Treatment with seladelpar for 4 years yields consistent biochemical efficacy, with no new safety concerns, among patients with cirrhosis and primary biliary cholangitis (PBC), as shown by interim results from the open-label ASSURE study.
“Seladelpar continues to demonstrate sustained biochemical efficacy and a favourable safety profile in cirrhosis patients with PBC, including [those] with features of portal hypertension, with up to 4 years of treatment,” said lead study author Dr Aliya Gulamhusein, Division of Gastroenterology and Hepatology, Toronto Centre for Liver Disease, University of Toronto, Toronto, Canada.
Gulamhusein and her team enrolled patients from RESPONSE and prior seladelpar studies in ASSURE and pooled those with cirrhosis per protocol at baseline, defined as seladelpar initiation in RESPONSE or ASSURE. Participants received seladelpar 10 mg once daily.
In post hoc analysis, patients with cirrhosis were identified as having features of portal hypertension if they met one or more of the following criteria at baseline: platelets <140 × 103/uL, low albumin, elevated total bilirubin (TB), ascites, or medical history of varices or portal hypertension.
Gulamhusein and colleagues assessed efficacy endpoints through month 36, including composite biochemical response (CBR; alkaline phosphatase [ALP] <1.67 x the upper limit of normal [ULN], ≥15- percent decrease in ALP, and TB ≤1.0 x ULN), ALP normalization, and other laboratory changes. They also examined the safety profile of seladelpar.
Of the 337 patients enrolled in the study, 53 (16 percent) had cirrhosis at baseline. Most were Child-Pugh (CP)-A, with four (8 percent) CP-B. Their mean ALP was 267.5 U/L, TB was 0.98 mg/dL, and liver stiffness was 20.6 kPa at baseline. More than half (n=29, 55 percent) of the participants presented with features of portal hypertension. [EASL 2026, abstract SAT-287]
At month 12, 25 of 51 patients (49 percent) achieved CBR, with a similar proportion achieving this endpoint at month 36 (9/19, 47 percent). The mean change in ALP from baseline was ‒35 percent at month 12 and ‒28 percent at month 36.
Furthermore, 15 of the 51 patients (29 percent) also achieved ALP normalization at month 12, and three of 19 (16 percent) with available data had normal ALP at month 36.
Safety
Almost all evaluable patients (50/53, 94 percent) reported adverse events (AEs). Four of them experienced events that met the criteria for a PBC clinical outcome, but none were assessed as related to seladelpar.
The most common AEs associated with seladelpar were headache (8 percent), abdominal pain (7 percent), nausea (6 percent), abdominal distension (6 percent), and dizziness (5 percent). A few of them (4 percent) also had fractures. [https://www.gilead.com/news/news-details/2026/phase-3-assure-interim-data-majority-of-people-in-the-study-with-alp-11-67uln-achieved-high-and-sustained-composite-alp-normalization-at-24-months-with-gileads-livdelzi-seladelpar]
The use of seladelpar had also been shown to result in dose-related increases in serum transaminase (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) levels >3 x ULN in patients receiving 50- and 200-mg doses once daily. However, transaminase levels returned to pretreatment levels following discontinuation.
None of the patients with abnormal AST or ALT at baseline experienced an AST or ALT ≥2 × baseline, according to Gulamhusein and her team.
“Seladelpar is a first-in-class delpar (selective PPAR-delta agonist) indicated for the treatment of PBC in combination with ursodeoxycholic acid (UDCA) in patients with an inadequate response to UDCA or as monotherapy in patients unable to tolerate UDCA,” said Gulamhusein and colleagues.
“In the pivotal RESPONSE study, seladelpar had similar efficacy in patients with or without compensated cirrhosis and safety generally similar to placebo,” they added.