OP-1 LONG-TERM EFFICACY AND SAFETY OF OPEN-LABEL SELADELPAR TREATMENT IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS: INTERIM 2-YEAR RESULTS FROM THE ASSURE STUDY
Bibliographic record
Abstract
Conflict of interest: Yes, Full disclosures sent separately. Introduction and Objectives: Seladelpar reduces biochemical markers of cholestasis and pruritus in patients with primary biliary cholangitis. ASSURE (NCT03301506) is an ongoing, open-label, long-term Phase 3 trial of seladelpar in patients rolling over from Phase 3 RESPONSE (NCT04620733) or legacy studies (NCT03602560, NCT02955602, NCT03301506, and NCT04950764). We report interim 2-year efficacy and safety results. Patients / Materials and Methods: Patients with insufficient response/intolerance to ursodeoxycholic acid could enroll in ASSURE. Key endpoints were composite biochemical response (alkaline phosphatase [ALP] <1.67 × upper limit of normal [ULN], ALP decrease ≥15%, and total bilirubin ≤ULN) and ALP normalization. Pruritus was measured using numerical rating scale (NRS; 0–10). For patients enrolling from RESPONSE, baseline was entry to RESPONSE and analyzed as continuous seladelpar or crossover from placebo; legacy patients were analyzed separately with baseline defined as entry to ASSURE. Results and Discussion: As of 01/2024, 158 RESPONSE and 179 legacy patients received seladelpar 10 mg daily for up to 155 weeks. In RESPONSE, 61.7% of patients met the endpoint at 12 months (M) vs 20% for placebo. In ASSURE, 61.8% (6M) and 72.4% (12M) met the composite endpoint; 75% (6M) and 93.8% (12M) of placebo crossover patients met the endpoint. In RESPONSE, ALP normalized in 25% of seladelpar and 0 placebo patients at 12M. With continued treatment, 33.3% (6M) and 17.2% (12M) had ALP normalization; 26.9% (6M) and 50% (12M) of crossover patients had ALP normalization. In ASSURE, 6-month change from baseline in pruritus NRS was similar to RESPONSE: −3.8 and −3.7 in continuous and crossover patients, respectively. At 12M and 24M, 73.2% and 69.7% of legacy patients met the endpoint in ASSURE; 42.1% and 42.4% achieved ALP normalization, and reduction in pruritus NRS was −3.8 and −3.1, respectively. There were no treatment-related serious adverse events. Conclusions: Seladelpar treatment led to improvements in biochemical markers and pruritus, and was well tolerated with long-term use.
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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 | 0.004 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.007 | 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".