biopsies, by definition are unnecessary.”
At AASLD, Genfit presented the latest of several posters showing how NIS4 performs in various patient populations. This study assessed how NIS4 did against other tests in catching at-risk NASH inpatients with Type 2 diabetes. It found that these patients had a higher risk of NASH that required treatment and “demonstrates high accuracy to non-invasively identify those who should be considered for intervention.”
“You don’t have such a thing as a pure NASH patient. These patients have diabetes, they’re obese or maybe overweight, they have high cholesterol. You have to show your test is going to be unaffected by those different comorbidities,” Prigent said.
In the future, Prigent envisions tests like NIS4 being used to measure endpoints in NASH clinical trials. But he acknowledged that that's further down the road. It will take time for doctors to get comfortable with NIS4 in a real-life setting; they will likely use it in conjunction with a series of other tests to diagnose NASH.
"Over time, it’s possible they will feel comfortable and say, 'OK, I’m going to use only one test and it’s going to be good enough for me,'" Prigent said. "But before [NIS4] can be used in a regulatory setting, it will require further validation and proof."