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LYVDELZI (seladelpar) is indicated for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA alone, or as monotherapy in those unable to tolerate UDCA.1
Product Information for LYVDELZI (seladelpar) 10 mg oral capsule.
LYVDELZI is the first and only PBC treatment that achieved clinically and statistically significant reductions across PBC biomarkers AND pruritus intensity vs placebo.1-3
In RESPONSE, a multicentred, double-blind, placebo-controlled trial, LYVDELZI helped to:*
LOWER
key PBC biomarker levels1,2,4
62% of patients achieved composite biochemical response at 12 months†1,2
LOWER
ALP levels to normal1,2,4
25% of patients achieved ALP normalisation at 12 months‡1,2
LOWER
pruritus intensity1,2,4
Rapid improvement by 1 month in patients with NRS ≥4 at baseline, with statistically significant reduction at 6 months§1,2
Key secondary endpoints: ALP normalisation at 12 months and change in pruritus NRS score from baseline to 6 months among patients with NRS ≥4 at baseline.1,2 For full inclusion criteria, see: Hirschfield GM, et al. N Engl J Med 2024;390(9):783–794.
A 12-month, randomised, double-blind, placebo-controlled trial in 193 adults (aged 18–75 years) who had an inadequate response to, or a history of unacceptable side effects with, UDCA.1,2
Endpoints
Primary1
Composite biochemical response at 12 months:
- ALP <1.67 x ULN
- ≥15% decrease in ALP from baseline
- TB ≤1 x ULN
Key secondary1
- ALP normalisation at 12 months, defined as ALP ≤1.0 x ULN
- Change from baseline in mean pruritus NRS score at 6 months was analysed using a mixed-effect model for repeated measures‡
Select secondary2
- Mean change in ALP at 12 months
Inclusion criteria:1
- 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 criteria:1
- Other chronic liver disease
- Clinically important hepatic decompensation
- Portal hypertension with complications
- Cirrhosis with complications (MELD score ≥12, known oesophageal varices or history of variceal bleeds, history of hepatorenal syndrome)
- * Patients were randomised in a 2:1 ratio.1
- † LYVDELZI 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
ABOUT LYVDELZI
LYVDELZI is the first and only selective PPAR delta agonist for PBC*1,3
PPAR delta is a nuclear receptor expressed in the liver and other tissues1
PPAR delta activation reduces bile acid synthesis through FGF21-dependent down regulation of CYP7A1 (the key enzyme for synthesis of bile acids from cholesterol)1
LYVDELZI is designed to potently and selectively target PPAR delta, helping to:1,5
Reduce synthesis of bile acids from cholesterol
Decrease cholesterol synthesis and absorption
Lower bile acid exposure in the liver
Reduce circulating bile acid levels
EFFICACY – Biochemical levels
LYVDELZI lowered key PBC biochemical levels1,2
62% of patients achieved composite biochemical response with LYVDELZI at 12 months*1,2
Patients achieving composite biochemical response at 12 months
(ALP <1.67 x ULN, ≥15% ALP decrease from baseline, TB ≤1.0 x ULN; primary endpoint)†1,2
EFFICACY – ALP normalisation
LYVDELZI lowered ALP levels1,2
LYVDELZI is the only PBC treatment to achieve 25% ALP normalisation rate after 12 months*1,2
Patients achieving ALP normalisation at 12 months
(ALP ≤1.0 x ULN; secondary endpoint)†1,2
Rapid reduction observed as early as 1 month1,2
Improvement sustained through 12 months1,2
84% (n=108/128) of patients on LYVDELZI
had ≥15% decrease in ALP at 12 months vs 32% (n=21/66) on placebo1
EFFICACY – Pruritus intensity and patient reported outcomes
LYVDELZI lowered pruritus intensity1,2
LYVDELZI is the only PBC treatment that significantly reduces moderate-to-severe pruritus intensity at 6 months*†1,2
Change from baseline in pruritus intensity in patients with NRS ≥4‡1,2
Significantly reduced pruritus intensity at 6 months
(p=0.005; secondary endpoint)1,2
Rapid reduction observed as early as 1 month1,2
Sustained improvements through 12 months2
At 6 months, treatment with LYVDELZI in patients with moderate-to-severe pruritus (NRS ≥4) was associated with:
-2.2
Reduction in PBC-40 Itch domain score*1,2,7
Change in PBC-40 Itch domain score from baseline vs placebo: -2.2 vs -0.40 (ETD, -1.8%; 95% CI, -3.2 to -0.39) at 6 months, respectively.1
-4.7
Reduction in 5-D Itch scale†1,2,7
Change in 5-D Itch scale from baseline vs placebo: -4.7 vs -1.3 (ETD, -3.4%; 95% CI, -5.3 to -1.5) at 6 months, respectively.1
PBC-40 and 5-D Itch quality of life measures
PBC-40 is a validated health-related quality-of-life questionnaire designed to quantify the impact of PBC across six domains.8 The PBC-40 itch domain asks patients how often they experienced itching in the last four weeks. Answers are rated on a scale from 'never' to 'always' across:8
- Itching disturbed my sleep
- I scratched so much I made my skin raw
- I felt embarrassed because of the itching
5-D Itch is a validated, multidimensional measure of itching, designed to assess impact of pruritus across five domains.9 Five domains include: degree, duration, direction (improvement or worsening), disability (effect on daily activities) and distribution of itching.7
SAFETY
Response study: summary of adverse effects
The safety population included patients without cirrhosis and with compensated cirrhosis.2,7
3.1% of patients discontinued with LYVDELZI treatment due to AEs (vs 4.6% patients with placebo).2
SmPC: frequency of adverse effects
LYVDELZI has been studied in a broad population of over 200 patients, with a wide range of concomitant medications.1,2,7,10
Additional monitoring of adverse effects1
- No clinically relevant effect on the pharmacokinetics of statins, simvastatin, atorvastatin and rosuvastatin1
- No evidence of foetal toxicity in animal studies and no requirement for concomitant use of contraception in women of childbearing potential‡1
- No additional monitoring requirements for blood CPK increases or unexplained muscle injury1
- No pattern for increases in transaminases levels observed at recommended 10 mg/day dose1
Contraindications
- Hypersensitivity to the active substance or excipients1
Special warnings and precautions for use
- Evidence of increases in transaminases levels observed in patients receiving higher doses (5x or 20x the recommended dose) of LYVDELZI1
- Avoid use of LYVDELZI in patients with complete biliary obstruction1
- LYVDELZI contains <1 mmol sodium (23 mg) per capsule1
Drug interactions
- Probenicid – co-administration of probenecid (an OAT1, OAT3 and OATP1B1-inhibitor) with LYVDELZI is not recommended1
- Drug transporter inhibitors – concomitant
administration of LYVDELZI with dual or multiple clinical inhibitors of
drugs transporters including BCRP, OATP1B1, OATP1B3 and OAT3 (such as cyclosporine)
may increase LYVDELZI exposure.1
Patients should be closely monitored for adverse effects1 - CYP2C9 and CYP3A4 inhibitors – concomitant administration of LYVDELZI with strong CYP2C9 inhibitors, or dual moderate CYP2C9 and moderate-to-strong CYP3A4 inhibitors (such as fluconazole, mifepristone) may result in an increase in LYVDELZI exposure.1 Patients should be closely monitored for adverse effects1
- CYP2C9 inducers and strong CYP3A4 inducers – concomitant administration of LYVDELZI with CYP2C9 inducers and strong CYP3A4 inducers (such as rifampicin) can decrease LYVDELZI exposure.1 Patients should be monitored for a potential reduction in efficacy1
- Bile acid binding resins – bile acid binding resins (such as cholestyramine, colestipol, or colesevelam) may reduce absorption of other medicinal products administered concurrently.1 Patients should take LYVDELZI at least 4 hours before or 4 hours after taking a bile acid binding resin1
Abbreviations
- AE, adverse event;
- ALP, alkaline phosphatase;
- ALT, alanine transaminase;
- AST, aspartate transaminase;
- CI, confidence interval;
- CPK, creatine phosphokinase;
- CYP7A1, Cytochrome P450 7A1;
- FGF-21, Fibroblast growth factor-21;
- ETD, estimated treatment difference;
- LSM, least squares mean;
- MELD, model for end-stage liver disease;
- NRS, numerical rating scale;
- PBC, primary biliary cholangitis;
- PBC-40, primary biliary cholangitis-40;
- PPAR, peroxisome proliferator-activated receptors;
- SE, standard error;
- SmPC, Summary of Product Characteristics;
- TB, total bilirubin;
- ULN, upper limit of normal;
- UDCA, ursodeoxycholic acid;
- 5-D Itch, 5-dimensions itch.
References
- Lyvdelzi (seladelpar) SmPC [March 2025].
- Hirschfield GM, et al. N Engl J Med 2024;390(9):783–794.
- Jones D, et al. Lancet Gastroenterol Hepatol 2017;2(10):716–726.
- EASL Clinical Practice Guidelines. J Hepatol 2017;67(1):145–172.
- Kamata S, et al. Antioxidants 2023;12(8):1523.
- Storck M, et al. J EurAcad Dermatol Venereol 2021;35(5):1176–1185.
- Hirschfield GM, et al. N Engl J Med 2024;390(9 Suppl.):S31–65.
- Jacoby A, et al Gut 2005;54(11):1622–9.
- Elman S, et al. Br J Dermatol. 2010;162(3):587–93.
- Hirschfield GM, et al. Hepatology 2023;78(2):397–415.
▼ This medicinal product is subject to additional monitoring.