Aramchol Has Significant Anti-fibrotic Effects in IPF Mouse Model
Aramchol, an investigational therapy for idiopathic pulmonary fibrosis (IPF), demonstrated significant anti-fibrotic effects in a mouse model.
The therapy, developed by Galmed Pharmaceuticals, is currently being evaluated in a Phase 3 clinical trial in people with nonalcoholic steatohepatitis, or NASH, a type of fatty liver disease characterized by inflammation and fat accumulation in the liver.
Aramchol partially inhibits the activity of a liver enzyme called stearoyl coenzyme A desaturase 1 (SCD1). In preclinical models and NASH clinical trials, the treatment has been shown to have direct anti-fibrotic activity. Its effects on fibrosis are mediated by a decrease in steatosis, or abnormal fat retention, as well as on cells that produce collagen — the main protein found in scar tissue.
“The new findings, together with the robust anti-fibrotic effects demonstrated in clinical studies of patients with NASH and advanced fibrosis could potentially enable Galmed to quickly transition to Phase 2/3 clinical studies with Aramchol in indications with unmet need and faster development pathways,” Allen Baharaff, co-founder, president, and CEO of Galmed, said in a press release.
The company tested Aramchol in a validated mouse model of induced IPF, a condition marked by progressive fibrosis, or scarring, in the lungs due to an unknown cause.
The mouse model was established by exposing mice to bleomycin, a cancer medication that triggers fibrosis and mimics typical features of the human disease.
Treatment with Aramchol led to statistically significant improvements in fibrosis that were comparable to those seen with pirfenidone, an approved IPF therapy marketed as Esbriet by Genentech.
Aramchol improved several fibrosis markers, including hydroxyproline, an indicator of collagen deposition in fibrotic tissue. Improvements were also seen in the Ashcroft score — a method of quantifying the severity of lung fibrosis — as well as in the levels of type I collagen, and SMA, a marker of activated pro-fibrotic cells.
The company also evaluated Aramchol in a mouse model of inflammatory bowel disease — a group of conditions characterized by chronic inflammation of the digestive tract. Intestinal fibrosis is a common complication due to the accumulation of scar tissue in the intestinal wall. Aramchol led to significant clinical improvements, with reduced inflammation and intestinal structural changes.
Galmed is currently assessing Aramchol’s anti-fibrotic effects on the kidneys and skin.
“I am excited with today’s news showing that established data about the role of SCD1 in lipid metabolism and fibrosis in the liver, is being replicated in other organs,” said Baharaff. “Today we show that Aramchol’s effect is evident in other organs, such as lung and gastrointestinal tract and may be as substantial as the one observed in the liver.”
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