Clinical Trial for Norucholic Acid – Latest Results
Norucholic Acid (NCA) Clinical Trial
News from the International Liver Congress (EASL) 2025
Ask the Expert 17 May 2025
Watch Dr Trivedi answer your questions about this clinical trial:
Dr. Falk Pharma, a pharmaceutical company based in Germany, has announced long-awaited results of its pivotal Phase 3 clinical trial assessing norucholic acid (NCA)* as a treatment for PSC. This is the furthest a drug has progressed in PSC medicine development with positive results.
Key information in this trial was taken from liver biopsies taken at the beginning and after 2 years of treatment (to grade changes to the level of liver damage) and liver blood tests (specifically, alkaline phosphatase, ALP) which is a marker of bile duct injury.
The measure of how well NCA performed was a combination of ALP decrease (as seen in the blood tests) and liver damage not progressing (as seen in biopsy readings). This was called the ‘combined primary endpoint’.
Professor Michael Trauner reported that after 96 weeks of taking NCA, 15.1% had no worsening to the damage in their livers and partial normalisation of ALP, compared to 4.2% who took the placebo (inactive drug). They concluded that NCA is significantly superior to the placebo for certain patients. Improvements in liver biopsy readings by 1 Ludwig stage** was observed for a quarter (25.2%) of those on NCA versus 10.5% in the placebo group. This represents not only not only stopping more scarring, but also starting to reverse it. Only 20.3% of the NCA group worsened by at least 1 Ludwig stage compared with 40.4% in the placebo group.
Biopsies
Not everyone in the trial had their second biopsy. The team dealt with this by classing this missing data as 'not responding' to NCA. However, when those participants were removed from the analysis, they found that 21.7% had definite improvements to the scarring in their livers and partial normalisation of ALP compared to 5.7% on the placebo (inactive drug). This means that NCA was superior to placebo for 1 in 5 participants.
Ursodeoxycholic acid (UDCA)
Some participants in this trial were also taking UDCA. Professor Trauner reported higher response rates when participants did not take UDCA compared to those who did. The chart below shows that 12.7% of participants taking NCA+UDCA met the primary endpoint (partial normalisation of ALP and no worsening of liver damage), and 23.4% for those taking NCA (and no UDCA). This suggests (but we don’t know for sure) that UDCA may somehow reduce the effect of NCA.
What is NCA?
NorUrso is a modified version of UDCA, and alters bile acids, which are thought to be responsible for bile duct and liver damage in PSC.
Can people with PSC get NCA now?
No. These results, while promising for a subgroup of PSC patients, do not automatically mean that NCA will be available very soon. The study will continue to gather longer term data on NCA. All medicines must have enough data to show they are safe and effective, be approved by regulators and then reviewed for cost effectiveness before they can be prescribed. We will work with the regulators to help ensure that safe and effective drugs are made available to those who need them.
Does this news mean other trials will stop?
No. There are other treatments and drugs to help with symptoms undergoing testing right now. They each work in different ways. The likelihood is that we will need to take several drugs one day and we must continue to develop them.
Ask the Expert
Dr Palak Trivedi will join us in a special Ask the Expert in a couple of weeks (date to be confirmed) giving us a fantastic chance to ask questions and find out more about NCA.
*NCA was previously known as NorUrso
** They graded the biopsies using a scale (called the Ludwig scale) that has stages going from 0 to 5.