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NorthSea Therapeutics B.V. have announced the dosing of the first patient in its Phase 2a clinical trial of Orziloben (NST-6179) in intestinal failure-associated liver disease (IFALD), an orphan liver disease affecting individuals on prolonged intravenous (parenteral) nutrition (PN).
The trial is a randomised, double-blind, Phase 2a, placebo-controlled study, which will be conducted at multiple sites across North America. It is designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of Orziloben in adult subjects with IFALD. The readout of the trial is anticipated in H2 2025.
Rob de Ree, NST’s CEO, said: "Dosing the first patient in our Phase 2a trial for Orziloben in IFALD is a significant achievement for NorthSea Therapeutics, and is a testament to our commitment to advance innovative treatments for liver diseases. There is a critical need for effective therapies in IFALD as, to date, there are no drug therapies approved to treat this orphan indication. We believe Orziloben has the potential to make a substantial impact in addressing this unmet medical need."
IFALD is a complex condition, characterised by the development of hepatic inflammation, cholestasis and steatosis, in patients with intestinal failure and/or short bowel syndrome. It is known to be associated with prolonged administration of PN. One major concern for patients with the condition is the development of hepatic fibrosis, which can progress to cirrhosis and liver failure.
Professor Palle Bekker Jeppesen, Head of the Department of Intestinal Failure and Liver Diseases at Rigshospitalet in Copenhagen, added: “Orziloben has shown consistently robust efficacy in several pre-clinical models, and has demonstrated a strong preventative effect on important disease pathophysiology components, such as cholestasis and fibrosis. If these impressive pre-clinical effects translate to clinical effects, Orziloben has the potential to become an effective therapeutic for intestinal failure patients who currently have limited treatment options.”
Preclinical studies have demonstrated the efficacy of Orziloben in preventing severe cholestasis, fibrosis, and other key markers of liver damage in models where PN was administered. In one pre-clinical model of PN-induced liver injury, Orziloben treatment completely prevented severe cholestasis and the development of fibrosis. Orziloben was also shown to prevent the pronounced increase in markers of liver damage in another in vivo model of PN in combination with an inflammatory stimulus (endotoxin). Furthermore, Orziloben significantly reduced the number of myofibroblasts, the main collagen producing cell in the liver, in addition to hepatic inflammation and steatosis in a model of established fibrosis. The unique ability of Orziloben to target multiple pathogenic components of IFALD, and its potential for oral dosing, make it a promising candidate for the treatment of PN-induced liver disease, as well as other liver disease indications.