Regenerative Medicine: Unlocking Patient Access and Commercial Potential

Cover
Half Title
Series
Title
Copyright
Contents
Preface
Author Biographies
List of Abbreviations
Chapter 1 Regulation of RMs in Globally
1.1 Regulation of RMs in Each Country
1.1.1 European Union (EU)
1.1.1.1 Regulation on Advanced Therapy Medicinal Products
1.1.1.2 Market Authorization of ATMPs
1.1.1.3 ATMPs Approved in the EU
1.1.2 United States
1.1.2.1 Regulation on Cell and Gene Therapies
1.1.2.2 Expedited Pathway to Accelerate the Market Authorization
1.1.2.3 Cell and Gene Therapies Approved in the USA
1.1.3 Japan
1.1.3.1 New Released Pharmaceutical and Medical Device Act
1.1.3.2 Time-Limited and Conditional Market Authorization
1.1.3.3 Act on the Safety of Regenerative Medicine
1.1.3.4 Regenerative Medicine Approved in Japan
1.1.4 Australia
1.1.4.1 Australian Regulatory Guidelines for Biologicals
1.1.4.2 Classification Before Inclusion in the ARTG
1.1.4.3 Cell and Gene Therapies Approved in Australia
1.1.5 Canada
1.1.5.1 Regulations on Biologicals
1.1.5.2 Strategies to Facilitate Market Authorization
1.1.5.3 Cell and Gene Therapies Approved in Canada
1.1.6 South Korea
1.1.6.1 Before August 2020: Pharmaceutical Affairs Act
1.1.6.2 After August 2020: Advanced Regenerative Medicine Act
1.1.6.3 Cell and Gene Therapies Approved in South Korea
1.1.7 China
1.1.7.1 Regulation of Biological Products
1.1.7.2 Cell and Gene Therapies Approved in China
1.1.8 Singapore
1.1.8.1 Regulation of Cell, Tissue, and Gene Therapy Products
1.1.8.2 Gene Therapies Approved in Singapore
1.1.9 India
1.1.9.1 Regulation of Cell, Tissue, and Gene Therapy Products
1.1.9.2 Cell and Gene Therapies Approved in India
1.1.10 New Zealand
1.2 Comparisons Between Countries
1.2.1 International Classification and Definitions of RMs
1.2.2 RM Legislation and Frameworks
1.2.3 International RM Market Authorization Procedures
1.2.4 Regulatory Assessment Considerations for RMs
1.2.5 Acceptance of Alternative Evidence Generation
1.2.6 Expedited MA Assessment Programs for RMs
1.2.7 Accelerated Approval Programs for RMs
1.2.8 Post-market Requirements for RMs Approved
1.2.9 RMs Sponsor Incentives
1.3 Challenges and Recommendations
1.3.1 Discrepancies Between RM Regulatory Requirements
1.3.2 The Significance of Post-Market Evidence Generation
1.3.2.1 Rising Concerns Around Expedited Approval Programs
1.3.2.2 Challenges in Post-Market Evidence Collection
1.3.3 Prospects and Recommendations
1.3.3.1 International Harmonization for RM Regulations
1.3.3.2 More Clarification and Transparency in the Regulatory Activities
1.3.3.3 Strategies to Ensure That Post-Market Scientific Obligations Are Fulfilled
1.3.3.4 Patient Registry Platforms for Rare Diseases
1.4 Conclusion
Chapter 2 Health Technology Assessment of RMs
2.1 Country-Specific HTA Decisions for Individual Products
2.1.1 Glybera (Alipogene Tiparvovec)
2.1.2 Kymriah (Tisagenlecleucel)
2.1.3 Luxturna (Voretigene Neparvovec)
2.1.4 Imlygic (Talimogene Laherparepvec)
2.1.5 Strimvelis
2.1.6 Yescarta (Axicabtagene Ciloleucel)
2.1.7 Zynteglo (Betibeglogene Autotemcel)
2.1.8 Libmeldy (Atidarsagene Autotemcel)
2.1.9 Zolgensma (Onasemnogene Abeparvovec)
2.1.10 Tecartus (Brexucabtagene Autoleucel)
2.2 Summary of Study Limitations
2.2.1 Comparative Studies
2.2.2 Study Populations
2.2.3 Study Endpoints
2.2.4 Statistical Analysis
2.2.5 Confounding Factors
2.2.6 Data Transferability and Generalizability
2.2.7 Comparison of Indirect Treatments
2.3 Discussion and Recommendations
2.3.1 Discrepancy in the Health Technology Assessment
2.3.2 Value Determination
2.3.3 Reimbursement and Affordability Strategies
2.3.4 Recommendations for Clinical Trials for RMs
2.3.4.1 Study Populations
2.3.4.2 Comparators
2.3.4.3 Study Endpoints
2.3.4.4 Analysis Methods
2.3.4.5 Indirect Comparison
Chapter 3 Challenges for Market Access of RMs
3.1 Challenges in the Health Technology Assessment
3.1.1 Uncertainties in the Clinical Evidence
3.2 Challenges in Economic Analysis
3.2.1 Challenges in Value Assessment
3.3 Challenges in Pricing, Reimbursement, and Affordability
3.3.1 Controversy Surrounding the High Price of RMs
3.3.2 High Up-Front Costs Threaten the Existing Payment System
3.3.2.1 Unique Challenges Due to the One-Off Treatment Nature
3.3.2.2 Downstream Costs to Be Considered
3.3.2.3 Free-Rider Issues
3.3.2.4 Consequence of Insufficient Coverage of RMs
3.4 Challenges in Innovative Payment Strategies
3.4.1 Outcome-Based Payment
3.4.2 Annuity Payment/Installment Payment
3.5 Discussion and Recommendations
3.5.1 Summary of the Study Findings
3.5.2 Future Recommendations
3.5.1.1 Improve the Quality of Clinical Evidence
3.5.1.2 Think Economically Early in Development
3.5.1.3 Implications for Decision-Markers
3.6 Conclusion
Chapter 4 Impact of COVID-19 on the RMs Industry
4.1 Tremendous Disruptions for All Activities
4.1.1 Supply Chain and Manufacturing
4.1.2 Clinical Trials
4.1.3 Delivering Therapies to Patients
4.1.4 Small Businesses
4.1.5 Regulatory Activities
4.1.6 Health Technology Assessment
4.2 Progress Made During the Pandemic
4.2.1 New Treatment Opportunities
4.2.2 Financing Raised
4.2.3 Regulation Milestones
4.2.3.1 Products Approved During the Pandemic
4.2.3.2 Initiatives to Facilitate the Approval of Promising Products
4.3 Conclusion
Chapter 5 Partnerships to Expedite Successful Market Access for RMs
5.1 Overall Description of the Partnership for RMs
5.2 Key Players in Partnership Agreements
5.3 Discussion
5.3.1 Overall Description
5.3.2 Types of Partnership Agreements
5.3.3 Future Trends and Strategies
5.4 Case Analyses: Partnerships for Approved RMs
5.4.1 RMs Commercialized on the Market
5.4.1.1 Alofisel
5.4.1.2 Imlygic
5.4.1.3 Kymriah
5.4.1.4 Luxturna
5.4.1.5 Strimvelis
5.4.1.6 Yescarta
5.4.1.7 Zolgensma
5.4.1.8 Zynteglo
5.4.2 RMs Withdrawn from the Market
5.4.2.1 Glybera
5.4.2.2 Zalmoxis
5.4.2.3 ChondroCelect
5.4.3 Summary
5.5 Conclusion
Chapter 6 Business Models and Commercial Considerations for Gene and Cell Therapies
6.1 Forecast of the Cell and Gene Therapy Market
6.2 Increasing Investment Will Bring Fast-Growing Revenue
6.2.1 Cell and Gene Therapy Market Forecast for the United States
6.2.2 Cell and Gene Therapy Market Forecast for Europe
6.2.3 Cell and Gene Therapy Market Forecast for China
6.3 More Challenges in Manufacturing and Delivery
6.3.1 Challenges in Manufacturing
6.3.2 Challenges in Patient Selection
6.3.3 Challenges in Logistics and Product Delivery
6.3.4 Challenges in Manufacturing Allogeneic Therapies
6.4 Why Cell and Gene Therapies Require a Unique Business Model
6.4.1 Collaboration to Navigate Manufacturing Challenges
6.4.2 Limited Role of Regional Affiliates
6.4.3 Disruptions to the Traditional Process of Administration and Monitoring
6.4.4 The Time of Approval Is Critical to Secure Market Success
6.4.5 Different Business Strategies for Cell and Gene Therapies
6.5 Partnerships to Drive the CGT Landscape Progression
6.5.1 The Advantage of Partnerships
6.5.2 Key Cell and Gene Therapy Participants
6.6 New Payment Models Are Needed for Such Innovative and Costly Therapies
6.6.1 The Efficacy and Safety of CGTS Are Not Fully Understood
6.6.2 Different Value Profiles for Different Patient Populations
6.6.3 High Prices of Cell and Gene Therapies Raised Payment Barriers
6.6.4 Innovative Payment Strategies to Address Payment Challenges
6.6.5 Obstacles in Implementing Innovative Payment Strategies
6.7 Conclusions
Chapter 7 Summary of Recommendations and Perspectives for Future Research
7.1 Summary of Key Findings
7.2 Recommendations for Manufacturers
7.2.1 Partnerships to Streamline the Market Access of RMs
7.2.2 Strategies to Strengthen the Quality of Clinical Evidence
7.2.3 Active Engagements with Other Stakeholders
7.3 Implications for Future Research Efforts
7.3.1 From the Perspective of Market Authorization
7.3.2 From the Perspective of HTA and Affordability
7.4 References
Index