Dr. Falk Pharma announced positive results from its pivotal Phase 3 trial evaluating norucholic acid (NCA) in patients with primary sclerosing cholangitis (PSC), marking a potential breakthrough for a disease that currently has no approved pharmaceutical treatments.
The double-blind, placebo-controlled NUC-5 trial enrolled 301 patients with PSC who received either 1,500 mg of NCA or placebo. After 96 weeks of treatment, the study met its primary endpoint, with a significantly higher proportion of NCA-treated patients achieving partial normalization of alkaline phosphatase (ALP) levels and showing no worsening of disease stage on histology compared to the placebo group.
Significant Clinical Improvements
At the 96-week analysis, 15.1% of patients receiving NCA achieved the primary endpoint compared to only 4.2% of placebo patients (p = 0.0048). The key secondary endpoint, which used modified Nakanuma staging, was achieved by 15.1% of NCA patients versus 5.1% of placebo patients (p = 0.0086).
Perhaps most importantly, NCA treatment demonstrated the ability to improve liver histology, with 25.2% of treated patients showing improvement by at least one Ludwig stage compared to 10.5% of placebo patients (p = 0.0217). Disease progression was also significantly reduced, with worsening by at least one Ludwig stage observed in only 20.3% of NCA patients compared to 40.4% of placebo patients (p = 0.0069).
The safety profile was favorable, with similar rates of adverse events and serious adverse events between the NCA and placebo groups.
A Watershed Moment for PSC Treatment
PSC is a rare, progressive disease characterized by immune system attacks on the bile ducts in the liver, leading to fibrosis and scar tissue formation. Patients face serious complications including bile duct, liver, or colorectal cancer, with many eventually progressing to liver cirrhosis. Currently, liver transplantation remains the most effective treatment option.
"Finding a medicine that effectively treats PSC has been a challenge in the field of hepatology for decades," said Prof. Michael Trauner, Head of the Division of Gastroenterology and Hepatology at the Medical University of Vienna, Austria and principal investigator of the trial. "After so many disappointments in this space, the first positive results from a phase 3 study on PSC is a watershed moment for people with PSC, their families, physicians and the entire PSC community. The results of this study will not only advance patient care but will also give researchers new insights into the disease itself."
Dr. Kai Pinkernell, Managing Director Science and Innovation for Dr. Falk Pharma, highlighted the significance of the trial: "We are very excited about the positive results of the NUC-5 trial, which was the largest clinical trial on PSC to date which compared biopsies from patients before and after treatment. A trial of this duration and involvement is a major undertaking, and we thank all of the participating patients, investigators, and trial staff for their dedication to this trial."
Mechanism of Action and Trial Design
Norucholic acid is an engineered bile acid derivative with unique properties that distinguish it from endogenous bile acids. Unlike natural bile acids, NCA undergoes minimal amidation with glycine or taurine, allowing it to be absorbed from bile by cholangiocytes and subsequently re-secreted into bile by hepatocytes in a process called cholehepatic shunting. This mechanism, combined with potential anti-inflammatory and anti-fibrotic effects, is believed to provide protective benefits in PSC.
The NUC-5 trial specifically enrolled patients with biopsy-confirmed PSC and elevated ALP levels at least 1.5-fold greater than the upper limit of normal. The trial is ongoing, with patients continuing to receive either NCA or placebo for an additional 96 weeks, for a total treatment duration of 192 weeks. Patients who complete the full double-blind treatment period will have the option to receive open-label NCA for up to 72 additional weeks.
The topline results from the NUC-5 trial will be presented during the Late Breaker session on Saturday, May 10, 2025, at the European Association for the Study of the Liver (EASL) Congress in Amsterdam.
Implications for the Future of PSC Treatment
The positive results from this Phase 3 trial represent a significant advancement in the treatment landscape for PSC, a disease that has seen numerous failed clinical trials in the past. If approved, norucholic acid would become the first pharmaceutical treatment specifically indicated for PSC, potentially reducing the need for liver transplantation in some patients.
Dr. Falk Pharma, a family-owned business with global operations, has been developing treatments for gastrointestinal and hepatobiliary disorders for over 60 years. The company specializes in digestive and metabolic medicine, with a focus on conditions like inflammatory bowel disease, eosinophilic esophagitis, and primary biliary cholangitis.
With headquarters and R&D facilities in Freiburg, Germany, Dr. Falk Pharma employs approximately 1,400 individuals globally and manufactures its pharmaceutical products at sites throughout Europe, including Germany, France, Italy, and Switzerland.
