Sickle cell disease (SCD) is the world’s most common monogenic disorder, affecting millions globally. Yet despite its prevalence, it has endured decades of underinvestment and limited therapeutic development, resulting in stark and persistent inequities in care.
SCD is a multi-organ condition that can lead to stroke, pulmonary hypertension, kidney failure, vision loss, avascular necrosis, and chronic disability. In high-income countries, comprehensive care programs have dramatically improved survival, with most affected infants now reaching adulthood. But living longer does not necessarily mean living well. Therapeutic options remain limited, and existing treatments are significantly underused, with 70-75 percent of patients not receiving any disease-modifying treatments.
The disparity becomes particularly clear when sickle cell is compared with other genetic conditions of similar prevalence. For example, a recent report in the UK compared SCD care to cystic fibrosis and hemophilia, since these conditions affect similar numbers of people. Despite this, both cystic fibrosis and hemophilia have benefited from more sustained investment in specialized care pathways and a broader range of funded, disease-modifying therapies. By contrast, SCD has a much smaller and more fragmented therapeutic pipeline, with fewer widely accessible disease-modifying options and less uniform delivery of care.
These differences are not simply a reflection of biology. They are the result of long-standing disparities in research investment, drug development, and care infrastructure. Against this backdrop, the recent arrival of gene therapies represents a long-awaited breakthrough. But they also raise a pressing question: whether a healthcare system that has struggled to deliver established treatments at scale is prepared to equitably implement some of the most complex — and costly — therapies ever developed.
A growing therapeutic landscape
SCD is entering a new therapeutic era, but it is not a simple story of progress. Over the past decade, treatment options have expanded from a small set of supportive interventions to a growing continuum that now includes disease-modifying drugs, intensive transfusion strategies such as automated red blood cell exchange, and, most recently, curative gene therapies such as Casgevy and Lyfgenia.
On paper, this represents a transformation in care. In practice, however, access to these options remains uneven, fragmented, and highly dependent on geography, system capacity, and clinical interpretation. Across both established and emerging therapies, the defining constraint is no longer the absence of effective interventions, but the difficulty of consistently delivering them to the estimated 100,000 people living with SCD in the US.
The RBC exchange paradox: known, available, but unevenly used
One of the clearest illustrations of this gap is automated red blood cell exchange (aRBCX), a procedure in which sickled red blood cells are removed from circulation and replaced with healthy donor cells. Despite being a well-established, guideline-supported therapy, its use remains limited in routine practice.
Survey data from US clinicians, shared by Terumo Blood and Cell Technologies at the joint American Society for Apheresis (ASFA) and the World Apheresis Association (WAA) meeting in April, highlighted a striking disconnect between reported access and real-world utilization.
Across multiple physician surveys, 91 percent of respondents reported that their institutions had access to apheresis services, either on-site or via referral pathways. Most also indicated familiarity with transfusion guidelines and a willingness to use aRBCX in appropriate clinical scenarios. Yet, despite this apparent infrastructure, real world data suggests that fewer than three percent of patients with SCD receive aRBCX in any given year.
As one of the study leads, Aaron Haubner, Senior Manager of Regional Medical Affairs and Market Access at Terumo Blood and Cell Technologies, put it, the central question emerging from the data is not whether the therapy exists or is understood — but why it is not reaching patients at scale.
“We see physicians generally report broad access,” he told DDN. “But there’s a disconnect in terms of how many patients actually get it.”
That disconnect, he added, is not driven by a single failure point, but by a layered set of structural and operational constraints that accumulate across the care pathway.
Barriers beyond awareness
When clinicians were asked to identify barriers to prescribing aRBCX, the responses pointed less to clinical uncertainty and more to system-level constraints.
Vascular access challenges, coordination between departments, and limitations in matched blood supply consistently ranked among the most commonly cited obstacles. These were followed closely by logistical issues such as scheduling complexity and the time burden associated with repeated procedures.
“It’s a procedure,” Haubner said. “There’s a lot of coordination that has to take place — scheduling, donor blood availability, and the systems that sit around that.”
It’s not about novelty. Red blood cell exchange is well established. It’s been used for decades. The issue is access to care and the barriers that sit around delivery.
—Aaron Haubner, Terumo Blood and Cell Technologies
Patient-level barriers further compound these challenges. Clinicians cited concerns around insurance coverage, transportation, time away from work or school, and limited patient understanding of the procedure. In aggregate, these factors help explain why even widely available therapies may be inconsistently used outside of specialist centers.
“It’s not about novelty,” he said. “Red blood cell exchange is well established. It’s been used for decades. The issue is access to care and the barriers that sit around delivery.”
What about gene therapy?
In 2023, the FDA approved two gene therapies, Casgevy and Lyfgenia, for SCD treatment. And at least two other gene therapies, reni-cel and risto-cel, are still in clinical development. In a recent study, treatment with Casgevy was associated with sustained reductions in severe vaso-occlusive crises, with follow-up data extending up to 32 months showing patients remained free from severe episodes in reported cohorts.
While highly effective, real-world adoption remains limited. Gene therapy requires intensive conditioning regimens involving chemotherapy, is delivered only at specialized centers, and carries costs estimated in the range of $2–3 million per patient.
If patients are struggling to access established procedures like aRBCX, questions naturally arise about how readily the healthcare system will be able to deliver even more complex, resource-intensive interventions at scale.
Early rollout data show that this isn’t hypothetical. Two years after Casgevy received regulatory approval, only around 60 patients across the US, Europe, and the Middle East had been treated with the gene-editing therapy. This is partially due to difficulties associated with collecting enough stem cells for treatment — a process that relies on apheresis.
SCD alters blood flow characteristics and viscosity, making cell separation during apheresis more complex and less predictable than in other patient populations. Because cell collection is already an inherently variable process, these differences can further reduce yield, and mean patients may require multiple days of apheresis or repeated hospital admissions to reach the target number of cells needed for therapy. In some cases, collections fall short entirely, preventing treatment from proceeding.
Therefore, what should be a routine preparatory step for gene therapy can become one of its most resource-intensive and failure-prone stages.
Personalized approaches for SCD
From a small number of supportive interventions to a continuum of disease modifying drugs, advanced transfusion strategies, and curative gene therapies, the SCD treatment landscape has significantly expanded in the last decade. While this is a huge shift in the right direction, access to these therapies remains highly uneven. The limiting factor is no longer a lack of options, but the ability of healthcare systems to consistently deliver them across different care settings, geographies, and patient populations.
Across clinician surveys, patient data, and early gene therapy rollout data, it’s clear that infrastructure is lagging behind innovation. Therefore, the future of SCD management will depend as much on systems as on science. Expanding therapeutic options alone is not enough. Ensuring equitable benefit will require investment in the underlying infrastructure that makes these therapies usable in practice: coordinated transfusion services, reliable apheresis capacity and optimization, streamlined referral networks, and clearer pathways between specialist and community care.
