Dr. Falk Pharma reports successful phase 3 trial results for norucholic acid in primary sclerosing cholangitis

Freiburg, May 7th, 2025 - Dr. Falk Pharma, a company with a strong focus on digestive and metabolic diseases, has announced promising outcomes from its NUC-5 study involving norucholic acid (NCA) for treating primary sclerosing cholangitis (PSC). This phase 3 trial marks a significant milestone in the quest to find an effective treatment for PSC, a chronic liver disease with no approved pharmaceutical remedies currently available.

Primary sclerosing cholangitis is a progressive illness attacking the bile ducts in the liver, leading to fibrosis and, consequently, the formation of scar tissue. Numerous patients with PSC are at risk of developing bile duct, liver, or colorectal cancer. Often, these individuals progress to liver cirrhosis, and liver transplantation remains the only effective treatment option.

The NUC-5 trial is a pivotal phase 3 study designed as a randomized, double-blind, placebo-controlled trial involving 301 patients diagnosed with PSC. These participants were administered either 1,500 mg of NCA or a placebo over 192 weeks. The analysis of data after 96 weeks of treatment highlighted that a more significant portion of patients on NCA achieved the primary endpoint than those on placebo. This primary endpoint was a combined measure of partial normalization of blood levels of alkaline phosphatase, a liver enzyme linked to PSC, alongside no worsening of disease stage based on histological examination.

The analysis revealed that 15.1% of patients treated with NCA met the primary endpoint, compared to just 4.2% in the placebo group. Additionally, significant improvement was noted in secondary outcomes, where NCA again showed superiority. Notably, NCA treatment improved the condition by at least one Ludwig stage for 25.2% of participants, a stark contrast to 10.5% seen in the placebo group. Conversely, worsening by at least one Ludwig stage was observed in 40.4% of the placebo group, compared to only 20.3% of those on NCA. Blood levels of multiple liver enzymes improved in patients receiving NCA but not in those on placebo.

These findings are set to be presented during the Late Breaker session at the 2025 EASL Congress in Amsterdam. The trial's outcomes highlight a breakthrough in hepatology, given the lack of successful treatments in this area over the years. Prof. Michael Trauner, the principal investigator, emphasized the significance of these results, noting their potential to transform patient care and further the understanding of PSC.

Dr. Kai Pinkernell, Managing Director of Science and Innovation at Dr. Falk Pharma, expressed excitement over the trial’s success, acknowledging the dedication of patients and researchers involved. This trial represents the largest clinical trial on PSC to date and involved a complex comparison of biopsies before and after treatment.

Norucholic acid, an engineered bile acid derivative, exhibits unique properties, allowing it to be absorbed and re-secreted by liver cells, potentially offering anti-inflammatory and anti-fibrotic benefits. Previous phase 2 trials have already demonstrated NCA’s ability to significantly reduce alkaline phosphatase levels in the blood, further supporting its therapeutic promise.

The NUC-5 trial is ongoing, with patients continuing to receive either NCA or placebo for another 96 weeks. Upon completion of all 192 weeks of the double-blind study, participants will have the option to enter a 72-week open-label treatment phase with NCA.

Dr. Falk Pharma, a family-owned pharmaceutical firm with a global footprint, has been at the forefront of gastrointestinal and hepatobiliary disorder treatment development for over six decades. With its headquarters in Freiburg, Germany, the company employs a significant workforce dedicated to improving therapeutic practices and enhancing patient well-being.