Namodenoson study for severe fatty liver disease cleared for US
Phase 2B clinical trial begins accepting adults in 2022 in Europe, Israel
Can-Fite BioPharma has been approved to enroll U.S. patients in its ongoing Phase 2b clinical trial of the oral treatment candidate namodenoson in people with metabolic dysfunction-associated steatohepatitis (MASH), a severe form of fatty liver disease.
The Phase 2b study (NCT04697810), which recruited its first participant in January 2022, has been enrolling adults with MASH and liver scarring at sites in Europe and Israel. With the U.S. Food and Drug Administration (FDA)’s recent clearance of the company’s investigational new drug application (IND), sites in the U.S. can also open, but none are listed on the trial page yet.
“The IND activation for the treatment of MASH patients with namodenoson, opens the gate for the enrollment of U.S.-based patients and will contribute to the heterogeneity [diversity] of the population of this study,” Motti Farbstein, Can-Fite’s CEO and chief financial officer, said in a company press release.
The company hopes to be able to wrap up trial enrollment “in the next few months,” with U.S. recruitment, Farbstein said.
Fatty liver disease refers to a group of conditions wherein fatty deposits accumulate abnormally in the liver. MASH, which was formerly known as nonalcoholic steatohepatitis, or NASH, arises when this buildup leads to liver inflammation, which gives way over time to fibrosis, or scarring, and then cirrhosis, where irreversible scarring impairs the liver’s function. Left unmanaged, liver failure or liver cancer may result.
What is namodenoson?
Namodenoson is designed to activate A3 adenosine receptors (A3AR), cell surface proteins that mediate the effects of the signaling molecule adenosine.
A3ARs are found at low levels under normal conditions, but their production is increased in inflammatory and cancer cells. In MASH, they’re found at higher than normal levels on the surface of diseased liver cells, but not healthy ones, according to Can-Fite.
This A3ARs increase associated with disease states is thought to be associated with anti-inflammatory, anti-cancer, and protective effects in the liver. By activating these receptors, namodenoson may help slow the progression of MASH, Can-Fite maintains.
Treatment with it has been shown to reduce MASH disease activity, lower liver inflammation, and ease fibrosis in preclinical models of the disease. And since A3ARs are mainly on diseased cells, the medication may have a favorable safety profile by avoiding unintended effects in healthy cells.
A Phase 2a trial (NCT02927314), which was launched in 2017, tested two oral doses of namodenoson (12.5 and 25 mg, taken twice daily) against a placebo in 60 adults with fatty liver disease, some of whom had MASH, over three months.
The therapy, particularly the 25 mg dose, tended to be or was significantly superior to a placebo at easing liver inflammation and fibrosis and at lowering liver fat content. It also had a good safety profile.
The Phase 2b trial is further assessing namodenoson’s safety and effectiveness in up to 140 adults with biopsy-confirmed MASH and liver fibrosis. the participants are randomly assigned in a 2:1 ratio to receive either oral namodenoson (25 mg) or a placebo, twice daily (once every 12 hours) for 36 weeks, or a little more than eight months.
The study’s main efficacy goal is to evaluate the proportion of participants who achieve a clinically meaningful reduction in MASH severity, as reflected by a 2-point or greater improvement on the Nonalcoholic Fatty Liver Disease activity score (NAS). NAS is a composite score that considers several MASH-associated liver biopsy findings.
The occurrence of side effects is another main goal of the trial.
Secondary goals include changes in blood levels of the liver enzyme alanine transaminase, a marker of liver damage, and steady-state blood levels of namodenoson. Changes in blood levels of other liver enzymes, metabolic markers, body weight, measures of liver fibrosis and MASH will also be evaluated.
“We are committed to improve the lives of MASH patients and based on the efficacy of the drug in the Phase IIa study, we are proud to develop a new potential treatment to address this disease,” Farbstein said.
Namodenoson also is being evaluated to treat certain cancers of the liver and pancreas.
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