- Aramchol, an SCD1 inhibitor, significantly attenuates and prevents biliary fibrosis in mouse models of primary sclerosing cholangitis (PSC)
- Aramchol treatment leads to significant inhibition (2-fold, p<0.05) of TGFβ-induced hepatic fibrosis pathways while upregulating peroxisome proliferator activated receptor (PPAR) signaling
- Aramchol’s effect in the prevention and treatment of biliary and hepatic fibrosis, provides the rationale for assessing Aramchol in further clinical studies in patients with fibrosis driven liver cancers
TEL AVIV, Israel — Galmed Pharmaceuticals Ltd. (NASDAQ: GLMD) (“Galmed” or the “Company”), a clinical-stage biopharmaceutical company for cardiometabolic diseases and GI oncological indications announced today results showing significant effects of Aramchol in pre-clinical models of primary sclerosing cholangitis (PSC).
Fibroinflammatory cholangiopathies, such as PSC and primary biliary cholangitis (PBC), are characterized by cholestatic injury, inflammation and fibrosis-induced obstruction of ducts, driving disease-related complications.
Aramchol, an SCD-1 inhibitor, both attenuated and prevented biliary fibrosis in mouse models of PSC. Aramchol significantly reduced, in a dose-dependent manner, the increased expression of the fibrotic marker plasminogen activator inhibitor-1 and hepatic stellate cell-activating genes (VEGFA and PDGFB) in TGFβ-activated transformed human cholangiocyte cells (H69) and mouse large biliary epithelial cells (MLEs). Aramchol led to a significant inhibition of TGFβ-induced hepatic fibrosis pathways while upregulating peroxisome proliferator activated receptor (PPAR) signaling.
PSC carries a 20% lifetime risk for the development of colangiocarcinoma (CCA). CCA is the second-most prevalent primary malignancy in the liver. CCA has a poor prognosis with the majority of CCA patients surviving for less than a year, due to a combination of late diagnosis and the lack of efficient therapies for advanced stages. The PSC fibrotic environment is tumor-promoting and in its turn, CCA triggers a strong fibrotic reaction which contributes to the lack of efficacy of therapy.
As previously announced, in a randomized, double-blind, placebo-controlled phase IIb trial (ARREST) and an open label extension of a phase III study (ARMOR), Aramchol demonstrated significant improvement in liver fibrosis. Liver fibrosis is strongly associated with Hepatic Cellular carcinoma (HCC) with 80–90% of HCCs developing in fibrotic or cirrhotic livers. The fibrotic environment in which HCC arises exerts a major influence on tumor development and growth.
Aramchol’s effect in the prevention and treatment of hepatic and biliary fibrosis, along with its excellent safety profile in clinical trials, provide the rationale for assessing Aramchol in further clinical studies in patients with biliary fibrosis, particularly PSC, and hepatic cancers, such as CCA and HCC.
Sayed Obaidullah Aseem, M.D., Ph.D., in Stravitz-Sanyal Institute for Liver Disease & Metabolic Health Virginia Commonwealth University commented, “Aramchol attenuates biliary fibrosis in two mouse models of biliary fibrosis along with antifibrotic effects in cholangiocytes, myofibroblasts and hepatocytes. These observations combined with its excellent clinical trial safety data provide the rationale for further clinical studies of Aramchol in patients with biliary fibrosis, in particular PSC, where treatments are desperately needed.”
Allen Baharaff, President and CEO of Galmed Pharmaceuticals commented, “The new findings reinforce the anti-fibrotic activity of Aramchol previously observed in a wide range of pre-clinical models, in addition to the known effects in liver fibrosis. Together with the robust anti-fibrotic effects of Aramchol previously demonstrated in clinical studies of patients with NASH and advanced fibrosis, these findings could potentially enable Galmed to transition to Phase 2/3 clinical studies with Aramchol in GI oncology indications.”
About Galmed Pharmaceuticals Ltd.
We are a biopharmaceutical company focused on the development of Aramchol. We have focused almost exclusively on developing Aramchol for the treatment of liver disease and we are currently seeking to advance the development of Aramchol for oncological indications outside of NASH and fibrosis. In addition, as part of our growth strategy, we are actively pursuing opportunities to expand and diversify our product pipeline specifically targeting cardiometabolic indications and other innovative product candidates that align with our core expertise in drug development.
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