At the 2026 EASL Congress, a growing body of evidence suggested that the effectiveness of PBC treatment with PPAR agonists was consistent with that reported in phase III studies. Hear about the implications of these and other recent data from expert faculty Maria Londoño, MD, PhD.
With this podcast, featuring audio from a Medical Minute webcast, expert faculty Maria Londoño, MD, PhD, discusses how recent clinical trial and real-world data can improve treatment plans for patients with PBC. Listen now and visit the program page to download the accompanying slides.
Topics covered include:
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Presenters:
Maria Londoño, MD, PhD
Consultant Hepatologist
Hospital Clinic Barcelona
Associate Professor
University of Barcelona
Barcelona, Spain
This transcript was automatically generated from the audio recording and may contain inaccuracies, including errors or typographical mistakes.
Next Up in PBC Podcast: Updates From EASL 2026
[00:00:00] Hello, and welcome to Decera Clinical Education's Infectious Diseases podcast. I'm your host, Dr. Karen Straube West. Today's episode features audio from a medical minute webcast and explores how recent clinical trial and real world data can improve treatment plans for patients with PBC. In today's episode, I'm joined by Maria Londoño, MD, PhD. To view the full educational program and to download the accompanying slides, please visit the show notes for this episode. Now let's get started with Dr. Londoño.
Hello. My name is Maria Londoño. I am a hepatologist at Hospital Clinic in Barcelona, and today I will be, sharing with you the latest development for the PBC management that were presented at the last EASL meeting in May here in Barcelona So the presentation will be divided in three parts.
First, we are going to discuss a little bit on the real [00:01:00] world evidence for the new PPAR agonist. In the second part, I will be discussing some of the data in patients who were previously treated with second line therapies. And then at the end, I will comment on the patients who had an alkaline phosphatase between one and one point sixty-seven.
So let's start with the first part showing data on real world evidence for the new PPAR agonist. So in this study I will show you some data from the National Electronic Health Records in the US. This is a retrospective study analyzing patients with PBC with an alkaline phosphatase higher than one point sixty-seven, who received seladelpar after the approval by the FDA.
The pri- primary endpoint of this study was biochemical response defined by Boise criteria that you can see here in the slide. Means that the patient with response have an alkaline phosphatase lower than one [00:02:00] point sixty-seven, the upper limit of normal, plus a reduction of more than fifteen percent in the alkaline phosphatase as compared to baseline, and a total bilirubin lower than one point one time upper limit of normality.
And the key secondary endpoints was ALP normalization. And then at the end, uh, they also wanted to check on, side effects of the treatment. The cohort is divided in three groups. They are represented patients with PBC alone, patients with PBC and AIH variant that are so-called overlap patients, and then patients with PBC and MASLD.
Almost seventy percent of the patients with PBC achieve biochemical response, forty-eight percent of patients with PBC AIH variant, and finally, sixty-four percent of the patients with PBC and MASLD. In terms of ALP normalization, almost fifty percent of the patients with PBC achieve ALP normalization.
And then at the end, they also wanted to show the data according to the cirrhosis [00:03:00] status. In patients with cirrhosis had a significantly lower, uh, response rate as compared to patients without cirrhosis, fifty-five versus sixty-eight percent. We also had data on elafibranor.
These are the interim analysis of the ELAFINITY trial. This is a prospective phase four multi-center study in patients with PBC receiving e- elafibranor. In first, report, they show the data for the first fifty patients enrolled with month three outcomes. Fifty-p- four percent of the patients already achieved biochemical response after three months of the therapy.
And when they analyze the percentage of patients a- achieving ALP normalization, in the whole cohort, twenty-two percent of these patients achieve ALP normalization. And when they analyze only patients with an alkaline phosphatase between one and one point sixty-seven, forty percent of them already achieve ALP normalization after three months of the therapy.
[00:04:00] Both the whole cohort or patients who had previously received oveticolic acid, most of the patients present improvement or no change in alkaline phosphatase levels, and only a very small number of patients present worsening of ALP levels after the initiation of, uh, elafibranor.
And finally, they also wanted to show us the data or the impact of the therapy on symptoms. More than fifty percent of the patients present an improvement on fatigue, and almost all patients present an improvement in pruritus. But this data need to be analyzed carefully because the number of patients with moderate to severe pruritus in this interim analysis still very, very small So in summary from this, uh, first part, we can say that in real-world practice, PPAR agonists were associated with an increased rate of ALP normalization and higher rate of biochemical response.
So the second [00:05:00] part of this, uh, presentation will, focus on patients who were previously treated with another second-line therapy, either obeticholic acid or bezafibrate, and these are the most difficult to treat populations, and we are very excited to see what is going to happen in the, in the real-world data when we switch these patients from OCA or bezafibrate to the new PPAR agonist.
So this, first study is, um, a real-world evidence from the Italian early access program for elafibranor. This is a retrospective and prospective multicenter study in patients with PBC who discontinue obeticholic acid after the revocation of the commercialization in Europe. The primary endpoint of this analysis was the change in the median levels of alkaline phosphatase from baseline, and the key secondary endpoints were the proportion of patients achieving an alkaline phosphatase lower than one point sixty-seven, the upper limit of normal, or completely, uh, [00:06:00] normalization of alkaline phosphatase levels.
They also wanted to analyze the change in pruritus.
There was a reduction in the median levels of alkaline phosphatase , from one point sixty-nine times the upper limit of normality to a median levels of one point fourteen at the last, uh, elafibranor, exam.
And also, we can say that proportion of patients achieve levels of alkaline phosphatase lower than one point sixty-seven, sixty percent after twenty-four weeks of the therapy, and one-third of the study population achieve complete normalization of alkaline phosphatase after six months on therapy with elafibranor.
And also, in patients who had severe pruritus, uh, there was a significant improvement in, in the symptom of at least one point, and the median improvement in pruritus score was three point five points. And then we present da- data from Spain, from the COLLIDE registry here. W- I will show you [00:07:00] patients who receive seladelpar or elafibranor in real world practice here in Spain.
And the, uh, report is divided in, different groups. Patients who are naive to second-line therapy, one hundred and thirty-six. Patients previously treated with oveticolic acid in combination with UDC-8, one hundred and forty-seven. Patients previously treated with UDC-8 and besafibrate, eighty-two. And finally, a group of very difficult to treat patients, uh, who were receiving triple therapy with UDC-8, oveticolic acid, and besafibrate.
For patients who are naive to second-line therapy. The reduction of alkaline phosphatase is between thirty to forty percent already at after one month of the therapy, which is very similar to what has been reported , in the clinical trials.
Um, the proportion of patients achieving, biochemical response according to POIS criteria was eighty-nine percent for patients with elafibranor and sixty-eight for patients on seladelpar. But remember that the, the number of [00:08:00] patients achieving or reaching this, , time point is still small
In the patients who had already experienced treatment with obeticholic acid.
The reduction of alkaline phosphatase after one month of the therapy is around twenty to thirty percent, which is a little bit less than for naive, naive patients. But again, the proportion of patients reaching a biochemical response after six months of the therapy is very high, more than eighty percent.
And when we analyze patients who were receiving, uh, UDCA plus besafibrate, we can see that between forty to fifty percent of the patients achieve biochemical response after six months of the therapy. And finally in patients who were previously treated with triple therapy, UDCA, obeticholic acid, and besafibrate, the results are very different as compared to the previous groups.
Instead of a decrease in alkaline phosphatase levels, you can see an increase in the levels of alkaline phosphatase in both drugs, elafibranor [00:09:00] and seladelpar. And then at the end at six months, sixty-eight percent, uh, of patients remain on response according to POIS criteria for elafibranor, and f- forty-nine percent of patients receiving, uh, seladelpar remain on biochemical response according to POIS.
And finally, it's important to mention that a significant proportion of patients here, twenty-three percent and fifteen percent, lost the response according to Paris II or POIS criteria after discontinuation of the triple therapy. So in summary from this from this part of the presentation, we can say that after switching to elafibranor or seladelpar, we can say that the response rate in naive patients is still very high and similar to the, to that reported for the clinical trials.
And in patients who were previously treated with obeticholic acid or besafibrate, the response rate's still very good. But the problem is for patients who were receiving triple therapy, in which there was, , some loss of response after the [00:10:00] discontinuation of the, uh, obeticholic acid besafibrate.
So for the last part of the presentation, I will be focusing on patients who have alkaline phosphatase between one and one point six seven. So this is an important population because in the clinical trials that led to approval of both elafibranor or seladelpar they were only including patients with an alkaline phosphatase higher, higher than one point six seven.
And now we are providing new data showing that the response in patients with mildly elevated alkaline phosphatase are very, very good. So let's move now to the first, , study. So the first is it's, uh, a real world study in patients receiving elafibranor. So the data here is extracted again from electronic health record, data in the US called Health Verity, and the analysis focus only in patients who had alkaline phosphatase between one and one point [00:11:00] sixty-seven.
And the data is divided in two groups, in patients who were naive to second-line therapy and in patients who received another second-line therapy previous to the initiation of elafibranor. In both groups, previously treated or naive patients, there were significant decrease in ALP levels after six months of the therapy, with no significant changes in bilirubin levels And in terms of response, you can see here that patients naive to second-line therapy sixty percent of them achieve complete ALP normalisation, after six months of the therapy, and forty-six percent of patients who were previously experience or who have previously been treated with a second-line therapy achieve complete normalization of alkaline phosphatase.
And finally, we have some data from the ASSURE trial. Just to remind you, the ASSURE trial is an open label extension of the RESPONSE trial, which is [00:12:00] the phase three clinical trial f- that led to approval of seladelpar. And in this, open label extension, patients in the RESPONSE trial can start this open label phase.
And also there were patients from other seladelpar legacy studies that were able to participate in the ASSURE trial. And this specific analysis focus again in patients with mildly elevated levels of alkaline phosphatase between one and one point sixty-seven. A significant proportion of patients achieve complete normalization of alkaline phosphatase, which is at seventy-six percent after twenty-four months of the therapy, and a significant number of patients achieve a more, more than fifteen percent reduction in alkaline phosphatase, again, at twenty-four months of the therapy, eight- eighty-five percent.
And then again, from the ASSURE trial, there is important data analyzing the impact of response on, uh, [00:13:00] liver stiffness measurement. Patients who achieve complete biochemical response defined by BOIS criteria the liver stiffness measurement is stabilizing or even improving a little bit after thirty-six months of the therapy.
And on the contrary patients who did not achieve a biochemical response present an increase in liver stiffness measurement during the follow-up They did some univariate analysis and, and found that old age, low levels of alkaline phosphatase, and complete biochemical response were associated with improvement in liver stiffness measurement.
And in the multivariate analysis, the only variable that was independently associated with changes in FibroScan was the achievement of biochemical response. And then the impact of biochemical response in the changes on FibroScan.
The odds ratio favors all the time biochemical response. So [00:14:00] patients who achieve biochemical response, either complete normalization of alkaline phosphatase or biochemical response according to Paris criteria, show an improvement or a stabilization of fa- of liver stiffness measurement during the follow-up.
And then, uh, in summary from this last part , of the presentation, we can say that in patients with mildly elevated alkaline phosphatase between one and 1.67 the upper limit of normality, PPI agonists were associated with high rates of biochemical response and ALP normalization. And the as- in the ASSURE, ASSURE Trial, biochemical response is also associated with a stabilization or improvement in liver stiffness measurement.
Thank you very much for joining this program today, and I hope you like it. Thank you.
Thank you, Maria, and many thanks to you, our listeners, for joining us. To view the full program and download the accompanying slides, please click the link in the show notes. To get access to all of our new [00:15:00] podcasts, subscribe to the Deseret Clinical Education Podcast on Apple Podcasts, Google Podcasts, or Spotify.
Thank you and have a great day