{
  "abstract": "Introduction Seladelpar (SEL) is a first-in-class delpar (selective PPAR-delta agonist) indicated for the treatment of primary biliary cholangitis (PBC), including pruritus, in adults in combination with ursodeoxycholic acid (UDCA) who have an inadequate response to UDCA alone, or as monotherapy in those unable to tolerate UDCA. Here, we report the latest interim, long-term biochemical efficacy and safety data in a pooled population of patients (pts) treated with SEL in ASSURE.Methods The ASSURE study ( NCT03301506) is an ongoing, open-label, long-term, Phase 3 trial of SEL in pts with PBC rolling over from the placebo-controlled, Phase 3 RESPONSE trial (NCT04620733) or with prior participation in legacy SEL trials. Phase 2 and 3 parent studies for ASSURE required inadequate response or intolerance to UDCA. Using a data cutoff of 31-Jan-2025, pts were pooled starting with their initiation of SEL (at entry into RESPONSE for those randomised to SEL, entry into ASSURE for all other pts). Pts received blinded, daily oral SEL 10 mg in RESPONSE and open-label, daily oral SEL 10 mg in ASSURE. Efficacy endpoints included a composite biochemical response (CBR; ALP <1.67 × the upper limit of normal [ULN], ALP decrease ≥15% from baseline [BL], and total bilirubin ≤ULN), ALP normalisation, ALP % change from BL, and other laboratory parameters summarised through 36 months (M). Safety was assessed by exposure-adjusted adverse events (AEs) per 100 pt-years (yrs) of exposure through 48M.Results Among 337 pts treated with open-label SEL 10 mg, 258 were treated for ≥2 yrs and 117 were treated for ≥3 yrs, with 122 pts reaching their 36M visit as of the data cutoff. The majority of pts achieved a CBR: 69% (225/325) at 12M, 70% (181/258) at 24M, and 67% (82/122) at 36M ( figure 1A). ALP normalised in 35% of pts (114/325) who reached their 12M visit, similarly, of 37% (96/258) at 24M and 34% (41/122) at 36M (figure 1B). Treatment with SEL resulted in sustained reductions in ALP, with mean % changes from BL of −43% at 12M, −43% at 24M, and −40% at 36M (figure 1C). Sustained reductions were also observed in ALT and GGT through 36M. SEL was well tolerated, with overall AEs reported in 83.2 pts per 100 pt-yrs in yr 1 and 62.3 in yr 4.Conclusions SEL led to sustained reductions in biochemical markers of cholestasis with up to 36M of open-label treatment. SEL also appeared to be safe and well tolerated; no new safety signals were identified with up to 48M of follow up.Abstract P62 Figure 1Composite biochemical response (A), ALP normalisation (B), ALP % change from BL (C) through 36 months of open-label seladelpar treatmentn/N = number of responders at each time point/total number of evaluable patients at each time point.n = number of evaluable patients at each time point.ALP, alkaline phosphatase; BL, baseline; CI, confidence interval; SE, standard error",
  "authors": [
    {
      "affiliations": [
        "Gilead Sciences, Inc., Foster City, USA"
      ],
      "name": "Arran Ludlow-Rhodes"
    },
    {
      "affiliations": [
        "Texas Liver Institute, University of Texas Health San Antonio, San Antonio, USA"
      ],
      "name": "Eric Lawitz"
    },
    {
      "affiliations": [
        "Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento, USA"
      ],
      "name": "Christopher Bowlus"
    },
    {
      "affiliations": [
        "Gilead Sciences, Inc., Foster City, USA"
      ],
      "name": "Kyung Min Kwon"
    },
    {
      "affiliations": [
        "Gilead Sciences, Inc., Foster City, USA"
      ],
      "name": "Sarah Proehl"
    },
    {
      "affiliations": [
        "Gilead Sciences, Inc., Foster City, USA"
      ],
      "name": "Xin Qi"
    },
    {
      "affiliations": [
        "Gilead Sciences, Inc., Foster City, USA"
      ],
      "name": "Robert Kustra"
    },
    {
      "affiliations": [
        "The Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina"
      ],
      "name": "Alejandra Villamil"
    },
    {
      "affiliations": [
        "Autoimmune and Cholestatic Liver Center, Massachusetts General Hospital, Boston, USA,"
      ],
      "name": "Daniel Pratt"
    }
  ],
  "title": "P62 Seladelpar linked to sustained reduction in cholestatic markers with consistent safety profile in PBC up to 48 months in ASSURE",
  "uid": "42f9ddbf-1545-5699-a0c8-d06ac6a36748"
}