P47 Efficacy and safety of seladelpar as monotherapy in patients with primary biliary cholangitis and intolerance to ursodeoxycholic acid
Bibliographic record
Abstract
Seladelpar is a first-in-class delpar (selective PPAR-delta agonist) indicated in the UK for the treatment of primary biliary cholangitis (PBC) including pruritus in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA. In two Phase 3, placebo-controlled studies (ENHANCE [NCT03602560], RESPONSE [NCT04620733]), seladelpar led to a significantly higher rate of composite biochemical response (CBR; alkaline phosphatase [ALP] <1.67 × the upper limit of normal [ULN], ≥15% decrease in ALP, and total bilirubin [TB] ≤ULN) and ALP normalization compared with placebo. Here, we present pooled efficacy and safety data on patients with UDCA intolerance receiving seladelpar as monotherapy in these studies. Patients with PBC who had an inadequate response or intolerance to UDCA, ALP ≥1.67 × ULN, and TB ≤2 × ULN were randomized in 2 trials: ENHANCE (1:1:1 to daily placebo, seladelpar 5 mg, or seladelpar 10 mg for 52 weeks; study terminated early with endpoints amended to month 3) and RESPONSE (2:1 to daily seladelpar 10 mg or placebo for 52 weeks). Patients intolerant to UDCA were eligible if their last dose was >3 months before study entry. This post hoc analysis presents pooled efficacy (CBR, ALP normalization, and other liver biochemistries) and safety data for seladelpar 10 mg monotherapy vs placebo from ENHANCE and RESPONSE through month 3. In total, 369 patients were randomized to seladelpar 10 mg or placebo across both studies, 16 of whom received seladelpar monotherapy and 6 received placebo without UDCA. Mean baseline ALP was similar between monotherapy patients receiving seladelpar vs placebo (380 U/L vs 397 U/L). At month 3, 8/13 patients (62%) receiving seladelpar monotherapy demonstrated a CBR vs 1/6 patients (17%) receiving placebo, and 3/13 patients (23%) on seladelpar achieved normalized ALP vs 0/6 patients on placebo. Mean percent change from baseline in ALP at month 3 was −46% with seladelpar vs −2% with placebo. At month 3, 9/16 patients (56%) on seladelpar monotherapy experienced an adverse event (AE) vs 5/6 patients (83%) on placebo. No serious AEs and no discontinuations due to AEs occurred through month 3 with seladelpar monotherapy. Efficacy and safety results for seladelpar monotherapy were similar to results previously observed for seladelpar combined with UDCA. Seladelpar 10 mg monotherapy led to notable CBR rates and ALP reductions. Seladelpar monotherapy was well tolerated and had a similar safety profile compared with placebo.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".