Narrowing the CGT access gap

Cell therapies hold curative potential, yet far too many patients still can’t access them. In many cases, these treatments aren’t pursued by developers because science is advancing faster than the systems that support it — from reimbursement policies and clinical research infrastructure to manufacturing costs and traditional pharmaceutical business models.

Rare and ultra-rare conditions underscore the urgent need to develop new therapeutic constructs. More than 10,000 rare diseases have been identified;¹ 80%² of these conditions are genetic, and only 5%³ of them have FDA-approved treatments to address them. In short, there are approximately 7,500 identified rare diseases, with patients awaiting solutions from the cell therapy community.

This gap highlights a significant opportunity: to expand the promise of cell therapy beyond its current narrow indications deeper into the rare disease space, and to eventually tackle widespread conditions such as diabetes and neurological disorders. Realizing the promise of cell therapy will require rethinking how we fund research, design reimbursement models, and scale manufacturing to make these therapies viable for smaller patient populations.

Development & commercialization face systemic challenges

Thousands of scientists, engineers and manufacturing professionals worldwide are developing a growing body of advanced therapeutic knowledge; yet patients still wait. Increasingly, the challenge for many of these therapies is less about achieving the next emerging scientific breakthrough and more about organizing scientific efforts, connecting stakeholders, and developing new payment and financial models to advance therapeutic solutions practically, thereby creating real-world impact for an increasing number of patients.

Transforming business models to unlock innovation

Genetic diseases often affect small patient populations and demand tailored approaches, from viral vectors to gene-edited cells, that don’t always align with traditional pharmaceutical business models. Yet this challenge is sparking a wave of creativity across the field. Smaller biotech companies, often backed by mission-driven investors and foundations, are pioneering new funding and partnership models to advance these therapies.

Rather than viewing advanced therapies as commercially untenable, many in the ecosystem are beginning to reimagine what success looks like, measured not only by market size but by impact. As collaborations between large pharma, emerging biotechs and patient advocacy organizations expand, a new framework is emerging: one where innovation, access, and sustainability reinforce each other, and the potential of cell and gene therapies can finally be realized by the patients who need them most.

Inefficiency due to siloed manufacturing knowledge

A culture of proprietary knowledge within the cell therapy manufacturing community creates inefficiency and costs that are higher than necessary. Companies often guard process development and manufacturing know-how as ‘secret sauce,’ even though many processes and unit operations are highly similar across programs. Parallel teams often working in non-overlapping disease areas re-solve identical problems, build redundant facilities, and inhibit the dissemination of practical know-how that could lower costs and speed timelines if shared more freely.

Payer uncertainty

The U.S. medical system, as it evolved over the course of the twentieth century, was constructed for repeat-dose, lifelong therapeutics, and it served many Americans sufficiently for decades. However, as medical and scientific innovation offers the chance to cure genetic diseases, new questions have come into focus, such as the development of new payer constructs that absorb large one-time costs while striving for equitable patient access.

The median continuous tenure for U.S. commercial health insurance plans is approximately three years;⁴ therefore, payers hesitate to shoulder a $2-5 million one-time bill, given that the long-term savings are likely to be enjoyed by other insurance carriers. Despite, in many cases, evidence of longer-term savings, the large upfront costs strain payer budgets and existing reimbursement models. Federal and state-funded health care programs, such as Medicare and Medicaid, likewise struggle with the significant upfront costs.

Beyond new financing and development models that often require nonprofit entities, organizations also need more coordinated access to process development, manufacturing and regulatory guidance to move cell therapies through the pipeline successfully.

Reimagining development & funding models to expand patient access

In this new era of advanced modalities, the status quo is no longer an option — for patients, parents or developers. The curative nature of these therapies yields such a substantial outcome for patients that many innovators are asking more questions about how to approach the development of these novel therapeutics in a more cost-efficient manner, aiming to lower the cost of goods, avoid the pressures of profit generation, and increase patient access.

As discussed, cell therapies are often not a good fit for traditional pharmaceutical or biotech funding models. Costs and risks are too high, payer apprehension risks marketability, and the patient populations for rare diseases are frequently too small to deliver an acceptable return on investment. However, new entities are stepping forward to fill the void.

Patient advocacy groups

Patient advocacy organizations are redefining what it means to accelerate cures. Specifically, disease-specific nonprofits often provide the connective tissue that bridges the gap between patient need and the facilitation of discovery and preclinical development, typically at a university or other research institution. They steward long-term data and advocate with payers for policy, access and affordability. Equally vital, they educate families and clinicians, set ethical guardrails for equity, convene cross-disease collaborations, and pilot nonprofit biotech models for ultra-rare indications. Additionally, they de-risk early science with seed funding, embed the patient voice in study design, and ready trials through their patient networks. They work to help guide therapies to market, although they often struggle in this area and could benefit from efforts to connect early-phase research efforts with manufacturing and regulatory resources.

As cell and gene therapies have expanded from a handful of experimental options to a growing pipeline of commercial and investigational products, the gaps in navigation, access and payer systems have also grown. In response, the Emily Whitehead Foundation, which initially funded early CAR-T research and guided patients to clinical trials, has expanded its mission beyond a single disease to become a disease-agnostic, advanced therapies partner focused on addressing the practical and structural barriers that prevent eligible patients from receiving treatment. Today, the foundation works across cancers and rare diseases to support patients and caregivers throughout their entire journey, while also working with all stakeholders to address the structural barriers that inhibit access and help close the gap between early research, real-world delivery, and what patients actually experience.

Increasingly, organizations like the Emily Whitehead Foundation are building bridges between patients, researchers and manufacturing partners, creating a new paradigm that brings promising therapies to life faster and more efficiently. This shift reflects a powerful idea: when patients and families are treated as collaborators, not bystanders, breakthroughs happen sooner.

Nonprofit research institutions

Nonprofit research institutions also play a vital role by mitigating risks for early-stage programs through grant funding, and their mission-driven focus promotes the democratization of development by encouraging broad licensing and open collaboration, rather than concentrating on profiting from proprietary approaches and technologies.

As explored in a recent conversation with Aedan Coffey, a director at Oregon Health & Science University, nonprofit research hospitals have an exciting role to play. Specifically, they create translational infrastructure for cell therapies through a threefold mission: piloting new treatment models, conducting the right research, and training the next generation of medical professionals. However, as public nonprofit entities, they encounter challenges similar to those faced by many organizations, especially in managing the challenge of balancing multi-million-dollar cell therapy investments against competing population health demands, which necessitate careful decision-making about which advanced therapies to pursue.

During the discussion, Coffey emphasized that, as mission-driven organizations, nonprofit research hospitals are committed to maintaining an ethical compass by continuously evaluating patient outcomes, which supports the effective and equitable allocation of resources. Additionally, to more effectively leverage these insights, public institutions are forming partnerships with the private sector to promote innovation through initiatives like pilot payer negotiation strategies and prioritizing collaborative public-private research projects.

Coordinated public-private collaborations should help focus therapeutic development on meaningful disease areas and allocate R&D dollars across a diverse range of products. This approach will ideally avoid the scenario observed during the recent COVID-19 pandemic, where several hundred potential products with a limited chance of achieving commercial approval entered the clinical trial ecosystem, creating a significant and lasting drag on development investment and expectations.

New government-led reimbursement & regulatory approval models

To experiment with new funding models that expand equitable access to transformative therapies, the CMS Cell and Gene Therapy (CGT) Access Model is a voluntary, multi-year initiative that enables Medicaid programs to utilize CMS-negotiated outcomes-based agreements to cover the costs of expensive CGTs. The CMS (Centers for Medicare & Medicaid Services) sets key terms with manufacturers, including price discounts and outcomes-based rebates.

The initial effort focuses on gene therapies for sickle cell disease, pairing the new payment model with the necessary patient support. States began participating in January 2025, and as of July 2025, 33 states, plus D.C. and Puerto Rico, are participating, representing the vast majority of Medicaid beneficiaries with sickle cell disease. This program is experimenting with new funding models to expand equitable access to transformative therapies while tying payment to real-world outcomes and reducing budget volatility for state Medicaid programs.

Additionally, critical efforts are being made to support increased access and reduced costs from a regulatory perspective. The FDA’s new framework, the ‘plausible mechanism’ pathway unveiled in November 2025, was developed jointly by the CBER and CDER to expedite access to treatments for rare diseases by allowing bespoke therapies to rely on shared ‘platform data.’ Evidence from several consecutive patients, covering mechanism, manufacturing, analytics and safety, can support approvals for closely related, individualized treatments. The approach shifts one-off exceptions to a reproducible framework grounded in mechanism and quality.⁵ It also signals to government and private payers that such therapies rest on credible evidence, thereby opening coverage paths and helping biotechs, academics and nonprofits advance rare disease programs efficiently and ethically.

Connecting cell therapy innovation with development & manufacturing solutions

The network of expertise at a developer’s disposal is commonly the difference between success and failure. Emerging innovators need to consult a process development and manufacturing expert early to chart a viable CMC path, then engage patient advocacy leaders to shape the approach for the target patient population. Including both voices in the room early in the process prevents program-risking errors, aligns trial design with lived experience, and keeps the development plan grounded in what can actually be created, scaled and delivered.

The network of expertise at a developer’s disposal is commonly the difference between success and failure.

This early connective tissue is especially critical in rare diseases, where disease-specific charities often shoulder the burden because no one else will fund the program. Often, these small, mostly virtual groups of researchers and patient advocates need a knowledgeable partner to help define the most expeditious and cost-effective path to both clinical development and commercialization.

A collaborative CDMO partner will help to define the target product profile (TPP) early in development, enabling focused investment to get from concept to clinic. They can then facilitate introductions to key vendors and support functions (e.g., raw materials, specialized testing, pre-clinical safety assessments), saving precious time and avoiding costly mistakes and rework. Additionally, a partner who understands the development paths available for these unique modalities can help assess the elements required for early clinical development (e.g, focus on clinical safety, patient selection, method development, etc.) based on risk assessments, and which elements can be deferred to later stage development (e.g,. operational efficiency, process/method validation, supply chain robustness, etc.).

Also, advanced therapy investors are increasingly asking more questions about CMC strategy and manufacturability during due diligence. Engaging early with a partner to develop and manufacture a unique cell or gene therapy product can help derisk the entire development cycle, including fundraising, newco formation, organizational design, development and GMP manufacturing.

From promise to patients

Cell therapies are transitioning from often impractical concepts to commercial realities, expanding well beyond oncology and rare diseases into diabetes, autoimmune diseases, neurological disorders, and many other conditions. The science is remarkable, but true impact now hinges on the ability to align developers, manufacturers, regulators, providers, payers, and patients to improve efficiencies, lower costs, and expand access.

While the higher initial costs of many cell therapies and the ability to demonstrate durability challenge payers and traditional business models, outcomes-linked contracts, risk-sharing arrangements, and government pilot programs, as well as new regulatory constructs, are redefining how we pay for one-time, high-value care.

Meanwhile, a coalition of patient advocates, disease-specific nonprofits, and nonprofit research hospitals is creating pathways to move from early-phase development to GMP manufacturing and ultimately to patients. Driven by the relentless dedication to ethical patient access, curative cell therapies are becoming a meaningful tool within health care’s therapeutic toolbox. 

*Article commentator: Aedan Coffey, Director, Oregon Health & Science University

References

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2. Rare Disease Facts. (2024). Global Genes.
3. Crooke, S.T. (2021). A call to arms against ultra-rare diseases. Nat. Biotechnol. 39, 671–677.
4. Fang, H., et. al. (2022). Trends in Disenrollment and Reenrollment Within US Commercial Health Insurance Plans, 2006-2018. JAMA Network. 5(2), 220320.
5. Fidler, B. (2025). FDA unveils new regulatory roadmap for bespoke drug therapies. BioPharma Dive.