As the first agent to be approved for primary biliary cholangitis (PBC), ursodeoxycholic acid (UDCA), which launched nearly two decades ago, transformed the treatment of PBC by greatly reducing mortality rates. Intercept’s novel FXR agonist, obeticholic acid (Ocaliva), was approved in the United States and Europe in 2016 and experienced strong initial uptake, primarily among UDCA nonresponders. However, a black box warning was added to Ocaliva in 2018, and a notable subset of PBC patients are still underserved by UDCA. Given the medical advances in the treatment of other liver disorders, there is renewed interest in the development of new PBC agents to address areas of unmet need. Intercept Pharmaceuticals hopes to capitalize on the need for new PBC agents, specifically for patients who do not respond to UDCA, and pipeline agents have the potential to improve on both UDCA and Ocaliva and thus could gain share in what is poised to become a highly competitive market.
QUESTIONS ANSWERED
How effective are the current therapies, UDCA and Intercept Pharmaceuticals’ Ocaliva, in treating PBC?
Given the black box warning it received in 2018, how has the market outlook for Ocaliva in PBC patients changed in the United States and the EU5?
With the availability of UDCA and Ocaliva, what areas of unmet need remain in the treatment of PBC? What improvements can emerging agents offer in the management of PBC?
What clinical endpoints do emerging agents need to meet in order to compete effectively against UDCA and Ocaliva?
CONTENT HIGHLIGHTS
Geographies: United States and EU5.
Primary Research: Six country-specific interviews with thought-leading hepatologists/ gastroenterologistssupported by survey data collected for this study.
Epidemiology: Diagnosed prevalence of primary biliary cholangitis by country, drug-treated cases of primary biliary cholangitis by country.
Forecast: Drug-level sales and patient share of key primary biliary cholangitis therapies in 2018 and 2028.
Regional Sales of Key Therapies to Treat PBC: 2018 and 2028
PBC SWOT Analysis
COVID-19: Areas of Potential Forecast Impact
Drivers and Constraints
What Factors Are Driving Sales in PBC?
What Factors Are Constraining Sales in PBC?
Segment-Specific Trends
UDCA Nonresponders
Alternative Market Scenarios
Alternative Market Scenarios
Alternative Scenarios for the PBC Market Through 2028
Forecast
Forecast Sales of Key Therapies in PBC
Etiology and Pathophysiology
Disease Overview
Etiology
Autoimmune Components of PBC
Infectious Disease Components of PBC
Cytopathic Disease Components of PBC
Pathophysiology
Pathogenesis of PBC
Key Pathways and Drug Targets
Drug Targets in PBC
Epidemiology Overview
Key Findings
Epidemiology Populations
Disease Definition
Methods
Sources Used for Diagnosed Prevalent Cases of PBC
Number of Diagnosed Prevalent Cases of PBC in the Major Pharmaceutical Markets: 2018-2028
Disease Definition
Methods
Sources Used for Diagnosed Incident Cases of PBC
Number of Diagnosed Incident Cases of PBC in the Major Pharmaceutical Markets: 2018-2028
Number of Drug-Treated Prevalent Cases of PBC in the Major Pharmaceutical Markets: 2018-2028 (thousands)
Current Treatment
Key Findings
Diagnosis
Diagnostic Criteria
Treatment Providers and Referral Patterns
Expert Insight: Diagnosis of PBC
Treatment Goals
Key Endpoints Used in Clinical Trials for PBC
Key Current Therapies
Overview
Mechanism of Action of Key Current Drugs or Drug Classes Used for PBC
Current Treatments Used for PBC
Market Events Impacting the Use of Key Current Therapies in PBC
Clinical Trial Outcomes for UDCA
Advantages and Disadvantages of UDCA
Key Results from Select Clinical Trials Investigating UDCA for the Treatment of PBC
Expert Insight: UDCA
Clinical Trial Outcomes for OCA
Clinical Analysis of OCA for the Treatment of PBC
Advantages and Disadvantages of OCA
Expert Insight: OCA
Expert Insight: Fibrates
Fatigue
Pruritus
Sicca Syndrome
Medical Practice
Overview
Treatment Guidelines
PBC Treatment Guidelines
Region-Specific Treatment
Generalized Treatment Decision Tree for PBC
Unmet Need Overview
Current and Future Attainment of Unmet Needs in PBC
Top Unmet Needs in PBCu2014Current and Future Attainment
Expert Insight: Unmet Need in PBC
Emerging Therapies Overview
Key Findings
Pipeline Trends for PBC
Key Emerging Therapies
Key Therapies in Development for PBC
Estimated Launch Dates of Key Emerging Therapies for the Treatment of PBC
Seladelpar Profile
Key Ongoing Clinical Trials of Seladelpar in the Treatment of PBC
Analysis of the Clinical Development Program for Seladelpar
Expert Insight: Seladelpar
Expectations for Launch and Sales Opportunity of Seladelpar in PBC
NGM-282 Profile
Analysis of the Clinical Development Program for NGM-282
Expectations for Launch and Sales Opportunity of NGM-282 in PBC
FXR Agonists Profile
Key Ongoing Clinical Trials of FXR Agonists in the Treatment of PBC
Analysis of the Clinical Development Programs for FXR Agonists
Expectations for Launch and Sales Opportunity of FXR Agonists in PBC
Linerixibat Profile
Key Ongoing Clinical Trials of Linerixibat in the Treatment of PBC
Analysis of the Clinical Development Program for Linerixibat
Expert Insight: Linerixibat
Expectations for Launch and Sales Opportunity of Linerixibat in PBC
Elafibranor Profile
Analysis of the Clinical Development Program for Elafibranor
Expert Insight: Elafibranor
Expectations for Launch and Sales Opportunity of Elafibranor in PBC
Key Results from Select Clinical Trials Investigating Setanaxib for the Treatment of PBC
Analysis of the Clinical Development Program for Setanaxib
Expert Insight: Setanaxib
Expectations for Launch and Sales Opportunity of Setanaxib in PBC
Select Phase II Compounds in Development for PBC
Patient Registries
Patient Registries for PBC
Prominent PBC Patient Organizations
Orphan Drug Designation
Access & Reimbursement Overview
Region-Specific Reimbursement Practices
General Reimbursement Environment: United States
General Reimbursement Environment: EU5
Appendix
Key Abbreviations Related to PBC
Brands, Marketers, and Generic Availability of Key Therapies for PBC, by Market
Experts Interviewed
PBC Bibliography
Kanika Ujla
Abey John, M.P.H., is an epidemiologist at DRG, part of Clarivate. Prior to joining DRG, he worked with Jhpiego (an affiliate of Johns Hopkins Medical University) in implementing family planning health programs in India in collaboration with the government of India. He also has worked at the grassroots level as a health team manager to help the rural population living in the foothills of the Himalayas. He holds a master’s degree in public health.