Akero Therapeutics announced the ongoing Phase 2a BALANCED study of AKR-001 is being expanded to include an additional cohort of subjects with non-alcoholic steatohepatitis (NASH) who have compensated cirrhosis (F4), Child-Pugh Class A.
Thirty NASH subjects, demonstrated at baseline by liver biopsy to have cirrhosis with a fibrosis score of 4, will be randomized 2:1 to receive either 50 mg of AKR-001 or placebo for 16 weeks. The primary objective of the expansion cohort is to assess safety and tolerability of treatment with AKR-001 in NASH patients at greatest risk of progressing to end-stage liver disease. The selection of the 50 mg dose for this cohort is based on modeling of data from the Phase 1b trial in Type 2 diabetes as well as availability of drug product.
"Cirrhotic patients with stage 4 fibrosis present a significant unmet medical need in NASH because of the risk of decompensation and liver failure, where liver transplant becomes the only treatment option," said Kitty Yale, chief development officer of Akero. "AKR-001 may be able to help this vulnerable population."
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NASH (non-alcoholic steatohepatitis) is a serious form of NAFLD (non-alcoholic fatty liver disease) and is estimated to affect 17 million Americans. NASH is closely linked to the obesity and diabetes epidemics seen around the world. NASH is characterized by an excessive accumulation of fat in the liver that causes stress and injury to liver cells, leading to inflammation and fibrosis, which can progress to cirrhosis, liver failure, cancer and eventually death. The progressive damage to the liver associated with NASH closely resembles damage caused by excessive alcohol consumption or viral infections, and the disorder is a leading cause of liver transplants in the US and Europe.
AKR-001 is an Fc-FGF21 fusion protein that has been engineered to mimic the biological activity profile of native FGF21, an endogenous hormone that regulates lipid and energy metabolism, and is secreted throughout the body to alleviate cellular stress. Observations from clinical trials of AKR-001 and other FGF analogs point to AKR-001's potential to reduce liver fat, cellular stress, inflammation and fibrosis in people with non-alcoholic steatohepatitis (NASH), as well as to improve risk factors of cardiovascular disease, the principal cause of death among NASH patients.