Galmed Pharmaceuticals Shows Aramchol's Promise Against Biliary Fibrosis In PSC Models

Galmed Pharmaceuticals Shows Aramchol's Promise Against Biliary Fibrosis In PSC Models



Galmed Pharmaceuticals Ltd., based in Tel Aviv, has recently made significant strides in the fight against biliary fibrosis, a condition often linked with serious liver diseases such as primary sclerosing cholangitis (PSC). Its promising drug candidate, Aramchol, has demonstrated notable anti-fibrotic effects in pre-clinical studies, particularly in mouse models.

Understanding Aramchol and PSC



Aramchol functions as a saturated fatty acid derivative that inhibits stearoyl-CoA desaturase-1 (SCD1). This inhibition plays a critical role in regulating fatty acid metabolism, particularly in liver cells. PSC, a rare liver disorder characterized by inflammation and fibrosis of bile ducts, poses a significant risk for patients, including the development of bile duct cancer.

Recent experiments have showcased how Aramchol not only diminishes the detrimental effects of biliary fibrosis but also prevents its onset in PSC models. Specifically, the treatment reduced the expression of critical fibrotic markers, including plasminogen activator inhibitor-1 and certain hepatic stellate cell activation markers, effectively curbing the progression of liver damage caused by PSC.

Efficacy and Mechanism



In these studies, Aramchol exhibited a dose-dependent reduction in the harmful expression of liver fibrosis pathways. Notably, the drug achieved a two-fold significant inhibition of TGFβ-induced fibrosis pathways, a major contributor to liver inflammation and damage. Furthermore, Aramchol enhanced peroxisome proliferator-activated receptor (PPAR) signaling, a pathway that helps regulate fat metabolism and inflammation in the liver.

The findings are especially important as PSC bears a 20% risk of progressing to cholangiocarcinoma (CCA), a severe complication with a grim prognosis. This is primarily due to the combination of late diagnosis and a lack of effective treatments available for advanced cases of cancer. The fibrotic environment promoted by PSC is known to exacerbate tumor growth, complicating treatment efforts.

Clinical Implications



The results from the investigational studies support Aramchol's potential role in treating not only biliary fibrosis but also hepatic cancers associated with PSC. A previously conducted phase IIb trial (ARREST) revealed a significant improvement in liver fibrosis among participants treated with Aramchol. This is particularly crucial as about 80-90% of hepatocellular carcinomas (HCC) arise in the presence of liver fibrosis or cirrhosis.

With a well-documented safety profile through multiple clinical trials, the rationale for advancing Aramchol into further clinical studies with PSC patients is compelling. Experts, including Dr. Sayed Obaidullah Aseem from the Stravitz-Sanyal Institute, have emphasized that the attenuation of biliary fibrosis is of utmost importance, as current treatment options for PSC are limited and urgently needed.

Future Prospects



Galmed's President and CEO, Allen Baharaff, have reinforced the importance of these new findings that underscore the anti-fibrotic activity of Aramchol across various preclinical models. Given the promising results observed in clinical studies concerning other liver diseases, there is substantial optimism that this could enable the company to progress towards Phase 2/3 clinical studies specifically targeting GI oncology.

Overall, these findings about Aramchol represent not only a breakthrough in the understanding of PSC treatment but also provide hope for patients suffering from this challenging condition. With plans for further investigation into its effects on biliary and hepatic fibrosis, the future of Aramchol looks promising in the quest for effective treatment options against liver diseases.

As we await further findings, this development reaffirms the critical need for innovative treatments for liver conditions and reinforces Galmed's commitment to advancing hepatology research and therapeutics.

Topics Health)

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