Why Cell and Gene Therapy Keeps Stalling at the Bedside

Cell and gene therapies (CGTs) represent one of the most significant therapeutic breakthroughs in modern medicine. Yet despite remarkable clinical progress, most eligible patients still never receive these therapies. Today, only an estimated 20-30% of patients who are clinically eligible for treatments such as CAR-T ultimately access them¹.

The bottleneck is no longer science; it is infrastructure. The healthcare system was optimized to deliver chronic, repeatable therapies, not highly personalized, operationally complex, multi-million-dollar treatments that require coordination across manufacturers, providers, logistics networks, and payers. CGT is evolving from a scientific problem into an operational scaling problem.

Despite these challenges, the market may be nearing peak complexity. With coordinated investment across manufacturers, providers, innovators, and payers, the ecosystem can mature in a way that enables broader patient access.  

At LRVHealth, we have spent years examining how this market will evolve and what capabilities will be required to catalyze its next phase. From an investment perspective, we are focused on opportunities that could expand access to these therapies across the ecosystem — whether through payment innovation, operational and care delivery infrastructure, or community sites of care required to make these therapies viable outside of a handful of elite centers.  

Where the System Breaks Down Today

Bottlenecks persist across the CGT ecosystem, collectively creating a “cold start” problem that is throttling market growth. Limited provider capacity constrains patient access, while low patient volumes make it difficult for health systems to justify investment in new capabilities. Without this investment, the market struggles to scale.

While much attention has been paid to manufacturing constraints, supply chain fragility, and reimbursement mechanics, far less focus has been placed on care delivery readiness. Without addressing this gap, access will remain fundamentally limited.

Delivering CGTs places extraordinary clinical and administrative demands on the care delivery system. Using CAR-T as an example, delivery requires complex coordination across the entire care journey. Before treatment begins, providers must navigate  referral, authorization, and eligibility workflows that are fragmented and bespoke. The treatment phase itself is even more complex. CAR-T delivery requires tightly coordinated “vein-to-vein” orchestration across providers, manufacturers, logistics partners, and payers. Delays or breakdowns at any point — from authorization to manufacturing to post-treatment monitoring — can derail therapy altogether. And for providers that bear upfront drug costs, this can result in significant financial losses. The burden continues after treatment. Patients often require intensive monitoring, prolonged surveillance, and multi-year outcomes reporting.

Even the most sophisticated academic medical centers struggle under this load. Specialized centers are oversubscribed, while community practices and health systems, where most oncology care is actually delivered are effectively locked out. Many patients must travel significant distances for care or never access treatment at all. Many providers remain hesitant to refer patients into a process that is burdensome. The result is a severe access constraint that has materially limited market growth.  

Breaking Down the CGT Category

One of the challenges in discussing cell and gene therapies (CGTs) is that the category includes several very different treatment modalities with distinct operational, financial, and care delivery requirements. Grouping them together can obscure the unique challenges each creates for the healthcare system.

Gene therapies

Gene therapies deliver genetic material directly into the patient’s body through a one-time infusion or injection designed to modify or replace a disease-causing gene. Examples include Zolgensma for spinal muscular atrophy and Hemgenix for hemophilia B.

Because these therapies are manufactured in larger batches and administered across many patients, they function more like ultra-high-cost biologics than bespoke procedures. Their primary access challenges include:

• Financing: Extremely high upfront costs tied to their positioning as potentially curative, single-dose therapies (e.g., Zolgensma launched at approximately $2.1M per dose).  

• Durability uncertainty: Limited long-term data creates uncertainty around the durability of outcomes, with payer and outcomes-based reimbursement models still evolving.

• Patient identification: Many therapies target rare diseases, where diagnosis, identification, and referral of eligible patients can be long and complex.

Cell Therapies

In contrast, cell therapies involve collecting and modifying immune or other cells outside the body before reinfusing them into the patient to better recognize and treat disease.

Unlike gene therapies, the primary challenges are operational and infrastructure-related:

• Operational logistics: These therapies are highly personalized and require complex processes to collect, manufacture, transport, store, and return patient-specific cells.  

• Site readiness: Treatment is limited to specialized centers with the clinical infrastructure, workforce, and operational expertise needed to administer these therapies safely. Access therefore depends heavily on referral networks, site capacity, and patient’s ability to travel to qualified treatment centers.

Cell-Based Gene Therapies

Cell-based gene therapies (also called ex vivo gene therapies) combine elements of both categories. In these therapies, cells are collected from the patient, genetically modified outside the body, and then reinfused. Examples include CAR-T therapies such as Kymriah, as well as gene-modified stem cell therapies like Lyfgenia and Casgevy for sickle cell disease.

These therapies sit at the highest-complexity end of the CGT spectrum because they combine the manufacturing and logistics complexity of cell therapy with the financing and durability challenges of gene therapy. Each dose is custom manufactured for a single patient, creating fragile supply chains, limited throughput, and significant operational burden for providers and payers.

While all CGTs face access and reimbursement challenges, the healthcare system readiness gap is most acute for cell-based therapies, where clinical innovation is advancing faster than the infrastructure needed to deliver them at scale.

‍Why Lean in Now

Despite these constraints, the market may be reaching an inflection point:

• Larger populations: Increasingly, therapies are targeting diseases with larger patient populations, including solid tumor oncology indications, as well as going beyond oncology to neurology and autoimmune conditions rather than exclusively rare diseases.

• Allogeneic/in-vivo innovation: Biopharma manufacturers continue to invest in alternatives to early generations of autologous cell therapies, including in-vivo and allogeneic CAR-T, “off-the-shelf” approaches that seek step-function improvements in scalability and manufacturing simplicity.  

• Earlier lines of treatment: Cell therapies are moving earlier in the treatment paradigm in hematologic malignancies, from third- and fourth-line to second- and maybe even first‑line treatments  

• Easing requirements: The removal of REMS (Risk Evaluation and Mitigation Strategy) requirements and the reduction in required monitoring periods for certain existing CAR-T products has also begun to ease some of the post-treatment burden

• Outpatient migration: Sites of care are beginning to shift, with the potential to broaden access points for these therapies. Manufacturers are exploring how to expand site-of-care networks beyond academic centers of excellence. Community providers are also increasingly exploring participation in CGT delivery.

As eligible populations expand, risk and monitoring requirements improve, and technological advances reduce manufacturing complexity and enable greater scale, stakeholders across the ecosystem increasingly have economic and strategic incentives to invest in the capabilities required to support access.  

‍A Maturing Innovation Landscape

More importantly, a new orchestration layer is emerging around CGT delivery — much like specialty pharmacy evolved alongside biologics. Different types of innovation are emerging:

• Enablement platforms are emerging to help providers orchestrate workflows, reimbursement, manufacturing coordination, and longitudinal monitoring.

• Center‑of‑excellence networks and high-cost therapy benefit management providers are acting as market makers, aggregating demand across payers, coordinating access to certified treatment centers, improving referral pathways for patients while helping manufacturers ensure geographic coverage and program quality.

• Ambulatory enablement models are helping CAR-T move into outpatient or community settings. Purpose-built alternative sites of care, including specialty infusion and oncology centers, are emerging to safely administer advanced therapies outside traditional inpatient environments, thus reducing cost and expanding geographic reach. Over time, these sites may also support select ex vivo therapies as protocols and monitoring requirements become more standardized.

• Shared infrastructure: As development accelerates for future cell therapy applications in auto-immune and other therapeutic areas, providers and manufacturers have begun to explore shared cell therapy service models which could emerge from existing oncology infrastructure.

Taken together, these developments suggest that cell and gene therapies may become a much larger therapeutic category over the medium term, and that the care delivery ecosystem needs to prepare accordingly.

What This Means for Stakeholders

For quaternary centers, particularly academic medical centers and children’s hospitals, the strategic question is whether CGT is core to their long-term clinical, research, and enterprise strategy. For many systems, CGT is becoming a driver of specialty differentiation, referral growth, and research relevance. There is strategic risk in not participating, particularly in rare disease, oncology, and other specialty service lines where CGTs may increasingly shape patient flow and competitive positioning. The challenge is determining how aggressively to scale these programs while balancing mission, operational complexity, capital requirements, and financial sustainability. This creates opportunities for new partnership models — including working with innovators to expand capabilities with lower upfront capital risk, partnering with community hospitals to strengthen referral networks and develop a continuum of care, or collaborating with like-minded institutions on shared clinical and manufacturing infrastructure.

For community hospitals and ambulatory providers, the opportunity may not be to become full CGT administration sites, but to participate in the broader care continuum. This could include diagnostics, patient identification, pre-treatment workup, longitudinal monitoring, and post-treatment follow-up delivered closer to home in partnership with quaternary centers. As CGT volumes grow, organizations that remain outside these networks risk increased patient leakage and reduced relevance in certain high-acuity service lines like oncology and neurology.

For life sciences and pharmaceutical companies, the focus must shift toward partnering on site readiness, supporting decentralized delivery models while maintaining safety, training, and regulatory compliance, and potentially rethinking pricing structures — such as offering discounts in exchange for access to larger patient populations.

For payers, CGTs challenge traditional medical benefit economics because they concentrate years of expected value into a single upfront event. This creates pressure to develop new reimbursement, risk-sharing, and network strategies while balancing affordability with access.

What We’re Looking for – and What We’re Still Working through

Many questions remain on how the market will evolve: How far can delivery decentralize without compromising safety? Will innovations such as in vivo, allogeneic, or point-of-care manufacturing meaningfully reduce complexity? Who will own the orchestration layer across patients, providers, manufacturers, and payers? And will health systems and oncology clinics build these capabilities, share them, or outsource them?

What is becoming increasingly clear is that CGT is not just a new therapeutic category but a new healthcare infrastructure category. Realizing the full promise of CGTs will require a scalable operational layer spanning provider workflows, logistics coordination, reimbursement models, workforce enablement, and longitudinal patient management.

¹https://www.kucancercenter.org/news-room/news/2025/07/expanding-access-to-car-t-cell-therapy (Gandhi MD et al., Blood Advances, 2022)

‍