Advanced Therapies Week 2025: Two Sides of the CGT Coin, Development and the Patient Journey

The session titled “Heads or Tails: Two Sides of the Cell and Gene Therapy Coin, Advanced Therapeutic Development and the Patient Journey” presents a comprehensive dialogue between industry experts and a patient advocate, exploring the multifaceted landscape of cell and gene therapy. The discussion delves into the scientific, commercial, regulatory, manufacturing, and patient-centric challenges and opportunities in the space, with a focus on translating cutting-edge science into viable, accessible therapies. It highlights the tension between innovation and practical implementation, the complexities of funding, regulatory harmonization, manufacturing scalability, and the critical role of patient advocacy in shaping the future of rare disease treatments.

The panel begins by addressing the overarching challenge in cell and gene therapy, demonstrating return on investment to attract sustained capital and commercial confidence amid a rapidly growing pipeline but a relatively small end market. Compared to antibodies, gene therapy pipelines have surged without a proportional market growth, underscoring the pressure to prove commercial viability promptly due to looming patent cliffs in other pharmaceutical areas. Access to capital remains a persistent hurdle, compounded by the need to justify investments through demonstrable value, particularly in a capital-constrained environment. Developers must strategically select indications where gene therapies provide unique advantages and plan meticulously for launch readiness, cost of goods reduction, and payer reimbursement.

The discussion underscores the manufacturing challenges, such as high costs, scalability issues, and the debate between centralized versus decentralized production models. Automation and closed systems are deemed essential for reducing costs and risks but remain capital intensive and biologically complex to implement fully. The panelists emphasize the importance of balancing engineering solutions with unresolved biological complexities, suggesting that full automation may be premature until biological understanding matures.

Regulatory evolution is described as a positive yet cautious journey, with agencies providing more guidance and frameworks, for example potency guidance and advanced manufacturing technology designations, but still facing challenges around harmonization across jurisdictions and integration of health economics into approval processes. The regulatory bodies are portrayed as transitioning from enforcers to partners, though legislative and safety priorities can complicate harmonization efforts.

The patient perspective is vividly brought to life through Brett Kopelan, a father and advocate whose daughter suffers from epidermolysis bullosa, a rare and severe genetic skin disorder. Brett shares his personal journey from clinical psychologist to rare disease advocate and nonprofit executive, emphasizing the critical role of patient advocacy in driving research, regulatory engagement, payer discussions, and clinical trial enrollment. He highlights the complexities of pricing versus value, especially in ultra-rare diseases with small patient populations and high standard-of-care costs. Brett stresses the need for long-term economic models, a 7 to 10 year horizon, to capture the true cost-benefit of therapies and expresses concern about the current constrained investment climate. He also shares insights on the challenges and opportunities in patient engagement, clinical trial participation, and data collection via registries to accelerate development.

The session closes with an interactive Q&A, addressing topics such as clinical trial recruitment barriers, the need for better data harmonization, regulatory flexibility, and the evolving role of patient advocacy. Overall, the dialogue portrays the cell and gene therapy field at a critical inflection point, balancing extraordinary scientific promise with the pragmatic demands of commercialization, manufacturing, regulatory approval, and patient access.

Highlights

• Demonstrating return on investment is the biggest challenge in cell and gene therapy to sustain funding and commercial interest.
• Biological complexity still limits full automation in manufacturing, requiring harmonized engineering and biology solutions.
• Regulatory agencies have evolved into collaborative partners, providing guidance but facing challenges in global harmonization and health economics integration.
• Centralized versus decentralized manufacturing remains a debated continuum, with control, consistency, and cost as pivotal factors.
• Patient advocacy plays a crucial role in shaping clinical development, regulatory pathways, and payer negotiations, especially in rare diseases.
• Long-term economic models are essential to justify the value of costly therapies in rare and ultra-rare diseases.
• Current capital constraints and investment challenges threaten the pace of innovation and therapy commercialization.

Key Insights

• ROI and Market Maturity Gap: The cell and gene therapy market faces a paradox, the pipeline has rapidly expanded to over 600 assets, yet the market size remains under five billion dollars, smaller than antibody therapeutics at a similar pipeline size years ago. This mismatch pressures developers and investors to focus on near-term commercial viability and reimbursement strategies, especially with major blockbuster drugs losing patent exclusivity soon. The insight emphasizes that innovation alone is insufficient without clear, actionable paths to market adoption and payer acceptance.
• Biological Unknowns Impede Automation: While manufacturing automation is touted as a cost-reduction strategy, the field is hindered by incomplete understanding of biological processes. The intricate interplay of cellular responses makes it difficult to establish robust engineering solutions without risking process variability. This necessitates a phased approach, first resolving biological complexities before fully embracing automation, rather than rushing into costly and potentially premature engineering investments.
• Regulatory Evolution and Harmonization Challenges: Regulatory bodies have progressed from ad hoc guidance to structured frameworks, including potency standards and advanced manufacturing designations, which provide clearer expectations and accelerated pathways. However, legislative and jurisdictional differences limit full harmonization, with regulators balancing patient safety against rapid access to transformative therapies. The insight highlights a critical tension, regulators must maintain control and responsibility within their jurisdictions while facilitating global data sharing and approval efficiencies to benefit patients worldwide.
• Manufacturing Models Must Align With Therapy Type and Market Needs: The panel debates centralized versus decentralized manufacturing, noting that the best approach depends on therapy characteristics, for example autologous versus allogeneic, and logistical considerations like vein-to-vein time. Decentralized models may reduce time and certain costs but introduce complexity in quality control and supply chain management. Centralized models benefit from economies of scale and consistent regulatory compliance but may struggle with scalability and patient access speed. This insight underscores the necessity to tailor manufacturing strategies to the specific therapeutic and commercial context rather than seeking one-size-fits-all solutions.
• Patient Advocacy as a Critical Industry Partner: Brett Kopelan’s narrative exemplifies how patient advocates can drive progress by influencing clinical trial design, regulatory discussions, payer negotiations, and legislative advocacy. Their involvement accelerates development timelines, for example protocol harmonization, educates stakeholders about disease burden and patient risk tolerance, and ensures patient-centric endpoints are prioritized. This insight elevates patient advocacy from a peripheral role to a central pillar of successful advanced therapy development.
• Economic Models Must Reflect Long-Term Value and Disease Burden: Rare and ultra-rare diseases often incur immense ongoing healthcare costs, for example one point three million dollars per year for EB care, yet payers struggle with short-term budget impacts and high therapy prices. Constructing economic models with seven to ten year horizons is essential to capture downstream savings and quality of life improvements. This insight stresses that without such models, payers may undervalue transformative therapies, leading to access barriers and underinvestment.
• Capital Constraints Threaten Innovation Trajectory: Despite scientific advances, the field faces a capital drought, particularly in early and mid-stage funding rounds. Investors demand clear value inflection points like successful product launches or partnerships, but the slow commercialization pace and reimbursement uncertainties create a challenging environment. This insight signals a need for improved communication of realistic success metrics and value propositions to attract and sustain investment.

Extended Analysis
The session elucidates the tightrope walk facing cell and gene therapy stakeholders, balancing the extraordinary scientific potential to cure or dramatically improve devastating diseases against the practical realities of manufacturing, funding, regulation, and market access. The discussion reveals that each facet is intertwined, manufacturing advances depend on biological insights, regulatory progress requires patient and payer engagement, investment hinges on credible value demonstration, and patient advocacy is vital to bridge gaps and accelerate adoption.

The comparison to the antibody therapeutic market underscores the infancy of gene therapy commercialization. While pipelines grow explosively, the market has not yet matured commensurately, resulting in pressure to accelerate product launches and payer reimbursement. The panelists caution against rushing to market without readiness, advocating for strategic indication selection and thoughtful launch planning to optimize outcomes and avoid scenarios where promise fails to translate into sales.

Manufacturing challenges are particularly acute, with cost of goods remaining high due to labor intensity, lack of scalability, and the complexity of autologous products. Automation is recognized as a long-term solution but is currently limited by biological uncertainties and capital costs. The debate on centralized versus decentralized manufacturing models reveals no silver bullet, rather, a continuum exists, and decisions must weigh control, consistency, costs, and patient access speed. Regulatory frameworks have evolved but remain fragmented globally. The interplay between regulatory approval, health technology assessment, and reimbursement is a critical frontier, with patient advocacy groups increasingly playing a pivotal role in shaping these dynamics.

Brett Kopelan’s personal and professional journey provides a powerful lens to understand the human impact behind the science. His experience navigating rare disease care, advocating for regulatory and legislative reforms, and confronting payer challenges underscores the vital importance of integrating patient voices throughout the therapy development lifecycle. His emphasis on long-term economic modeling and the difficulty of investment in ultra-rare diseases highlights systemic issues that must be addressed to sustain innovation.

The session ends on a cautiously optimistic note, with hope pinned on more successful commercial launches, improved capital flow, and enhanced collaboration among developers, regulators, payers, and patients. However, it is clear that the path forward requires coordinated efforts to address biological unknowns, manufacturing challenges, regulatory complexities, market access issues, and patient engagement to unlock the full potential of cell and gene therapies.

Speakers:

• Alan Smith – Executive Director, Operations Excellence, Biomanufacturing, Charles River Laboratories (Chair)
• Jeff Holder – Managing Director, L.E.K. Consulting
• Joe Senesac – Acting CTO, NKILT Therapeutics
• Robert Allen – Managing Partner, Dark Horse Consulting Group
• Phil Vanek – Chief Commercialization Officer, ISCT
• Matthew Hewitt – Vice President and Technical Officer, Cell and Gene Therapy, Charles River Laboratories
• Brett Kopelan – Executive Director, debra of America

Conclusion
This Advanced Therapies Week 2025 session offers a multifaceted look at how development realities intersect with the patient journey. It emphasizes coordinated progress across biology, engineering, regulation, economics, and advocacy to convert scientific promise into accessible treatments.