Navigating Treatment for a Patient with PBC: A Personalised Approach
Interactive Case Study This material is intended for healthcare professionals only in the EU-EEA area and Switzerland. This interactive case study was organised and funded by Gilead Sciences, Inc. This material mentions Lyvdelzi®▼ (seladelpar). EU SmPC for seladelpar can be found here. Prescribing information or conditions may vary from country to country, please refer to your relevant regulatory information.
START
▼This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Any suspected adverse reactions to Lyvdelzi® (seladelpar) should be reported to Gilead safety at safety_FC@gilead.com and to your national reporting system.
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Hepatology
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Disclosure
These interactive case studies were developed with support from Gilead Sciences, Inc.
Disclaimer
Lyvdelzi®▼(seladelpar) was granted conditional approval by the EC for the treatment of PBC in combination with UDCA in adults who have an inadequate response to UDCA alone, or as monotherapy in those unable to tolerate UDCA.1
EC: European Commission; PBC: primary biliary cholangitis; UDCA: ursodeoxycholic acid.
▼This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.
References
Iqirvo®▼(Elafibranor) was granted conditional approval by the EC for the treatment of PBC in combination with UDCA in adults who have an inadequate response to UDCA alone, or as monotherapy in those unable to tolerate UDCA.2
These are hypothetical patient cases and outcomes may not be reflective of clinical studies or real-life circumstances. These materials include reference to agents that may be used off-label or for unlicensed indications. The mention of these agents and their uses is intended solely for educational purposes and should not be considered an endorsement or recommendation for their use outside approved indications. Please always consult guidelines and local prescribing information in your country of practice, as information may vary.
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1. European Medicines Agency. Lyvdelzi [Summary of Product Characteristics]. Available at: https://www.ema.europa.eu/en/documents/product-information/lyvdelzi-epar-product-information_en.pdf. Last accessed: 2 March 2026. 2. European Medicines Agency. Iqirvo [Summary of Product characteristics]. Available at: https://www.ema.europa.eu/en/documents/product-information/iqirvo-epar-product-information_en.pdf. Last accessed: 2 March 2026.
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Meet Jenny
ALP: alkaline phosphatase; PBC: primary biliary cholangitis; UDCA: ursodeoxycholic acid.
This is a fictitious patient.
Prior to her PBC diagnosis, Jenny initially presented with itchy skin, fatigue, and discomfort in the upper right side of her abdomen. Her initial labs showed an elevated ALP (345 IU/L) and bilirubin (1.32 mg/dL)
Jenny is 45 years old with two young children (4 and 8 years old)
The hepatologist evaluates Jenny and confirms her PBC remains uncontrolled.
She was then prescribed UDCA, and has been on this treatment for 1.5 years.
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Jenny’s Current Condition
UDCA: ursodeoxycholic acid.
Upon diagnosis, Jenny commenced UDCA (weight based, 13–15 mg/kg) and has remained on UDCA therapy for 1.5 years.
Although her ALP and bilirubin levels have improved, they remain high (230 IU/L and 1.22 mg/dL, respectively).
When should 2L treatment be considered?
2L: second-line; ALP: alkaline phosphatase.
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Current Guideline-Recommended Treatments for PBC
1L: first-line; 2L: second-line; M: months; PBC: primary biliary cholangitis; UDCA: ursodeoxycholic acid.
1. European Association for the Study of the Liver. J Hepatol. 2017;67(1):145-72. 2. Lindor KD et al. Hepatology. 2019;69(1):394-419. 3. Younossi ZM et al. Am J Gastroenterol. 2019;114(1):48-63. 4. Hong Y et al. Hepatol Int. 2022;16(1):1-23. 5. European Medicines Agency. Lyvdelzi [Summary of Product Characteristics] Available at: https://www.ema.europa.eu/en/documents/product-information/lyvdelzi-epar-product-information_en.pdf. Last accessed: 2 March 2026. 6. European Medicines Agency. Iqirvo [Summary of Product characteristics]. Available at: https://www.ema.europa.eu/en/documents/product-information/iqirvo-epar-product-information_en.pdf. Last accessed: 2 March 2026.
Current Treatment Paradigm1-4
UDCA (13–15 mg/kg/day)
Assess biological response at 6 M–1 year
UDCA responder
Inadequate response to UDCA
Intolerant to UDCA
Continue UDCA
Add on 2L therapy
Switch to 2L monotherapy
Monitor response
Guidelines recommend 2L therapy should be added to UDCA treatment if patient does not achieve adequate response
UDCA Continue patient on UDCA to maintain progress1,2 Discontinue UDCA only if patient has intolerance to UDCA1,2
2L Therapy Consider escalation to a 2L therapy as an add-on to UDCA1,2 Seladelpar and elafibranor are two approved 2L treatment options for PBC5,6 Other treatments include off-label fibrates and pruritus management1,2
Based on the patient’s current clinical profile, which therapy would you initiate as an add-on to UDCA?
Bezafibrate
C
B
Elafibranor
A
Seladelpar
Let's explore the current 2L treatment options
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UDCA: ursodeoxycholic acid; 2L: second-line.
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Current 2L Treatments
Selective PPAR
Non-selective PPARs
Seladelpar▼4
Off-label fibrates
2L treatment for PBC 10 mg oral dose Combination with UDCA in adults who have an inadequate response to UDCA, or Monotherapy in patients unable to tolerate UDCA
EASL 2017 guidelines include fibrates as an off-label 2L treatment option3 A recommendation for therapy cannot be made due to limited evidence3 Contraindicated in significant liver disease, including PBC1
2L treatment for PBC 80 mg oral dose Combination with UDCA in adults who have an inadequate response to UDCA, or Monotherapy in patients unable to tolerate UDCA
▼This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 2L: second-line; EASL: European Association for the Study of the Liver; MoA: mechanism of action; PBC: primary biliary cholangitis; PPAR: peroxisome proliferator-activated receptor; UDCA: ursodeoxycholic acid.
PPARδ
PPARα
PPARγ
M O A
Indiacation
Fibrates for the treatment of PBC are off-label and contraindicated in significant liver disease.1-3
Bezafibrate (mixed-PPAR)5
1. FDA. TRICOR prescribing information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021656s029lbl.pdf. Last accessed: 2 March 2026. 2. Allergan, Inc. BENZALIP SR product monograph. Available at: https://www.abbvie.ca/content/dam/abbvie-dotcom/ca/en/documents/products/BEZALIP_SR_PM_EN.pdf. Last accessed: 2 March 2026. 3. European Association for the Study of the Liver. J Hepatol. 2017;67(1):145-72. 4. European Medicines Agency. Lyvdelzi [Summary of Product Characteristics]. Available at: https://www.ema.europa.eu/en/documents/product-information/lyvdelzi-epar-product-information_en.pdf. Last accessed: 2 March 2026. 5. Tanaka A. Drugs. 2024;84:1-15. 6. European Medicines Agency. Iquirvo [Summary of Product Characteristics]. Available at: https://www.ema.europa.eu/en/documents/product-information/iqirvo-epar-product-information_en.pdf. Last accessed: 2 March 2026. 7. Jones D et al. Lancet Gastroenterol Hepatol. 2017:2(10):716-26.
Elafibranor▼6
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Off-Label Fibrate Discontinuation Pattern1
*Cohort was distributed across the USA, Canada, Argentina, UK, Italy, France, Germany, Spain, Switzerland, Greece, Belgium, the Netherlands, Israel, and Japan. †Decompensation, death due to liver causes, transplantation. 2L: second-line; PBC: primary biliary cholangitis.
High discontinuation rates underscore unmet need with tolerability of 2L off-label fibrates
Background1,2
While fibrates are used off-label: Fenofibrate is contraindicated in PBC3 Bezafibrate is contraindicated in significant liver diseases4
Fibrates: 41.0 (14.0−83.0)
Retrospective, international study of patients on 2L therapy with fibrates (n=887, fenofibrate or bezafibrate)*,2
2L follow-up time, months, median (interquartile range)
Overall discontinuationn=182/887
21%
1. Van Hooff MC et al.; on behalf of the Dutch PBC Cohort Study Group. Am J Gastroenterol. 2025;DOI:10.14309/ajg.0000000000003879. 2. Ronca V et al. Oral Presentation 186. AASLD, 15-19 November, 2024. 3. FDA. 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/021656s032lbl.pdf. Last accessed: 4 December 2025. 4. AbbVie. 2019. Avaliable at: https://www.abbvie.ca/content/dam/abbvie-dotcom/ca/en/documents/products/BEZALIP_SR_PI_EN.pdf. Last accessed: 5 December 2025.
Real-world data indicate that among the 30% of patients with PBC (n=109/317) who discontinued fibrates, 70% (n=76/109) discontinued within the first year of treatment.1
Historically, fibrates have been used off-label for PBC treatment due to a lack of 2L alternatives.1
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RESPONSE Study Design
A completed, Phase III, multicentre, randomised, placebo-controlled study in patients living with PBC
ALP: alkaline phosphatase; ALT: alanine aminotransferase; AST: aspartate aminotransferase; EOS: end of study; M: month; NRS: numerical rating scale; PBC: primary biliary cholangitis; TB: total bilirubin; UDCA: ursodeoxycholic acid; ULN: upper limit of normal; vs: versus.
*5-D Itch and PBC-40 scores were not defined as primary endpoints; they were collected at a single study visit per each time point (M1, M3, M6, etc.).4 †Daily NRS score averaged per week.4 ‡Single week of NRS collection (daily NRS scores averaged) one week per month in M9 and M12.4 §Scores on the pruritus NRS range from 0–10, with 0 indicating no itch and 10 indicating the worst itch imaginable.1
In the RESPONSE study, patients were randomised in a 2:1 ratio to receive either seladelpar or placebo. Seladelpar and placebo were administered with standard-of-care UDCA unless patients had a history of unacceptable side effects.1 Ninety-four percent of patients in the seladelpar arm and ninety-four percent of patients in the placebo arm received concurrent UDCA.1 ALP ULN: 116 U/L;1 TB ULN: 1.1 mg/dL;2 ALT ULN: 41 U/L.1 Select endpoints were stratified by ALP <350 U/L vs ALP ≥350 U/L and Pruritus NRS <4 vs NRS ≥4.
ALP normalisation at M12 Changes in pruritus NRS§ at M6 in patients with moderate-to-severe pruritus (NRS ≥4) at baseline
Composite biochemical response at M12: ALP <1.67x ULN ALP decrease ≥15% TB ≤1.0x ULN
Primary Endpoint1
Secondary Endpoints1
1. Hirschfield GM et al. N Engl J Med. 2024;390:783-94. 2. Supplement to Hirschfield GM et al. N Engl J Med. 2024;390(9):783-94. 3. Gilead Sciences. NCT03301506. https://clinicaltrials.gov/study/NCT03301506. 4. Hirschfield GM et al. Oral Presentation 5015. AASLD, 7-11 November, 2025.
Seladelpar: RESPONSE1
1. Hirschfield GM et al. N Engl J Med. 2024;390:783-94. 2. Hirschfield GM et al. Oral presentation 5002, AASLD, 10-14 November, 2023.
Not head-to-head comparisons; results of individual studies cannot be directly compared, nor conclusions inferred. *Composite biochemical response is defined as ALP <1.67x ULN, ALP decrease ≥15% and TB ≤1.0x ULN. ALP ULN: 116 U/L;1 Total bilirubin ULN: 1.1 mg/dL.2 ALP: alkaline phosphatase; M: month; ULN: upper limit of normal; Tx: treatment; SEL: seladelpar; ELA: elafibranor.
6 in 10 patients treated with seladelpar achieved a composite biochemical response at Month 121,2
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ASSURE Study Design
An ongoing, Phase III, open-label, multicentre, long-term study in patients living with PBC*
1. Pratt D et al. Oral presentation 0213. AASLD, 7-11 November, 2025. 2. Trivedi PJ et al. Poster ST-13. EASL, 5-8 June, 2024. 3. Hirschfield GM et al. Oral presentation 5015. AASLD, 7-11 November, 2025
Long-term safety & tolerability
Primary Endpoint
*The most recent ASSURE data cutoff was 31 January 2025;1 **Legacy studies: Phase III study ENHANCE (NCT03602560), Phase II Dose-Ranging study (NCT02955602), Phase III Long-Term Safety study (NCT03301506), and Phase Ib Hepatic Impairment study (NCT04950764); †5-D Itch and PBC-40 scores were not defined as primary endpoints; they were collected at a single study visit per each time point;3 ‡Daily NRS score averaged per week;3 §Collected at a single visit for each time point beyond M21 of seladelpar exposure in ASSURE (M21, M24, etc). AE: adverse event; M: month; NRS: numerical rating scale; PBC: primary biliary cholangitis; PRO: patient-reported outcome; SEL: seladelpar.
Long-term efficacy PROs
Secondary Endpoints
ASSURE Entry Criteria1 Participation in a previous SEL PBC study (“Legacy studies”) Direct rollover from Phase III RESPONSE pivotal study No AEs leading to discontinuation in a previous SEL study2
*ALP ≤1x ULN (ULN = 116 U/L); **ALP <1.67x ULN (ULN = 116 U/L), ≥15% ALP decrease, and TB ≤1.0x ULN (ULN = 1.10 mg/dL). ALP: alkaline phosphatase; BL: baseline; CBR: composite biochemical response; M: month; SE: standard error; TB: total bilirubin.
Seladelpar: ASSURE (36M)1
Interim analysis from the ongoing Phase III open-label ASSURE study (N=337)
ALP Percent Change from BL
ALP Normalisation*
Composite Biochemical Response**
Seladelpar 10 mg
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1. Pratt D et al. Oral presentation 0213, AASLD. 7-11 November, 2025. 2. Gilead, data on file.
Elafibranor: ELATIVE Study Design1
1. Kowdley KV et al. N Engl J Med. 2024;390(9):795-805.
*Patients continued to receive double-blind treatment beyond Week 52 until all patients had completed their Week 52 assessment, or until a maximum treatment duration of 104 weeks, whichever came first. ALP: alkaline phosphatase; ALT: alanine aminotransferase; AST: aspartate aminotransferase; BL: baseline; DB: double-blind; EOS: end of study; M: month; NRS: numerical rating scale; PBC: primary biliary cholangitis; UDCA: ursodeoxycholic acid; ULN: upper limit of normal.
Phase III, multinational, randomised, placebo-controlled study in patients living with PBC
ALP normalisation at Week 52 Changes in pruritus NRS at Week 16 in patients with moderate-to-severe pruritus (NRS ≥4) at BL
Key Inclusion Criteria
PBC and inadequate response or intolerance to UDCA ALP ≥1.67x ULN ALT and AST ≤3x ULN Total bilirubin ≤2x ULN Non-cirrhotic or compensated cirrhosis
N=161 Randomised 2:1
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Elafibranor: ELATIVE Results1
Not head-to-head comparisons; results of individual studies cannot be directly compared, nor conclusions inferred. ALP ULN: 129 U/L (males), 104 U/L (females); Total bilirubin ULN: 1.2 mg/dL ALP: alkaline phosphatase; M: month; ULN: upper limit of normal; ELA: elafibranor; SEL: seladelpar.
Five in 10 patients treated with elafibranor achieved a composite biochemical response at Month 12
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Elafibranor: ELATIVE OLE (36M)
*ALP <1.67×ULN, ≥15% ALP reduction and TB ≤ULN. **In the double-blind period, patients experiencing an occurrence of an intercurrent event (treatment discontinuation or use of rescue therapy for PBC) were considered as non-responders and data were imputed.2 In the OLE, data observed one day or more after the occurrence of an intercurrent event (treatment discontinuation or use of rescue therapy for PBC) were considered as missing data. †Includes events in the OLE as of May 2025 data cut-off only. AE: adverse event; AKI: acute kidney injury; ALP: alkaline phosphatase; ALT: alanine aminotransferase; BL: baseline; CPK: creatine phosphokinase; ELA: elafibranor; GGT: gamma-glutamyl transferase; OLE: open-label extension; PBC: primary biliary cholangitis; SEL: seladelpar; TB: total bilirubin; TEAE: treatment-emergent AE; ULN: upper limit of normal; UTI: urinary tract infection; Y: year.
Biochemical Response*,1
ALP Normalisation†,2
1. Levy C et al. Oral presentation 5016, AASLD. 7-11 November, 2025. 2. Kowdley KV. N Engl J Med. 2024;390(9):795-805; 3. Pratt D et al. Oral presentation 0213, AASLD. 7-11 November, 2025. 4. Levy C et al. Oral presentation 4434. AASLD. 7-11 November, 2025.
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Which biochemical improvement data is most impactful to you in clinical practice?
All endpoints should be considered when determining biochemical response.
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ALP: alkaline phosphatase; TB: total bilirubin.
Composite biochemical response
ALP normalisation
ALP reduction
D
TB reduction
SUBMIT
Select all that apply
Jenny’s Itch Remains
Her itch remains, and she is worried that it may get worse and may disrupt her sleep.
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Pruritus Prevalence in PBC1
*Clinically significant itch was measured per the PBC-40, which includes itch, fatigue, general symptoms, cognition, social, and emotional domains. PBC: primary biliary cholangitis.
81%
1. Mayo MJ et al. Dig Dis Sci. 2023;68(3):995-1005.
Observational Cohort Study Across the US (N=211)
(170/211) of patients with PBC reported pruritus of any degree
37%
(63/170) of those 170 patients reported clinically significant pruritus*
Pruritus is a prevalent & debilitating symptom seen with PBC
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Pruritus Impact on QoL
PBC: primary biliary cholangitis; QoL: quality of life.
1. Mayo MJ et al. Dig Dis Sci. 2023;68(3):995-1005. 2. Levy C et al. Poster 4274. AASLD, 15-19 November, 2024.
Real-world data from 211 patients with PBC reported disability linked to pruritus across the following 4 key areas:1
Pruritus impacts many aspects of patients’ lives, causing declines in QoL
“It's hard to sleep…I’m itching while at work, which makes it very hard to focus…I’m less productive.”2
“[Itching] does make you want to just hide away from anybody…it just makes you feel isolated in a sense.”2
Sleep
Work/school
Social life
Housework/errands
88%
44%
53%
58%
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Seladelpar: Pruritus
1. Hirschfield GM et al. Oral presentation 5002. AASLD, 10-14 November, 2023. 2. Gilead, data on file.
Key Secondary Endpoint: Change in NRS*
*Change in pruritus NRS through 12 months in patients with moderate-to-severe pruritus (defined as NRS ≥4). †Change in pruritus 5-D itch through 12 months in patients with moderate-to-severe pruritus. †p<0.005 versus placebo. ‡Change in pruritus PBC-40 through 12 months in patients with moderate-to-severe pruritus. BL: baseline; M: month; LS: least-squares; NRS: numerical rating scale; PBC: primary biliary cholangitis; QoL: quality of life; SE: standard error.
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Elafibranor: Pruritus1
Phase III pivotal study ELATIVE (N=161)
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*Treatment with elafibranor was associated with an improvement in pruritus as evidenced by a reduction in the PBC-40 Itch and 5-D Itch total scores compared to placebo at Week 52. BL: baseline; LS: least-squares; NRS: Numeric Rating Scale.
Change in NRS through 52 Weeks in Patients with Moderate-to-Severe Pruritus
Which therapy provides statistically significant improvement in NRS pruritus in patients who have moderate-to-severe pruritus?
Seladelpar + elafibranor are similar
Neither
NRS: Numeric Rating Scale.
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Multifactorial Causes of Fatigue in PBC
PBC: primary biliary cholangitis.
Cholestatic mechanisms of PBC can cause fatigue Autonomic dysfunction1 Pruritus-related sleep disturbance2
Some medications are associated with fatigue, e.g., Antihistamines9 Beta blockers1 Antidepressants1
PBC-associated causes
Comorbidities
Concomitant medications
Fatigue, which affects an estimated 63% of patients with PBC,1 is a multifactorial secondary PBC symptom that may be exacerbated by itch with no approved pharmacological treatment.1,2,5
Comorbidities may contribute to fatigue, e.g., Cardiovascular disease1,3 Autoimmune thyroid disease1,4 Sicca syndrome5,6 Menopause7 Autoimmune hepatitis1,8
1. Koc OM et al. Lancet Gastroenterol Hepatol. 2025;11(1):71-86. 2. Lynch EN et al. World J Hepatol. 2022;14(6):1111-9. 3. Jurgens CY et al. Circulation. 2022;146(12):e173-84. 4. Chaker L et al. Lancet. 2017;390(10101):1550-62. 5. Levy C et al. Clin Gastroenterol Hepatol. 2023;21(8):2076-87. 6. Leung K et al. Poster THU-317-YI. EASL Congress, 7-10 May, 2025. 7. Davis SR et al. Cell. 2023;186(19):4038-58. 8. Wong LL et al. Hepatology. 2018;68(4):1487-97. 9. Church MK, Church DS. Indian J Dermatol. 2013;58(3):219-24.
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*Significance testing was conducted between Mild Itch and CS Itch, p<0.0001. CS: clinically significant; PBC: primary biliary cholangitis; PROMIS: Patient-Reported Outcomes Measurement Information System; vs: versus.
1. Koc OM et al. Lancet Gastroenterol Hepatol. 2025;11(1):71-86. 2. Mayo MJ et al. Dig Dis Sci. 2022;68:995-1005.3. 3. Levy C et al. Clin Gastroenterol Hepatol. 2023;21(8):2076-87.
Fatigue, which affects an estimated 63% of patients with PBC,1 is a multifactorial secondary PBC symptom that may be exacerbated by itch with no approved pharmacological treatment.1-3
PBC-Associated Causes
Patients with clinically significant pruritus had significantly worse fatigue than patients with mild itch (median PROMIS Fatigue scores 61 vs 50, p<0.0001).*,2
Pruritus and fatigue
Pruritus-related sleep disturbance2
Cholestatic mechanisms of PBC can cause fatigue Autonomic dysfunction1
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Jenny wants to be involved in making an informed decision as to what is a suitable 2L therapy for her, expressing her desire to ensure her potential treatment is safe.
Let's explore these considerations
As Jenny’s doctor, which safety considerations do you take into account when selecting a PPAR?
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2L: second-line; PPAR: peroxisome proliferator-activated receptor.
Minimal muscle, renal and liver long-term safety considerations
Minimal impact on women's health
Minimal drug-drug interactions
Low monitoring burden
Reduction in seizure frequency
Bell shaped curve result between VNS total charge delivered and increased response rate
Increased need for ASMs
Potential post-implantation infection
Seladelpar: Long-Term Safety1
All AEs listed were treatment emergent unless otherwise stated. Safety data collected in RESPONSE were previously reported. Safety data reported were collected in the ASSURE trial only (only during seladelpar exposure) as of January 31, 2025. *One patient initially reported with Grade 3 colitis, likely related to seladelpar, reassessed after the data cutoff as Grade 2, unrelated to seladelpar. †Preferred terms of AEs leading to treatment discontinuation in ASSURE among the continuous seladelpar group included oesophageal varices haemorrhage, adenocarcinoma of the cervix, ascites, hypervolaemia, bipolar I disorder, colon cancer, and hyperbilirubinaemia. ‡Preferred terms of AEs leading to treatment discontinuation in ASSURE in the crossover seladelpar group included lymphoma and myalgia. §Identified using a prespecified search strategy. Liver- and muscle-related AEs reported in ≥2 patients rolling over from RESPONSE shown; all renal-related AEs reported shown. **Liver-related AEs: Crossover SEL (n): ascites (3), AST increased (1), ALT increased (1), hepatic cirrhosis (2), varices oesophageal (1). Continuous SEL (n): ascites (3), AST increased (2), ALT increased (2), hepatic cirrhosis (3), hyperbilirubinaemia (3), varices oesophageal (2), hepatic enzyme increased (2), portal hypertension (2). ††Muscle-related AEs: Crossover SEL (n): myalgia (2). Continuous SEL (n): myalgia (2), muscle spasms (3), musculoskeletal chest pain (3). ‡‡Renal-related AEs: Crossover SEL (n): blood creatinine increased (1), proteinuria (1). Continuous SEL (n): acute kidney injury (1). AE, adverse event; SAE, serious adverse event; SEL, seladelpar.
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1. Levy C et al. Oral presentation 4434. AASLD. 7-11 November, 2025.
Elafibranor: Safety
AE: adverse event; SAE: serious AE.
1. Kowdley KV et al. N Engl J Med. 2024;390(9):795–805 2. Kowdley KV et al. N Engl J Med. 2024;390(9):795–805 (Supplementary Appendix).
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Elafibranor: Long-Term Safety Data
1. Levy C et al. Oral presentation 5016. AASLD, 7-11 November, 2025. 2. Kowdley KV et al. N Engl J Med. 2024;390(9):795−805.
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*Includes events in the OLE as of data cut-off (May 2025) only; †TEAEs occurring in >10% of patients are shown; ‡Cause of death unknown, not related to treatment; §Transaminase elevation was mild in intensity. AESI: adverse event of special interest; TEAE: treatment emergent adverse event.
Jenny Wants to Further Discuss Women's Health Considerations
Jenny expresses the following concern: I want to learn more about my options for 2L therapy and the data surrounding safety and women’s health.
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2L: second-line
Which therapy would be most appropriate in women of child-bearing age?
Seledelpar and elafibranor are equally appropriate
Click here to learn more about PBC 2L therapies and women’s health
1. Electronic Medicines Compendium (emc). Available at: https://www.medicines.org.uk/emc/product/100486/smpc#gref. Last accessed: 16 April 2026.
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2L: second-line; PBC: primary biliary cholangitis.
As a precautionary measure, it is preferable to avoid the use of seladelpar during pregnancy.1
Women’s Health
1. European Medicines Agency. Lyvdelzi [Summary of Product Characteristics]. Available at: https://www.ema.europa.eu/en/documents/product-information/lyvdelzi-epar-product-information_en.pdf. Last accessed: 3 March 2026. 2. European Medicines Agency. Iqirvo [Summary of Product characteristics]. Available at: https://www.ema.europa.eu/en/documents/product-information/iqirvo-epar-product-information_en.pdf. Last accessed: 2 March 2026.
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PBC is female-predominant and affects adults across an age range that includes women of childbearing potential
Clinical Implications and Precautions
There are no or limited amount of pregnancy data (less than 300 pregnancy outcomes) available for seladelpar1 No reproductive toxicity, foetal malformations or adverse embryo-foetal effects were observed in animal studies at clinically relevant exposures1 As a precautionary measure, it is preferable to avoid the use of seladelpar during pregnancy1 Pregnant or breastfeeding patients and patients who are planning to have a baby are advised to consult their doctor1
There is limited amount of data from the use of elafibranor in pregnant women2 In animal studies, elafibranor was associated with congenital malformations and reduced fetal survival when administered during pregnancy and lactation at clinically relevant exposures2 Elafibranor is contraindicated in pregnancy and breastfeeding2
Drug-Drug Interactions with Hormonal Contraceptives with Current 2L Treatment Options
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Hormonal contraceptives are a common concomitant therapy for women of childbearing age with PBC
No specific recommendations for hormonal contraception are made in the SmPC for seladelpar1
Co-administering elafibranor and hormonal contraceptives may lead to contraceptive failure and/or breakthrough bleeding2 Women of childbearing potential must use effective contraception during and up to at least 3 weeks following the final dose of elafibranor2
Drug-Drug Interaction Considerations
Seladelpar + elafibranor are the same
Click here to learn more about PBC 2L therapies and statins
Based on Jenny’s updated prescription of statins, which medication would you recommend?
As the hepatologist reviews Jenny's medical records, he sees she is on a statin.
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Concurrent Use of 2L PBC Treatments and Statins
*Based upon the PK profile of seladelpar and statins; drug interaction studies not conducted for all statins.3 2L: second-line; CPK: creatine phosphokinase; HCP: healthcare provider; PBC: primary biliary cholangitis; PK: pharmacokinetics.
For more information, please refer to the specific product labelling. Clinical decisions may factor in respective pharmacokinetics data and are made at the discretion of the HCP.
1. European Medicines Agency. Lyvdelzi [Summary of Product Characteristics]. Available at: https://www.ema.europa.eu/en/documents/product-information/lyvdelzi-epar-product-information_en.pdf. Last accessed: 3 March 2026. 2. University of Liverpool and TherEx Centre for Experimental Therapeutics. Available at: https://www.hep-druginteractions.org/. Last accessed: 17 December 2025. 3. Electronics medicines compendium (eMC). 2024. Available at: https://www.medicines.org.uk/emc/product/15986/smpc/print. Last accessed: 17 December 2025.
Seladelpar: Seladelpar has no clinically relevant effect on the pharmacokinetics of simvastatin, atorvastatin, or rosuvastatin1 No interactions are expected between seladelpar and statins; concurrent use poses no risk to patients treated with seladelpar*,3 Elafibranor:4 Co-administration of elafibranor and statins can increase the risk of myopathy Patients taking statins concurrently with elafibranor should be monitored for muscle pain, myopathy, and rhabdomyolysis; periodic CPK measurements should be considered
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Treatment Monitoring
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CPK: creatine phosphokinase; PBC: primary biliary cholangitis.
Treatment Goals
1. Supplement for Hirschfield GM et al. N Engl J Med. 2024;390(9):783-94. 2. Hirschfield GM et al. N Engl J Med. 2024;390(9):783-94. 3. Bowlus CL et al. Poster 5031. AASLD, 7-11 November, 2025. 4. Hirschfield GM et al. Oral Presentation 5002. AASLD, 10-14 November, 2023. 5. European Medicines Agency. Lyvdelzi [Summary of Product Characteristics]. Available at: https://www.ema.europa.eu/en/documents/product-information/lyvdelzi-epar-product-information_en.pdf. Last accessed: 3 March 2026. 6. University of Liverpool and TherEx Centre for Experimental Therapeutics. Available at: https://www.hep-druginteractions.org. Last accessed: 23 June 2025.
Addresses pruritus symptoms and related quality of life4
Induces biochemical response and stabilises progression of fibrosis1-3
Demonstrates a tolerable safety profile and ease of use2,4-6
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Hepatolgoy
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1. Supplement for Hirschfield GM et al. N Engl J Med. 2024;390(9):783-94. 2. Hirschfield GM et al. N Engl J Med. 2024;390(9):783-94. 3. Bowlus CL et al. Poster 5031. AASLD, 7-11 November, 2025. 4. Hirschfield G et al. Oral Presentation 5002. AASLD, 10-14 November, 2023. 5. LYVDELZI (seladelpar) Gilead [summary of product characteristics]. County Cork, Ireland: Gilead Sciences Ireland UC; 2025. 6. University of Liverpool and TherEx Centre for Experimental Therapeutics. Available at: https://www.hep-druginteractions.org. Last accessed: 23 June 2025.
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