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Phase 2 trial called FLINT. In FLINT, the levels went back down after treatment with statins, the standard medicine for high cholesterol.
NGM has also reported at EASL that a similar up-and-down effect occurred in a preclinical trial with NGM-282, using monkeys as test subjects, also taking statins. A human study is underway; NGM has data on 15 people so far and says the effect is similar to that in monkeys.
But doctors are keeping an eye on the cholesterol data; regulators are likely to take note, too, and weigh the added risk against the benefit of treating a rapidly growing unmet medical need. “Most patients with fatty liver disease will die of heart disease, not liver failure,” said Jaideep Behari, founder of the University of Pittsburgh Medical Center’s Fatty Liver Clinic. “So a medicine that increases cardiovascular risk is obviously concerning, especially if you have to take it long-term.”
At some point, NGM president Jeff Jonker said NGM will explore a version of NGM-282 that would require less frequent injections. For now, though, the daily injections the drug requires gives pause to University of California, San Francisco director of pediatric hepatology Philip Rosenthal. Many NASH patients are diabetic, as well, so they might have two daily injections to deal with. “I’m sure patients will love that,” said Rosenthal with a note of sarcasm.
Jonker said that strong results would “overcome any hesitancy” about a daily injection, and that people already taking daily shots for diabetes would be “familiar” with the regimen. (NGM declined to discuss pricing, saying it was too early.)
NGM’s next step: Start what they’re calling a “Phase 2b” trial to test doses of NGM-282 lower than 3 mg. The study will be designed to test not just if NGM-282 can trigger the short-term indirect signs of fibrosis reversal that cropped up in the Phase 2 study, but also if it can lead to longer-term changes, taken from a liver biopsy.
Jonker declined to say how long the Phase 2b patients will stay on the drug, or whether it will be designed to lead directly to a request for FDA approval. The design of the trial, Jonker said, “will permit the assessment of the full impact of the compound after an appropriate duration of treatment.”