This is promising news.
I first heard about Norudca when I got diagnosed more than 10 years ago. Hopefully the long wait is over and this turns out to be a real cure or treatment.
List of accepted late-breaker EASL abstracts:
Here is the Google AI summary:
Michael Trauner will be presenting on Norucholic acid for the treatment of primary sclerosing cholangitis at the EASL Congress 2025. This oral presentation, titled “Norucholic acid for the treatment of primary sclerosing cholangitis: 96-week analysis of a pivotal phase 3 trial” will be part of the EASL Congress in Amsterdam. The presentation is scheduled to take place on May 7-10, 2025
I’m convinced that the clinical trial phase 3 results are going to be positive.
The big question is when is Norudca going to be available (in the pharmacy near you).
In Europe this may happen soon since the company operates in Europe and trials were done in Europe.
EA pharma acquired licensing rights in Japan, so presumably it will be available in Japan in the near future.
But I think there is no US company yet that has the licensing rights. It cannot be sold in the US if there is no US company with the necessary rights (could be local branch of dr falk).
US based patients may need to travel to Europe to get access to Norudca, though I’m not sure if Norudca would be available outside of the national healthcare system.
I haven’t seen yet any update from the oral presentation, but here is the press release summary:
(It is declared as success, but to me it looks like e.g. Vancomycin works better..15% achieved primary endpoint vs 4% in placebo group..not very impressive results). No information when this would be approved.
“At the primary data analysis after 96 weeks of treatment, the primary endpoint of combined partial normalization of blood levels of a liver enzyme linked to PSC (alkaline phosphatase) and no worsening of disease stage on histology was achieved by a statistically significantly greater proportion of patients receiving NCA than placebo. Significant superiority of NCA was also observed in multiple secondary endpoints. "
“At week 96, 15.1% of patients receiving NCA achieved the primary endpoint compared to 4.2% of placebo patients (p = 0.0048). Similarly, 15.1% of NCA patients versus 5.1% of placebo patients achieved the key secondary endpoint (p = 0.0086). NCA treatment led to improvement by at least 1 Ludwig stage for 25.2% of NCA patients compared to 10.5% of placebo patients (p = 0.0217). Furthermore, worsening by at least one Ludwig stage was observed in 40.4% of placebo patients compared to 20.3% of NCA patients (p = 0.0069). Blood levels of multiple liver enzymes improved under NCA but not placebo. NCA was well tolerated, with similar rates of serious adverse events between the two arms.”
Yeah, that doesn’t look great. Worth mentioning is that the “primary endpoint” they’re referring to is just a ALP being <1,5x normal range and no progression in terms of liver fibrosis stages. Only seeing 15% of patients normalize their ALP sounds like quite a failure.
Also, just looking at liver fibrosis stages is quite misleading for short studies (this one was just 22 months). As PSC is slow progressing and there only are 4 stages, it will of course take many years between each stage.
Background and aims: Primary sclerosing cholangitis (PSC) is a chronic inflammatory, fibro-obliterative cholestatic liver disease lacking effective medical therapy. The semi-synthetic bile acid derivative norucholic acid (NCA) is resistant to amidation, allowing it to undergo cholehepatic shunting. This results in bicarbonate-rich hypercholeresis and cholangiocyte protection, as well as potential direct anti-inflammatory and immunomodulatory effects. Here, we
report the results from the pivotal phase 3 trial of NCA in PSC over 96 weeks (NCT03872921).
Method: In this randomized, placebo (PBO)-controlled, double-blind (DB) phase 3 trial, adult PSC patients with ALP >1.5 × upper limit of normal (ULN) were randomized 2:1 to 1500 mg NCA once daily or to PBO. Randomization was stratified by concomitant ursodeoxycholic
acid (UDCA) use. Overall treatment duration is 192 weeks, with analysis of the primary endpoint at 96 weeks, followed by an ongoing 96-week DB extension phase. The combined primary endpoint at week 96 was partial normalization of ALP to <1.5 × ULN without worsening of fibrosis stage by Ludwig staging at week 96 compared to baseline in the full analysis set (FAS). Here, we report the results of the primary analysis after 96 weeks.
Results: A total of 301 patients were included in the FAS population (NCA: 205; PBO: 96 patients), with 213 (70.8%) completing to week 96. Baseline data were similar between treatment groups, with slightly more severe disease in the NCA group (Ludwig stage 3-4:
50.5% (NCA) vs. 37.9% (PBO); modified Nakanuma stage 3-4: 72.1% (NCA) vs. 55.8% (PBO); median ALP: 320 U/L (NCA) vs. 290 U/L (PBO)).
Concomitant UDCA use was reported for 78.7% of patients. At week 96, the percentage of patients achieving the primary endpoint was 15.1% for NCA versus 4.2% for PBO (p = 0.0048). Among patients without concomitant UDCA, significantly more reached the primary endpoint with NCA versus none with placebo (23.4% vs. 0.0%, n = 47 vs. n = 18; p = 0.0267). Improvement by at least 1 Ludwig stage was observed for 25.2% of NCA patients versus 10.5% in the PBO group (p = 0.0217). Conversely, only 20.3% of NCA patients worsened by at
least 1 Ludwig stage compared with 40.4% in the PBO group (p =0.0069). The percentage of patients with partial normalization of ALP without worsening of modified Nakanuma stage was 15.1% for NCA vs. 5.2% for PBO (p = 0.0086), confirming the superiority of NCA by a second histological score. Sustained biochemical improvement in the levels of multiple liver enzymes was observed with NCA but not PBO.
The study drug was well tolerated, with similar rates of patients with serious adverse events between both treatment groups.
Conclusion: In this pivotal phase 3 trial in adult patients with PSC, treatment with 1500 mg/day NCA for 96 weeks was safe and superior to placebo for the primary combined endpoint, indicating beneficial effects of NCA for halting disease progression.
It does seem to have similarities to the anecdotal evidence for Vanco. It should be noted that the NCA group were more advanced in progression versus the placebo. Perhaps, for people earlier in the disease progression, or those not responding to vanco, this might be worthwhile. My son was diagnosed in 2016, started Vanco in 2017 and immediately normalized with no progression found in MRI’s over the following years. However, since taking the 1st Covid booster, his bloodwork has gone back up and failed to normalize. Recent MRI’s and biopsy have shown progression (although he has never had a single symptom). Due to insurance, we have had to change doctors and his current doctor is only willing to continue the existing 1500 mg/day dose of Vanco. He will not consider increasing to 2000 mg. I’m quite frustrated by this.
It is great to have another option available (even 15% success rate is better than nothing).
Still no update when this would be approved and made available.
EASL conference had other promising results as well based on phase 2 trials showing similar efficacy (i.e. 15-17% achieved the primary endpoint). But phase 3 trials still take years.
So for the next 2-3 years, Vanco is the only option available (other than NCA Open label trial in Europe: ClinicalTrials.gov).