Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication LIVDELZI is indicated for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who have had an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA. This indication is approved under accelerated approval based on a reduction of alkaline phosphatase (ALP) [see Clinical Studies (14) ] . FDA label
Also known as seladelpar 5, Livdelzi®, MBX-8025
Seladelpar · 11 trials · 6 indications
EFS is defined as measured by the time from start of treatment to the first occurrence of any of the following clinical events: 1. Death by any cause 2. Liver transplantation 3. MELD score ≥15 4. Ascites requiring treatment 5. Hospitalization for any of the following 1. Esophageal or gastric variceal bleeding 2. Hepatic encephalopathy 3. Spontaneous bacterial peritonitis
Percentages were rounded-off.
Percentages were rounded-off.
Treatment-emergent graded laboratory abnormalities were defined as values that increase at least 2 toxicity grade from baseline at any time post baseline. The laboratory abnormalities were graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), where Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: potentially life-threatening laboratory abnormality. The data is reported for shift of ≥ 2 grades from baseline in values for hematology and select liver biochemistry. Hematology includes parameters like RBCs, (erythrocytes), hemoglobin, hematocrit, platelets, WBC, WBC differentials (absolute and percentage) including basophils, neutrophils, lymphocytes, eosinophils, and monocytes, etc. Biochemistry included select liver function tests like blood bilirubin, gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase. Percentages were rounded-off.
Percentage of Participants with Response to Composite Endpoint of ALP \<1.67 × Upper Limit of Normal \[ULN\], ≥15% reduction in ALP, and total bilirubin ≤ ULN) at Month 3. The mITT analysis set included all randomized subjects who received at least one study drug dose. The primary endpoint was analyzed using Cochran-Mantel-Haenszel (CMH) test adjusted for both randomization stratification variables (ALP level: \<350 U/L and 2:350 U/L; pruritus NRS: \<4 and 2:4). The CMH tests were performed for the comparison of 10 mg versus placebo and 5 mg/10 mg versus placebo separately.
Relative change from baseline in serum ALP levels at Week 8 (endpoint). The modified Intent-to-Treat (mITT) analysis set included all randomized subjects with confirmed PBC who received at least one study drug dose and had at least one post baseline ALP evaluation on treatment. n, denotes number of subjects evaluable for the respective timepoints
Absolute and percentage (%) reduction in serum LDL-C at any point from baseline through Week 16.
Cmax is defined as the maximum observed plasma concentration of the study drug.
Tmax is defined as the time to reach the maximum observed plasma concentration of the study drug.
AUC0-t is defined as area under the concentration--time curve from time zero to the last measurable concentration.
AUC0-inf is defined as area under the concentration--time curve from time zero extrapolated to infinity, calculated as AUC0-t+Ct/Kel, where: Ct = the last measurable concentration and Kel = elimination rate constant.
Cmax is defined as the maximum observed plasma concentration of the study drug.
Cmax,ss is defined as the steady-state maximum observed plasma concentration of the study drug at Day 28.
Tmax is defined as the time to reach the maximum observed plasma concentration of the study drug.
Tmax,ss is defined as the steady-state time to reach maximum observed plasma concentration of the study drug at Day 28.
AUC0-24 is defined as area under the concentration-time curve from time zero to 24 hours.
AUCtau is defined as the area under the drug concentration versus time curve over the dosing interval.
RCmax is defined as the accumulation ratio based on Cmax, calculated as Cmax on Day 28/ Day 1.
RAUC0-t is defined as the accumulation ratio based on AUC0-t, calculated as AUC0-tau on Day 28/ AUC0-24 on Day 1 for participants with dose once a day.
An adverse event (AE) was defined as any medical occurrence in a participant administered to a pharmaceutical product in a clinical study, regardless of a causal relationship with this treatment. TEAEs were defined as AEs that commenced or worsened on or after the time of study drug administration in Part A until up to 30 days after study drug administration in Part A or before the first study drug administration in Part B (whichever is earlier). For Part B, TEAEs are defined as AEs that commence or worsen on or after the time of first study drug administration in Part B until up to 30 days after the last study drug administration in Part B. A drug-related TEAE was defined as TEAE which was related (reported as 'possible', 'probable', or 'definite') to study drug. Percentages were rounded off.
TEAEs severity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Fatal. Participants were counted at the highest AE grade experienced. The percentage of participants with any severity grade and severity grade of 3 or 4 were reported. Percentages were rounded off.
TEAEs of special interest for this study were defined as AEs that met CTCAE version 5.0 or the most recent version Grade 2 criteria or higher for AEs of elevated alanine transaminase (ALT), aspartate aminotransferase (AST), bilirubin, creatinine kinase, lipase, or serum creatinine. Hepatic decompensation clinical events including ascites, jaundice, esophageal variceal bleeding, and hepatic encephalopathy, were also defined as TEAEs of special interest for this study. Percentages were rounded off.
Vital signs (including oral temperature, respiratory rate, seated blood pressure \[diastolic and systolic\], and heart rate) were evaluated. Percentage of participants with clinically significant changes in vital signs evaluations was reported. The clinically significant changes were based on investigator's judgement.
ECG measurements included the parameters of heart rate, ventricular rate, PR interval, QRS duration, QT interval (uncorrected), and QT interval corrected for heart rate according to Fridericia's formula (QTcF). Per protocol, ECG findings were classified in 1 of 3 categories: normal, abnormal but not clinically significant, or abnormal and clinically significant. Any abnormality in ECG assessments which were deemed clinically significant by the investigator were reported.
Clinical laboratory parameters included biochemistry, hematology, coagulation, and urinalysis. Abnormal laboratory values were graded according to the NCI CTCAE version 5.0.Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Fatal. The percentage of participants with a shift of ≥ 2 NCI CTCAE grade from baseline was reported.
| Arm | Type | Description |
|---|---|---|
| Seladelpar | EXPERIMENTAL | Participants with Child-Pugh (CP)-A cirrhosis will receive seladelpar 10 mg orally once daily or participants with CP-B cirrhosis will receive seladelpar 5 mg orally once daily, for up to 36 months. |
| Placebo | PLACEBO_COMPARATOR | Participants with CP-A or CP-B will be randomized to received placebo to match one capsule daily for up to 36 months. |
| Open Label Extension Phase | EXPERIMENTAL | Participants with CP-A who remained on the study drug at week 156 will receive seladelpar 10 mg daily or participants with CP-B will received seladelpar 5 mg daily for a maximum of 3 years. |
| Seladelpar 5-10 mg | EXPERIMENTAL | - |
| Seladelpar 10 mg | EXPERIMENTAL | - |
| Seladelpar 5 mg Capsules | EXPERIMENTAL | - |
| Seladelpar 10 mg Capsule | EXPERIMENTAL | - |
| Seladelpar (SEL) 10 mg + Placebo-to-Match (PTM) Cilofexor (CILO) Dose A + CILO Dose B | EXPERIMENTAL | Participants will receive a dose of SEL 10 mg capsule along with PTM CILO Dose A tablets and CILO Dose B tablets, once daily up to 24 weeks. At completion of Week 24, participants will continue in an Active Treatment Extension (ATE) Period, during which they will receive SEL 10 mg along with either CILO Dose A or Dose B at the original randomized dose in a blinded fashion, up to Week 312. |
| SEL 10 mg + CILO Dose A + PTM CILO Dose B | EXPERIMENTAL | Participants will receive a dose of SEL 10 mg capsule along with CILO Dose A tablets and PTM CILO Dose B tablets, once daily up to 24 weeks. At completion of Week 24, participants will continue in an ATE Period, during which they will receive SEL 10 mg along with either CILO Dose A or Dose B at the original randomized dose in a blinded fashion, up to Week 312. |
| SEL 10 mg + PTM CILO Dose A + PTM CILO Dose B | ACTIVE_COMPARATOR | Participants will receive a dose of SEL 10 mg capsule along with PTM CILO Dose A tablets and PTM CILO Dose B tablets, once daily up to 24 weeks. At completion of Week 24, participants will continue in an ATE Period, during which they will initiate open-label SEL 10 mg and be re-randomized in a 1:1 ratio to receive CILO Dose A or Dose B in a blinded fashion, up to Week 312. |
| PTM SEL 10 mg + PTM CILO Dose A + PTM CILO Dose B | PLACEBO_COMPARATOR | Participants will receive a dose of PTM SEL 10 mg capsule along with PTM CILO Dose A tablets and PTM CILO Dose B tablets once daily up to 24 weeks. At completion of Week 24, participants will continue in an ATE Period, during which they will initiate open-label SEL 10 mg and be re-randomized in a 1:1 ratio to receive CILO Dose A or Dose B in a blinded fashion, up to Week 312. |
| MBX-8025 (2 mg) | EXPERIMENTAL | MBX-8025 2 mg capsule once daily |
| MBX-8025 (5 mg) | EXPERIMENTAL | MBX-8025 5 mg capsule once daily |
| MBX-8025 (10 mg) | EXPERIMENTAL | MBX-8025 10 mg capsule once daily |
| placebo, MBX-8025 50 mg, 100 mg or 200 mg capsules | EXPERIMENTAL | - |
| Placebo/Placebo | PLACEBO_COMPARATOR | - |
| MBX-8025 50 mg/Placebo | EXPERIMENTAL | - |
| MBX-8025 100 mg/Placebo | EXPERIMENTAL | - |
| Placebo/Atorvastatin 20 mg | ACTIVE_COMPARATOR | - |
| MBX-8025 50 mg/Atorvastatin 20 mg | EXPERIMENTAL | - |
| MBX-8025 100 mg/Atorvastatin 20 mg | EXPERIMENTAL | - |
| Part A: Cohort 1 - CP-A Without PHT (Seladelpar 10 mg) | EXPERIMENTAL | Participants with primary biliary cholangitis (PBC) and a Child-Pugh (CP) classification of CP-A (score 5 to 6) without portal hypertension (PHT) will receive a single dose of seladelpar 10 mg, orally, on Day 1. |
| Part A: Cohort 2 - CP-A With PHT (Seladelpar 10 mg) | EXPERIMENTAL | Participants with PBC and a CP classification of CP-A (score 5 to 6) with PHT will receive a single dose of seladelpar 10 mg, orally, on Day 1. |
| Part A: Cohort 3 - CP-B (Seladelpar 10 mg) | EXPERIMENTAL | Participants with PBC and a CP classification of CP-B (score 7 to 9) will receive a single dose of seladelpar 10 mg, orally, on Day 1. |
| Part A: Cohort 4 - CP-C (Seladelpar 10 mg) | EXPERIMENTAL | Participants with PBC and a CP classification of CP-C (score 10 to 12) will receive a single dose of seladelpar 10 mg, orally, on Day 1. |
| Experimental: Part B: Cohort 2 - CP-A With PHT (Seladelpar 5 mg or 10 mg) | EXPERIMENTAL | Participants with PBC and a CP classification of CP-A (score 5 to 6) with PHT, who complete Part A, will receive seladelpar 10 mg or 5 mg, orally, once daily, for 28 days. Doses for Part B will be chosen based on exposure from a single dose in Part A for individual participants. |
| Experimental: Part B: Cohort 3 - CP-B (Seladelpar 5 mg or 10 mg) | EXPERIMENTAL | Participants with PBC and a CP classification of CP-B (score 7 to 9), who complete Part A, will receive seladelpar 10 mg or 5 mg, orally, once daily, for 28 days. Doses for Part B will be chosen based on exposure from a single dose in Part A for individual participants. |
| Normal | EXPERIMENTAL | Child-Pugh Score: N/A Subjects will receive a single 10 mg oral dose of seladelpar |
| Mild Impairment | EXPERIMENTAL | Child-Pugh Score: A (5 to 6 points) Subjects will receive a single 10 mg oral dose of seladelpar |
| Moderate Impairment | EXPERIMENTAL | Child-Pugh Score: B (7 to 9 points) Subjects will receive a single 10 mg oral dose of seladelpar |
| Severe Impairment | EXPERIMENTAL | Child-Pugh Score: C (10 to 15 points) Subjects will receive a single 10 mg oral dose of seladelpar |
| Name | Type | Description |
|---|---|---|
| Seladelpar | DRUG | Administered orally |
| Placebo | DRUG | Administered orally |
| Seladelpar 10 mg | DRUG | Administered orally |
| Seladelpar 5 mg | DRUG | If down-titration needed, one capsule daily for double-blind period, for a duration of up to 12 months |
| seladelpar 5-10 mg | DRUG | Seladelpar 5 mg for 6 months and then titrating up to 10 mg based on tolerability and response for remainder of double-blind period. After completion of the 1-year double-blind period subjects will be offered the opportunity to enter an open label long term safety study. Subjects will continue the seladelpar dose (5 or 10 mg) received during the double-blinded study |
| Seladelpar 5 mg Capsule | DRUG | Participants will be assigned to a treatment group if tolerability issues noted in the previous study. |
| Seladelpar 10 mg Capsule | DRUG | Participants will be assigned to a treatment group unless there are tolerability issues. |
| PTM Seladelpar | DRUG | Capsule administered orally |
| Cilofexor Dose B | DRUG | Tablet administered orally |
| PTM Cilofexor Dose A | DRUG | Tablet administered orally |
| PTM Cilofexor Dose B | DRUG | Tablet administered orally |
| Cilofexor Dose A | DRUG | Tablet administered orally |
| MBX-8025 2 mg Capsule | DRUG | Initial 8-week treatment: • MBX-8025 2 mg Extension: The 2 mg group will be started after safety and efficacy review of the 5 mg and the 10 mg groups has been completed. Subjects will initially enter the extension on their assigned dose. The dose might be up- or down-titrated after safety and efficacy data review of the first 8 weeks of treatment. During the extension, a subject's dose might be re-adjusted for safety or efficacy reasons. |
| MBX-8025 5 mg Capsule | DRUG | Initial 8-week treatment: • MBX-8025 5 mg Extension: Subjects will initially enter the extension on their assigned dose. The dose might be up- or down-titrated after safety and efficacy data review of the first 8 weeks of treatment. During the extension, a subject's dose might be re-adjusted for safety or efficacy reasons. |
| MBX-8025 10 mg Capsule | DRUG | Initial 8-week treatment: • MBX-8025 10 mg Extension: Subjects will initially enter the extension on their assigned dose. The dose might be up- or down-titrated after safety and efficacy data review of the first 8 weeks of treatment. During the extension, a subject's dose might be re-adjusted for safety or efficacy reasons. |
| Run-In Period: Placebo | OTHER | 2 capsules, once a day for two weeks |
| MBX-8025 50 mg (Dose Escalation Period 1) | DRUG | 1 capsule once a day for 4 weeks (MBX-8025 50 mg capsule) |
| MBX-8025 50 mg or 100 mg (Dose Escalation Period 2) | DRUG | 1 capsule once a day for 4 weeks (MBX-8025 50 mg or 100 mg capsule) |
| MBX-8025 50 mg, 100 mg or 200 mg (Dose Escalation Period 3) | DRUG | 1 or 2 capsules once a day for 4 weeks (MBX-8025 50 mg, 100 mg or two (2) 100 mg capsules) |
| MBX-8025 | DRUG | 2 capsules, once daily for 8 weeks |
| Atorvastatin | DRUG | 2 capsules, once daily for 8 weeks |
Inclusion Criteria: Individuals must meet the following criteria to be eligible for study participation: 1. Must be at least 18 years old. 2. Must have a confirmed prior diagnosis of primary biliary cholangitis (PBC) 3. Evidence of cirrhosis 4. CP Score A or B 5. Females of reproductive potential ...
Seladelpar is an investigational small molecule developed by Gilead Sciences, Inc. (ticker GILD) for gastrointestinal and liver conditions. It is being studied in primary biliary cholangitis, also called primary biliary cirrhosis, and in hepatic impairment. It is not yet approved and remains in clinical development across Phase 1, Phase 2, and Phase 3 studies.
Seladelpar targets PPARD, also known as peroxisome proliferator-activated receptor delta. It acts as an agonist at this target, meaning it activates the receptor. PPARD agonism is the mechanism under investigation for its effects in primary biliary cholangitis and related liver conditions.
Seladelpar is being developed for primary biliary cholangitis, a chronic liver disease also referred to as primary biliary cirrhosis. Clinical studies have evaluated it in patients with PBC, including those with compensated cirrhosis, and have assessed its effects on alkaline phosphatase levels. It is investigational and has not been approved for this use.
Seladelpar is developed by Gilead Sciences, Inc., which trades under the ticker GILD. Gilead is the sponsor of the clinical program studying seladelpar in primary biliary cholangitis and hepatic impairment.
Seladelpar has been studied across Phase 1, Phase 2, and Phase 3 clinical trials. Six trials are recorded in total, of which two are active and four are completed, with combined enrollment of 1,112 participants. Seladelpar is investigational and is not approved.
Seladelpar trials include NCT06051617, a recruiting Phase 3 study in PBC with compensated cirrhosis, and NCT07841977, a Phase 2 study of seladelpar and cilofexor in PBC that is not yet recruiting. Completed studies include the Phase 3 NCT06060665 and the Phase 1 NCT04950764 in PBC with hepatic impairment.