62% of patients achieved biochemical response with LIVDELZI1
RESPONSE was a 12-month, randomized, double-blind phase 3 pivotal trial that assessed the efficacy and safety of LIVDELZI 10 mg ± UDCA (n=128) vs placebo ± UDCA (n=65), administered once daily.1
Statistically significant improvement across FDA-accepted markers of cholestasis vs placebo1-3
Composite biochemical response at 12 months1
Primary endpoint1: Composite biochemical response, defined as achieving the following at 12 months:
ALP <1.67 x ULN
≥15% decrease in ALP from baseline
TB ≤1 x ULN
ULN for ALP was defined as 116 U/L for females and males1,2
Composite biochemical response at 12 months1
Primary endpoint1: Composite biochemical response, defined as achieving the following at 12 months:
ALP <1.67 x ULN
≥15% decrease in ALP from baseline
TB ≤1 x ULN
ULN for ALP was defined as 116 U/L for females and males1,2
LIVDELZI monotherapy
Biochemical response at 3 months comparing LIVDELZI as a monotherapy with placebo was evaluated in a pooled analysis of a subset of patients from RESPONSE and another randomized, double-blind, placebo-controlled trial in a similar patient population. There was a trend of improvement on biochemical response at 3 months in the LIVDELZI monotherapy group compared with the placebo group.1*
*In the RESPONSE trial, 12 patients (6%) were intolerant to UDCA and initiated treatment as monotherapy: 8 patients (6%) in the LIVDELZI 10 mg arm and 4 patients (6%) in the placebo arm.1
Primary endpoint1
Composite biochemical response at 12 months:
ALP <1.67 x ULN
≥15% decrease in ALP from baseline
TB ≤1 x ULN
Key secondary endpoints1
ALP normalization at 12 months, defined as ALP ≤1.0 x ULN
Change from baseline in mean pruritus NRS score at 6 months was analyzed using a mixed-effect model for repeated measures§
Select secondary endpoint2
Mean change in ALP at 12 months
Inclusion criteria1,2
PBC with an inadequate response or intolerance to UDCA (on treatment ≥12 months; last dose >3 months prior to screening)
ALP <1.67 x ULN
TB ≤2 x ULN
ALT/AST ≤3 x ULN
Exclusion criteria1
Other chronic liver diseases
Clinically important hepatic decompensation
Portal hypertension with complications
Cirrhosis with complications (MELD score ≥12, known esophageal varices or variceal bleeds, history of hepatorenal syndrome)
After 12 months, patients from both arms of the RESPONSE trial could enroll in an open-label, long-term study2
†Patients were randomized in a 2:1 ratio.1
‡LIVDELZI or placebo was administered in combination with UDCA in 181 (94%) patients during the trial, or as a monotherapy in 12 (6%) patients who were unable to tolerate UDCA.1
§The pruritus NRS is a scale ranging from 0 (no itch) to 10 (worst itch imaginable).1
LIVDELZI was evaluated in a broad range of patients with PBC2,4
Select baseline demographics and characteristics1,2,4,5
Mean ± SD
Placebo ± UDCA n=65 (%)
LIVDELZI 10 mg ± UDCAn=128 (%)
Female, n (%)
60 (92.3)
123 (96.1)
Age, years
57.0 ± 9.2
56.6 ± 10.0
Duration of disease, years
8.6 ± 6.5
8.2 ± 6.7
Compensated cirrhosis, n (%)
9 (13.8)
18 (14.1)
14% compensated cirrhosis
14% compensated cirrhosis
On UDCA, n (%)
61 (93.8)
120 (93.8)
Pruritus NRS ≥4, n (%)
23 (35.4)
49 (38.3)
Hx of osteopenia, n (%)
8 (12.3)
17 (13.3)
13% or 14% history of osteopenia or osteoporosis
Hx of osteoporosis, n (%)
5 (7.7)
18 (14.1)
13% or 14% history of osteopenia or osteoporosis
Liver function values
ALP, U/LULN: 116 U/L
313.8 ± 117.7
314.6 ± 123.0
ALP ≥350 (3 x ULN), n (%)
18 (27.7)
35 (27.3)
ALP <350 U/L, n (%)
47 (72.3)
93 (72.7)
TB, mg/dLULN: 1.1 mg/dL
0.74 ± 0.3
0.77 ± 0.3
TB >1 x ULN & ≤2 x ULN, n (%)
5 (7.7)
20 (15.6)
ALT, U/LULN: 41 U/L
48.2 ± 22.8
47.4 ± 23.5
AST, U/LULN: 34 U/L
41.7 ± 16.0
39.6 ± 16.1
GGT, U/LULN: 52 U/L (M) 38 U/L (F)
287.5 ± 249.6
269.0 ± 240.0
Prior PBC medications
UDCA
65 (100)
128 (100)
OCA use, n (%)
10 (15.4)
15 (11.7)
Select concomitant use by category¶#**¶#**
Lipid-modifying agents††††
27 (41.5)
40 (31.3)
31% taking lipid- modifying agents††
31% taking lipid-modifying agents††
Drugs for acid- related disorders
21 (32.3)
47 (36.7)
¶Safety analysis set: 128 patients in the LIVDELZI arm and 65 patients in the placebo arm.4,5
#Medications for pruritus were allowed in the study if patients had been on a stable dose for 1 month prior to screening or upon discussion with the medical monitor.4
**Reported by Anatomical Classification level 2 terms.4
††Bile acid sequestrants: Administer LIVDELZI at least 4 hours before or 4 hours after taking a bile acid sequestrant, or at as great an interval as possible.1
76% biochemical response rate at 12 months observed in a prespecified, exploratory subgroup analysis2,6
ALP of 350 U/L is ~3 x ULN1
Biochemical response by ALP level: <350 and ≥350 U/L6
ALP <350 U/L at baseline
76% of patients in the LIVDELZI arm had a biochemical response rate at 12 months vs 23% in the placebo arm (risk difference: 52.9% [95% CI: 36.4, 66.0])6
ALP ≥350 U/L at baseline
23% of patients in the LIVDELZI arm had a biochemical response rate at 12 months vs 11% in the placebo arm (risk difference: 11.7% [95% CI: -12.9, 31.0])6
This analysis is descriptive only and multiplicity was not controlled.2
Biochemical response: ALP <350 U/L6
ALP <350 U/L at baseline
76% of patients in the LIVDELZI arm had a biochemical response rate at 12 months vs 23% in the placebo arm (risk difference: 52.9% [95% CI: 36.4, 66.0])6
This analysis is descriptive only and multiplicity was not controlled.2
Biochemical response: ALP ≥350 U/L6
ALP ≥350 U/L at baseline
23% of patients in the LIVDELZI arm had a biochemical response rate at 12 months vs 11% in the placebo arm (risk difference: 11.7% [95% CI: -12.9, 31.0])6
This analysis is descriptive only and multiplicity was not controlled.2
Important Safety Information
Adverse Reactions
The most common adverse reactions (≥5%) with LIVDELZI were headache (8%), abdominal pain (7%), nausea (6%), abdominal distension (6%), and dizziness (5%).
Please see additional Important Safety Information below.
Observed biochemical response in an open-label, pooled analysis7
ASSURE is an ongoing, open-label extension (OLE) study evaluating the long-term efficacy and safety results of LIVDELZI. Patients from both arms of the pivotal RESPONSE study or those who were enrolled in a prior LIVDELZI PBC clinical study (legacy studies) were invited to participate in ASSURE. Interim 30-month efficacy and safety results have been reported in a pooled analysis.7
This is a descriptive analysis and was not designed with statistical control.
Observed biochemical response7
Composite biochemical response rate achieved in7:
73%
of patients at 12 months
(n/N=204/280)
73%
of patients at 24 months
(n/N=90/124)
81%
of patients at 30 months
(n/N=30/37)
ASSURE is an ongoing, open-label extension (OLE) study evaluating the long-term efficacy and safety results of LIVDELZI. Patients from both arms of the pivotal RESPONSE study or those who were enrolled in a prior LIVDELZI PBC clinical study (legacy studies) were invited to participate in ASSURE. Interim 30-month efficacy and safety results have been reported in a pooled analysis.7*
ASSURE phase 3 open-label study design7,8
Inclusion criteria:
Participated in a PBC study with LIVDELZI
Exclusion criteria†:
AST or ALT >3 x ULN
Total bilirubin >2 x ULN
MELD score ≥12
Evidence of advanced PBC
eGFR ≤45 mL/min/1.73 m2
Use of certain other treatments within 2-3 months prior to screening
History of malignancy diagnosed or treated within 2 years
Use of immunosuppressant therapies
Evidence of advanced PBC
eGFR ≤45 mL/min/1.73 m2
Use of certain other treatments within 2-3 months prior to screening
History of malignancy diagnosed or treated within 2 years
Use of immunosuppressant therapies
Initial data were reported based on exposure to LIVDELZI either upon entry to ASSURE or RESPONSE.
*Data cutoff of January 31, 2024.7
†Exclusion criteria are only applicable when patients have a study drug interruption of >4 weeks prior to day 1 and for patients who participated in the Phase 1b Hepatic Impairment Study.8
‡Legacy seladelpar studies include Phase 2 Dose-Ranging Study (NCT02955602), Phase 3 Long-Term Safety Study (NCT03301506), Phase 3 ENHANCE (NCT03602560), and Phase 1b Hepatic Impairment Study (NCT04950764). Most patients from legacy studies had a treatment gap between their initial use of LIVDELZI and entering the ASSURE study.7,8
§Patients from the placebo arm of the RESPONSE pivotal study switched to active treatment with LIVDELZI in the ASSURE study.8
¶54 patients rolled over from the RESPONSE placebo arm and 104 patients rolled over from the RESPONSE LIVDELZI 10 mg arm.7
Important Safety Information
Warnings and Precautions
Fractures: Fractures occurred in 4% of LIVDELZI-treated patients compared to no placebo-treated patients. Consider the risk of fracture in the care of patients treated with LIVDELZI and monitor bone health according to current standards of care.
Please see additional Important Safety Information below.
ALP data
LIVDELZI is the only PBC treatment that achieved ALP normalization in 25% of patients at 12 months1
RESPONSE was a 12-month, randomized, double-blind phase 3 pivotal trial that assessed the efficacy and safety of LIVDELZI 10 mg ± UDCA (n=128) vs placebo ± UDCA (n=65), administered once daily.1
Help your patients achieve normal ALP with the only PBC treatment to achieve this rate of response1,9
ALP normalization (ALP ≤1.0 x ULN) at 12 months1
Key secondary endpoint1: ALP normalization (ALP ≤1.0 x ULN) at 12 months
In the RESPONSE trial, 12 patients (6%) were intolerant to UDCA and initiated treatment as monotherapy: 8 patients (6%) in the LIVDELZI 10 mg arm and 4 patients (6%) in the placebo arm.1
ALP normalization (ALP ≤1.0 x ULN) at 12 months1
Key secondary endpoint1: ALP normalization (ALP ≤1.0 x ULN) at 12 months
In the RESPONSE trial, 12 patients (6%) were intolerant to UDCA and initiated treatment as monotherapy: 8 patients (6%) in the LIVDELZI 10 mg arm and 4 patients (6%) in the placebo arm.1
Aim for ALP normalization with LIVDELZI1
Primary endpoint1
Composite biochemical response at 12 months:
ALP <1.67 x ULN
≥15% decrease in ALP from baseline
TB ≤1 x ULN
Key secondary endpoints1
ALP normalization at 12 months, defined as ALP ≤1.0 x ULN
Change from baseline in mean pruritus NRS score at 6 months was analyzed using a mixed-effect model for repeated measures‡
Select secondary endpoint2
Mean change in ALP at 12 months
Inclusion criteria1,2
PBC with an inadequate response or intolerance to UDCA (on treatment ≥12 months; last dose >3 months prior to screening)
ALP <1.67 x ULN
TB ≤2 x ULN
ALT/AST ≤3 x ULN
Exclusion criteria1
Other chronic liver diseases
Clinically important hepatic decompensation
Portal hypertension with complications
Cirrhosis with complications (MELD score ≥12, known esophageal varices or variceal bleeds, history of hepatorenal syndrome)
After 12 months, patients from both arms of the RESPONSE trial could enroll in an open-label, long-term study2
*Patients were randomized in a 2:1 ratio.1
†LIVDELZI or placebo was administered in combination with UDCA in 181 (94%) patients during the trial, or as a monotherapy in 12 (6%) patients who were unable to tolerate UDCA.1
‡The pruritus NRS is a scale ranging from 0 (no itch) to 10 (worst itch imaginable).1
LIVDELZI was evaluated in a broad range of patients with PBC2,4
Select baseline demographics and characteristics1,2,4,5
Mean ± SD
Placebo ± UDCA n=65 (%)
LIVDELZI 10 mg ± UDCAn=128 (%)
Female, n (%)
60 (92.3)
123 (96.1)
Age, years
57.0 ± 9.2
56.6 ± 10.0
Duration of disease, years
8.6 ± 6.5
8.2 ± 6.7
Compensated cirrhosis, n (%)
9 (13.8)
18 (14.1)
14% compensated cirrhosis
14% compensated cirrhosis
On UDCA, n (%)
61 (93.8)
120 (93.8)
Pruritus NRS ≥4, n (%)
23 (35.4)
49 (38.3)
Hx of osteopenia, n (%)
8 (12.3)
17 (13.3)
13% or 14% history of osteopenia or osteoporosis
Hx of osteoporosis, n (%)
5 (7.7)
18 (14.1)
13% or 14% history of osteopenia or osteoporosis
Liver function values
ALP, U/LULN: 116 U/L
313.8 ± 117.7
314.6 ± 123.0
ALP ≥350 (3 x ULN), n (%)
18 (27.7)
35 (27.3)
ALP <350 U/L, n (%)
47 (72.3)
93 (72.7)
TB, mg/dLULN: 1.1 mg/dL
0.74 ± 0.3
0.77 ± 0.3
TB >1 x ULN & ≤2 x ULN, n (%)
5 (7.7)
20 (15.6)
ALT, U/LULN: 41 U/L
48.2 ± 22.8
47.4 ± 23.5
AST, U/LULN: 34 U/L
41.7 ± 16.0
39.6 ± 16.1
GGT, U/LULN: 52 U/L (M) 38 U/L (F)
287.5 ± 249.6
269.0 ± 240.0
Prior PBC medications
UDCA
65 (100)
128 (100)
OCA use, n (%)
10 (15.4)
15 (11.7)
Select concomitant use by category§¶#§¶#
Lipid-modifying agents****
27 (41.5)
40 (31.3)
31% taking lipid- modifying agents**
31% taking lipid-modifying agents**
Drugs for acid- related disorders
21 (32.3)
47 (36.7)
§Safety analysis set: 128 patients in the LIVDELZI arm and 65 patients in the placebo arm.4,5
¶Medications for pruritus were allowed in the study if patients had been on a stable dose for 1 month prior to screening or upon discussion with the medical monitor.4
#Reported by Anatomical Classification level 2 terms.4
**Bile acid sequestrants: Administer LIVDELZI at least 4 hours before or 4 hours after taking a bile acid sequestrant, or at as great an interval as possible.1
A rapid and sustained reduction in ALP1
Secondary endpoint2: Mean reduction in ALP over 12 months
There was a trend of lower ALP in the LIVDELZI arm compared with the placebo arm, with LIVDELZI demonstrating rapid and sustained reductions in ALP to <1.67 x ULN with mean (95% CI) levels1,2:
ALP change from baseline1,2
Mean ALP reduction at months 1, 3, 6, 9, and 12 were secondary endpoints. For these endpoints, multiplicity was not controlled.1,2
84% of patients
on LIVDELZI had a ≥15% decrease in ALP at 12 months vs 32% of patients in the placebo arm.1
81% of patients in the LIVDELZI arm achieved TB ≤1 x ULN at 12 months vs 77% of patients in the placebo arm.1
In the RESPONSE trial, 12 patients (6%) were intolerant to UDCA and initiated treatment as monotherapy: 8 patients (6%) in the LIVDELZI 10 mg arm and 4 patients (6%) in the placebo arm.1
Observed ALP normalization rates in an open-label, pooled analysis7
ASSURE is an ongoing, open-label extension (OLE) study evaluating the long-term efficacy and safety results of LIVDELZI. Patients from both arms of the pivotal RESPONSE study or those who were enrolled in a prior LIVDELZI PBC clinical study (legacy studies) were invited to participate in ASSURE. Interim 30-month efficacy and safety results have been reported in a pooled analysis.7
This is a descriptive analysis and was not designed with statistical control.
Observed ALP normalization7
ALP normalization was achieved in7:
38%
of patients at 12 months
(n/N=106/280)
38%
of patients at 24 months
(n/N=47/124)
41%
of patients at 30 months
(n/N=15/37)
ASSURE is an ongoing, open-label extension (OLE) study evaluating the long-term efficacy and safety results of LIVDELZI. Patients from both arms of the pivotal RESPONSE study or those who were enrolled in a prior LIVDELZI PBC clinical study (legacy studies) were invited to participate in ASSURE. Interim 30-month efficacy and safety results have been reported in a pooled analysis.7*
ASSURE phase 3 open-label study design7,8
Inclusion criteria:
Participated in a PBC study with LIVDELZI
Exclusion criteria†:
AST or ALT >3 x ULN
Total bilirubin >2 x ULN
MELD score ≥12
Evidence of advanced PBC
eGFR ≤45 mL/min/1.73 m2
Use of certain other treatments within 2-3 months prior to screening
History of malignancy diagnosed or treated within 2 years
Use of immunosuppressant therapies
Evidence of advanced PBC
eGFR ≤45 mL/min/1.73 m2
Use of certain other treatments within 2-3 months prior to screening
History of malignancy diagnosed or treated within 2 years
Use of immunosuppressant therapies
Initial data were reported based on exposure to LIVDELZI either upon entry to ASSURE or RESPONSE.
*Data cutoff of January 31, 2024.7
†Exclusion criteria are only applicable when patients have a study drug interruption of >4 weeks prior to day 1 and for patients who participated in the Phase 1b Hepatic Impairment Study.8
‡Legacy seladelpar studies include Phase 2 Dose-Ranging Study (NCT02955602), Phase 3 Long-Term Safety Study (NCT03301506), Phase 3 ENHANCE (NCT03602560), and Phase 1b Hepatic Impairment Study (NCT04950764). Most patients from legacy studies had a treatment gap between their initial use of LIVDELZI and entering the ASSURE study.7,8
§Patients from the placebo arm of the RESPONSE pivotal study switched to active treatment with LIVDELZI in the ASSURE study.8
¶54 patients rolled over from the RESPONSE placebo arm and 104 patients rolled over from the RESPONSE LIVDELZI 10 mg arm.7
Pruritus data
For patients with baseline average pruritus NRS score ≥41
LIVDELZI is the only PBC treatment with statistically significant pruritus improvement at 6 months in the FDA-approved label1
RESPONSE was a 12-month, randomized, double-blind phase 3 pivotal trial that assessed the efficacy and safety of LIVDELZI 10 mg ± UDCA (n=128) vs placebo ± UDCA (n=65), administered once daily.1
Key secondary endpoint1: Change in pruritus NRS at 6 months in patients with baseline average pruritus score ≥4.
Reduction in pruritus with LIVDELZI was1,2:
A single-item, patient-reported outcome, the pruritus NRS, evaluated patients’ daily worst itching intensity on an 11-point rating scale, with scores ranging from 0 (“no itching”) to 10 (“worst itching imaginable”) in RESPONSE. The pruritus NRS was administered daily in a 14-day run-in period prior to randomization through 6 months and then for 7 consecutive days during each month up to the end of the treatment period.1,2
Change from baseline in pruritus NRS in patients with baseline average pruritus score ≥41,2
Pruritus NRS is a validated itch scale recognized by the FDA to measure the statistical significance or pruritus improvement in clinical trials10
Pruritus NRS scores at 1 and 9 months were exploratory endpoints and at 3 and 12 months were secondary endpoints. For these endpoints, multiplicity was not controlled.2
The baseline average pruritus score for each patient was calculated by averaging the pruritus NRS scores administered in the run-in period and on Day 1 before treatment initiation. The pruritus scores at 6 months for each patient were calculated by averaging the pruritus NRS scores within the last week in the month.1
Primary endpoint1
Composite biochemical response at 12 months:
ALP <1.67 x ULN
≥15% decrease in ALP from baseline
TB ≤1 x ULN
Key secondary endpoints1
ALP normalization at 12 months, defined as ALP ≤1.0 x ULN
Change from baseline in mean pruritus NRS score at 6 months was analyzed using a mixed-effect model for repeated measures‡
Select secondary endpoint2
Mean change in ALP at 12 months
Inclusion criteria1,2
PBC with an inadequate response or intolerance to UDCA (on treatment ≥12 months; last dose >3 months prior to screening)
ALP <1.67 x ULN
TB ≤2 x ULN
ALT/AST ≤3 x ULN
Exclusion criteria1
Other chronic liver diseases
Clinically important hepatic decompensation
Portal hypertension with complications
Cirrhosis with complications (MELD score ≥12, known esophageal varices or variceal bleeds, history of hepatorenal syndrome)
After 12 months, patients from both arms of the RESPONSE trial could enroll in an open-label, long-term study2
*Patients were randomized in a 2:1 ratio.1
†LIVDELZI or placebo was administered in combination with UDCA in 181 (94%) patients during the trial, or as a monotherapy in 12 (6%) patients who were unable to tolerate UDCA.1
‡The pruritus NRS is a scale ranging from 0 (no itch) to 10 (worst itch imaginable).1
LIVDELZI was evaluated in a broad range of patients with PBC2,4
Select baseline demographics and characteristics1,2,4,5
Mean ± SD
Placebo ± UDCA n=65 (%)
LIVDELZI 10 mg ± UDCAn=128 (%)
Female, n (%)
60 (92.3)
123 (96.1)
Age, years
57.0 ± 9.2
56.6 ± 10.0
Duration of disease, years
8.6 ± 6.5
8.2 ± 6.7
Compensated cirrhosis, n (%)
9 (13.8)
18 (14.1)
14% compensated cirrhosis
14% compensated cirrhosis
On UDCA, n (%)
61 (93.8)
120 (93.8)
Pruritus NRS ≥4, n (%)
23 (35.4)
49 (38.3)
Hx of osteopenia, n (%)
8 (12.3)
17 (13.3)
13% or 14% history of osteopenia or osteoporosis
Hx of osteoporosis, n (%)
5 (7.7)
18 (14.1)
13% or 14% history of osteopenia or osteoporosis
Liver function values
ALP, U/LULN: 116 U/L
313.8 ± 117.7
314.6 ± 123.0
ALP ≥350 (3 x ULN), n (%)
18 (27.7)
35 (27.3)
ALP <350 U/L, n (%)
47 (72.3)
93 (72.7)
TB, mg/dLULN: 1.1 mg/dL
0.74 ± 0.3
0.77 ± 0.3
TB >1 x ULN & ≤2 x ULN, n (%)
5 (7.7)
20 (15.6)
ALT, U/LULN: 41 U/L
48.2 ± 22.8
47.4 ± 23.5
AST, U/LULN: 34 U/L
41.7 ± 16.0
39.6 ± 16.1
GGT, U/LULN: 52 U/L (M) 38 U/L (F)
287.5 ± 249.6
269.0 ± 240.0
Prior PBC medications
UDCA
65 (100)
128 (100)
OCA use, n (%)
10 (15.4)
15 (11.7)
Select concomitant use by category§¶#§¶#
Lipid-modifying agents****
27 (41.5)
40 (31.3)
31% taking lipid- modifying agents**
31% taking lipid-modifying agents**
Drugs for acid- related disorders
21 (32.3)
47 (36.7)
§Safety analysis set: 128 patients in the LIVDELZI arm and 65 patients in the placebo arm.4,5
¶Medications for pruritus were allowed in the study if patients had been on a stable dose for 1 month prior to screening or upon discussion with the medical monitor.4
#Reported by Anatomical Classification level 2 terms.4
**Bile acid sequestrants: Administer LIVDELZI at least 4 hours before or 4 hours after taking a bile acid sequestrant, or at as great an interval as possible.1
Review the safety and tolerability profile of LIVDELZI
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). Improvement in survival or prevention of liver decompensation events have not been demonstrated. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
Limitation of use: Use of LIVDELZI is not recommended in patients who have or develop decompensated cirrhosis (eg, ascites, variceal bleeding, hepatic encephalopathy).
IMPORTANT SAFETY INFORMATION
Warnings and Precautions
Fractures: Fractures occurred in 4% of LIVDELZI-treated patients compared to no placebo-treated patients. Consider the risk of fracture in the care of patients treated with LIVDELZI and monitor bone health according to current standards of care.
Liver Test Abnormalities: LIVDELZI has been associated with dose-related increases in serum transaminase (AST and ALT) levels >3x ULN in patients receiving 50 mg and 200 mg once daily (5x and 20x higher than the recommended dosage of 10 mg once daily). Perform baseline clinical and laboratory testing when starting LIVDELZI and monitor thereafter according to routine patient management. Interrupt treatment if the liver tests (ALT, AST, total bilirubin, and/or ALP) worsen, or if the patient develops signs and symptoms of clinical hepatitis (eg, jaundice, right upper quadrant pain, eosinophilia). Consider permanent discontinuation if liver tests worsen after restarting LIVDELZI.
Biliary Obstruction: Avoid use of LIVDELZI in patients with complete biliary obstruction. If biliary obstruction is suspected, interrupt LIVDELZI and treat as clinically indicated.
Adverse Reactions
The most common adverse reactions (≥5%) with LIVDELZI were headache (8%), abdominal pain (7%), nausea (6%), abdominal distension (6%), and dizziness (5%).
Drug Interactions
OAT3 Inhibitors and Strong CYP2C9 Inhibitors: Avoid coadministration with LIVDELZI due to increased LIVDELZI exposure.
Rifampin: Monitor biochemical response (eg, ALP and bilirubin) when patients initiate rifampin during LIVDELZI treatment. Coadministration may result in delayed or suboptimal biochemical response of LIVDELZI.
Dual Moderate CYP2C9 and Moderate-to-Strong CYP3A4 Inhibitors and BCRP Inhibitors (eg, cyclosporine): Monitor closely for adverse effects. Concomitant administration with LIVDELZI may increase LIVDELZI exposure.
CYP2C9 Poor Metabolizers Using Moderate-to-Strong CYP3A4 Inhibitors: Monitor more frequently for adverse reactions as concomitant use of a moderate-to-strong CYP3A4 inhibitor in patients who are CYP2C9 poor metabolizers may increase LIVDELZI exposure and risk of LIVDELZI adverse reactions.
Bile Acid Sequestrants: Administer LIVDELZI at least 4 hours before or 4 hours after taking a bile acid sequestrant, or at as great an interval as possible.
Pregnancy and Lactation
Pregnancy: There are insufficient data from human pregnancies exposed to LIVDELZI to allow an assessment of a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Report pregnancies to Gilead Sciences, Inc., at 1-800-445-3235.
Lactation: There are no data on the presence of LIVDELZI in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for LIVDELZI and any potential adverse effects on the breastfed infant from LIVDELZI.
LIVDELZI [prescribing information]. Foster City, CA: Gilead Sciences, Inc.; 2024.
Hirschfield GM, Bowlus CL, Mayo MJ, et al; RESPONSE Study Group. A phase 3 trial of seladelpar in primary biliary cholangitis. N Engl J Med. 2024;390(9):783-794. doi:10.1056/NEJMoa2312100
Lammers WJ, van Buuren HR, Hirschfield GM, et al. Levels of alkaline phosphatase and bilirubin are surrogate end points of outcomes of patients with primary biliary cirrhosis: an international follow-up study. Gastroenterology. 2014;147(6):1338-1349.e5. doi:10.1053/j.gastro.2014.08.029
Hirschfield GM, Bowlus CL, Mayo MJ, et al; RESPONSE Study Group. A phase 3 trial of seladelpar in primary biliary cholangitis [supplementary appendix]. N Engl J Med. 2024;390(9):783-794. doi:10.1056/NEJMoa2312100
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