NASH frontrunner Intercept Pharma is well on its way to market—it’s already filed Ocaliva for FDA review and will soon follow up with a filing in Europe. But in the meantime, it’s crunching data from a pivotal trial to help advance the field of NASH diagnostics.
The company presented a secondary analysis of its Regenerate study, a phase 3 trial that pitted two doses of Ocaliva against placebo in 2,480 people with nonalcoholic steatohepatitis (NASH). The analysis found that treatment with Ocaliva, also called OCA, “resulted in early and consistent improvements across several inexpensive and readily available non-invasive measures of fibrosis and NASH, suggesting serum tests may be useful for monitoring early treatment response.”
The analysis looked at all 18 months of data but patients saw improvements as early as six months into treatment. The tests included blood-based tests as well imaging-based ones, such as transient elastography, an ultrasound-based measure of liver stiffness. The hope is that companies such as Intercept and their academic partners can validate the tests to supplement the use of liver biopsy to evaluate NASH treatments.
“We took patients within Regenerate, regardless of what they had treated with, whose fibrosis had improved by at least one stage, who had not changed in their fibrosis stage, and who had worsened by at least one stage,” Gail Cawkwell, M.D., Ph.D., SVP, medical affairs, safety and pharmacovigilance at Intercept, told FiercePharma.
Fibrosis, or scarring, is seen on a biopsy and measured on a scale of discrete numbers, like 0, 1 and 2. But this approach can be clumsy as, in Cawkwell’s words, it “puts people into big-box categories."
“The difference between [stage 1 and stage 2] could be quite big. There could be a lot of variability in there, so the ability to see improvement can really lag behind because a one-stage improvement could be quite a big leap,” she said.
The analysis found that in patients whose fibrosis stage improved, placebo patients improved a little, and Ocaliva patients improved “quite a bit more, linearly and continuously over time,” she said. For those whose fibrosis stage stayed the same, placebo patients logged no change in their noninvasive test scores, but the scores of the Ocaliva patients improved over time.
It probably points to some positive effects from the drug that can’t be captured by liver biopsy, the current gold standard, Cawkwell said. What’s more, liver biopsy is invasive, expensive and subjective—a pathologist’s findings depends on which part of liver the sample was from and on the pathologist’s own experience.
Doctors have figured this out—in its conversations with healthcare professionals, Intercept has found that they are increasingly using noninvasive tools to help them with diagnosing and staging NASH patients.
“They are reserving biopsy for smaller numbers of patients where the results are perhaps ambiguous or where they’re concerned that perhaps something else is going on besides NASH,” Cawkwell said.
Clinical R&D just hasn’t caught up.
To that end, Intercept is mining its dataset with experts, including a pair of NASH-focused consortia in the U.S. and Europe, to review and validate noninvasive tests. The rest, Cawkwell said, is up to the FDA.
“As of now, for phase 3 studies, FDA requires the biopsy. It’s in their draft guidance, it’s what they want to see,” she said. “It’s possible that as the world migrates and the tests reach a degree of validation, that FDA may change, but that will be up to FDA to figure out."