WASHINGTON, DC — Measures of liver stiffness remained stable or improved in patients with primary biliary cholangitis (PBC) after 36 months of treatment with seladelpar (Livdelzi) based on new data from the ongoing ASSURE study. 

These interim results support the drug’s potential for long-term disease management by addressing a key marker of disease progression, said study author D. Barry Crittenden, MD, executive director of clinical development for seladelpar manufacturer, Gilead, in an interview.

“Patients with [PBC] who have advanced fibrosis or cirrhosis tend to show progressive increases in liver stiffness measurements (LSMs) over time, despite first-line treatment with ursodeoxycholic acid (UDCA),” lead author Christopher L. Bowlus, MD, from the University of California Davis School of Medicine, Sacramento, and his colleagues explained in their presentation here at The Liver Meeting 2025: American Association for the Study of Liver Diseases (AASLD). 

Liver stiffness is an important marker of PBC progression which remains underexplored, added Crittenden, noting that no head-to-head trials are currently available to compare investigational compounds in PBC.

Seladelpar is a selective peroxisome proliferator-activated receptor delta agonist indicated for the treatment of PBC in adults as an adjunct to first-line treatment with UDCA in patients with an inadequate response or as monotherapy for those unable to tolerate UDCA.

Extension of the RESPONSE Trial 

The open-label phase 3 ASSURE trial is an ongoing extension of the RESPONSE trial, a pivotal trial that examined the impact of seladelpar on the primary endpoint of biochemical response in PBC. In that trial, as reported by Medscape Medical News, 61.7% of patients treated with seladelpar met the primary endpoint vs 20% on placebo.

The ASSURE study enrolled 337 patients, from both the RESPONSE study and from other seladelpar legacy studies. 

Previous results from the ASSURE study showed that seladelpar was significantly associated with biochemical response, alkaline phosphatase normalization, and itching through 3 years compared to placebo, Crittenden told Medscape Medical News. However, its long-term impact on LSM had not been previously evaluated. 

The current analysis included 114 patients who had at least one post-baseline LSM and had received 10 mg of oral seladelpar once daily and had available data at 36 months. Liver stiffness was measured using vibration-controlled transient elastography. The mean age of the participants was 58 years, and 95% were female. 

Up to 85% of the participants showed stable or improved LSMs at 36 months. The overall median change in liver stiffness was -0.2 kPa (-3%). 

Notably, patients at the highest risk of PBC progression (defined as LSM of 16.9 kPa or higher at baseline) showed a trend towards improvement, with a median change of -5.2 kPa (-30%), the researchers said. 

Patients whose LSM worsened by 30% or more were generally younger and had higher baseline levels of alkaline phosphatase at baseline, although other characteristics were similar, the researchers noted.

Prognostic Value of Liver Stiffness Measurements

“There is growing interest in the use of serial LSMs to monitor and risk-stratify chronic liver disease patients,” wrote Yu Jun Wong, from the Division of Gastroenterology and Liver Unit, University of Alberta, Canada, and colleagues in a separate study published earlier this fall in the Journal of Hepatology.

This is “because this strategy might capture the impact of both the baseline risk of liver-related events and disease modifiers following the index LSM,” they explained. 

While both LSM and biochemical response have prognostic significance in PBC, discordance between measurements is frequent, the study authors noted. 

In an analysis of 1793 patients with PBC, they found that if the most recent LSM was greater than 10 kPa it strongly predicted liver-related events in PBC, irrespective of prior biochemical response or LSM trajectory.

However, they point out, “The present results do not contradict our previous data showing that the LSM trajectory in PBC has prognostic value independent of the baseline LSM. In the previous study, we showed that dynamic changes in LSM could be used, alongside with biochemical response, as a potential surrogate measure of disease outcome.”

The study was supported by Gilead. Crittenden is employed by Gilead. Multiple authors of the study by Wong et al declare relationships with different pharmaceutical companies including Gilead.