Cell and gene therapies (CGTs) can now cure diseases that were untreatable a decade ago, often with a single dose. Yet most eligible patients – even those in rich countries like the United States – will never receive them. In many cases, the science is already in place. However, high list prices and healthcare systems ill-equipped to assess the value of CGTs mean that access is not, making new reimbursement and manufacturing models a sector priority.
Science is Settled: Cost is the Problem
“Licensed cell therapy products are already being used extensively in oncology, particularly in lymphomas, leukemias, and myeloma,” lays out Dr David J Rawlings, director of the Center for Immunity and Immunotherapies at the Seattle Children’s Research Institute. His lab engineers cell therapies to treat autoimmune disease, cancer, and genetic disorders.
With more than 3,200 cell and gene therapy trials now underway worldwide, the field is long past proof of concept. “But the defining challenge of this moment is not efficacy; it is cost,” continues Rawlings. “Moving these therapies into earlier lines of treatment requires convincing payers that the upfront cost is justified by the long-term reduction in disease burden and treatment expenditure. That argument becomes compelling only when the durability of benefit is clearly established, and establishing that takes time and real-world evidence that the field is still accumulating.”
Industry executives – with a commercial as well as patient motivation in expanding access to these therapies – are singing from the same hymn sheet.
“CAR-T is no longer an emerging or experimental technology,” notes Brian Heath, SVP and head of global commercial at Kite Pharma (a Gilead company), which makes autologous CAR-T therapies for blood cancers.
“Kite Pharma alone has now treated more than 34,000 patients globally, which reflects both the maturity of the platform and the meaningful outcomes these therapies are already delivering,” adds Heath. “The more important question is why such a large proportion of clinically eligible patients still never receive treatment.”
“There have been a number of approved gene therapies that were discontinued simply because the sticker price made them unaffordable,” laments Thomas Madden, CEO of Acuitas Therapeutics. “It does not make sense to continue investing in this technology without ensuring there is a clear pathway to patient access.”
Unlike the standard global industry story – whereby Europe lags behind the US on access to cutting-edge therapies – Heath explains that, for CGTs, the reverse is often true. “More patients are reaching CAR-T therapy in certain European markets than in the US, even though the underlying science, manufacturing process, turnaround times, and clinical outcomes are fundamentally the same,” he notes. “That suggests the challenge is not the therapy itself, but rather the way healthcare systems integrate and deliver innovation.”
Reimbursement: Paying for a Cure
The core mismatch is structural. The US system was built to pay for chronic treatments, a steady stream of prescriptions filled over years, not for a single infusion that costs millions upfront and pays itself back only over a lifetime. “Cell and gene therapies do not fit neatly into healthcare systems that were largely designed around chronic treatment models rather than potentially transformative one-time therapies,” notes Heath. “Providers need to feel confident that reimbursement will be predictable and sustainable before they can meaningfully scale access.”
Sickle cell disease (SCD) shows the problem in sharp relief. Two new gene therapies – one from Vertex Pharmaceuticals and another from Genetix Biotherapeutics (formerly bluebird bio) can essentially cure the disease with a single treatment, but they cost between two and three million dollars per patient. For a disease which disproportionately affects Black and lower-income Americans and with 50 percent of the US patient population on Medicaid, that is a problem. As Medicaid – the US government’s healthcare programme for low-income Americans – is run state-by-state, no individual state was willing to gamble millions on a treatment that may or may not work in the long-term.
One solution, launched in 2024, is the Centers for Medicare & Medicaid Services (CMS)’ CGT Access Model. For the first time, this introduces outcomes-based payments for costly one-time treatments to the US system, starting with SCD gene therapies, but with the potential to be expanded to other indications. Under the Model, if a treatment delivers the promised benefit, the manufacturer gets paid in full and, if it does not, the manufacturer must give money back in rebates. So far 33 states, as well as Washington DC and Puerto Rico, have opted in.
For Genetix CEO David Meek, despite the issue of returning funds if clinical outcomes are not achieved, the Model is a win-win and “a genuine game changer for access, creating a much more efficient pathway compared to negotiating reimbursement state by state.” He adds that “today, more than 90 percent of SCD patients in the US have meaningful access to our genetic therapy.” Genetix, with a portfolio of three FDA-approved therapies, is something of a rarity in the highly challenging CGT sector, as a profitable company.
Others, while recognising the value that outcome-based models bring in fostering access, question their sustainability in the long-term. “For newer medicines or in healthcare systems with less experience in CAR-T, outcomes-based agreements remain an effective mechanism for building confidence, establishing a track record, and helping accelerate broader adoption,” says Heath.
He does, however, warn that “over time, as longer-term clinical and real-world evidence accumulates, those agreements can become less necessary because the outcomes and value proposition are already well established. At that stage, they can sometimes create more administrative complexity than practical benefit.”
Manufacturing: The Real Bottleneck
While reimbursement matters, perhaps the key factor in determining whether approved cell and gene therapies ever make it all the way to the patient is manufacturing. It is, in Meek’s words, “foundational.”
It is also fraught with challenges. Unlike traditional biologics, where the process and the finished drug are distinct, in cell and gene therapy the manufacturing process effectively is the product: even small changes in how a therapy is made can alter its potency, quality, and safety. That makes consistency hard to guarantee and oversight far more complex. As Vijay Kumar, acting director of the Office of Therapeutic Products – the division within the US FDA’s CBER charged with regulating CGTs – explains, “There are challenges around manufacturing consistency, comparability, dosing, and immunomodulation, all of which require increasingly sophisticated regulatory oversight.”
To its credit, the FDA is attempting to fill the gaps for manufacturers, many of them smaller companies without prior products or working on technologies with no predecessor to draw from, through designation programmes that let sponsors lean on prior knowledge from established platforms and adopt newer manufacturing approaches such as automation.
Companies themselves – keenly aware of the need to reduce manufacturing costs – have also been working on new models. “In some cases a therapeutic needs to be designed for a single patient with a unique genetic disorder, or for a very small population sharing the same disease category,” notes Madden. “The conventional manufacturing model, producing large-scale batches to support clinical programs and commercialisation, is incredibly inefficient at that scale.”
Madden’s firm Acuitas makes lipid nanoparticles, the fatty bubbles that ferry a genetic payload into the body’s cells, and the same delivery technology behind the COVID-19 mRNA vaccines. Its preformed vesicle (PFV) approach rethinks the order in which a personalised therapy is built. Conventionally the payload is loaded into the LNP during manufacturing, which means producing a complete bespoke batch for every patient.
PFV splits the two steps apart. The LNP, the complex and expensive part, is mass-produced in advance and kept ready in vials on the shelf; the patient-specific payload is synthesised only once that individual is identified, and the two are mixed at the point of administration. Because the hard part is standardised and made at scale rather than rebuilt each time, the per-patient burden shrinks to the payload alone. “The time and cost savings are extraordinary,” exclaims Madden.
Over at Genetix, a lack of manufacturing capacity was a major hurdle to access that is now being addressed. As Meek explains, “We are now doubling our manufacturing capacity by mid-2026, reducing wait times for manufacturing slots and accelerating the patient journey.” He continues, “We have also invested in manufacturing process improvements that increase success rates while optimizing turnaround times. Partnering with industry leading commercial CDMOs has been an important part of that effort. Their expertise in cell and gene therapy manufacturing has helped us scale more effectively, and we intend to continue building on that foundation.”
A Path Already Walked
While access barriers to CGTs in the US persist, the progress already made on reimbursement and manufacturing – as well as lessons from other breakthrough technologies – are fuelling cautious optimism across the sector.
Rawlings uses the analogy of bone marrow transplantation. “20 years ago, transplant was used sparingly, was extremely expensive, and carried significant morbidity,” he concludes. “Over time… transplantation became a standard of care across a growing range of conditions. The cost remains high, but it is an accepted and justified cost. Cell and gene therapy is following an iterative path that I expect will lead to the same outcome.”
