Sickle cell disease curative therapy uptake exposes the conditioning-regimen access gap

Reading the signal

Two approved curative therapies for sickle cell disease entered the market in 2023 and 2024:

• Lovotibeglogene autotemcel (lenti-globin gene therapy adding a modified beta-globin gene)
• Exagamglogene autotemcel (CRISPR-edited HBB locus to upregulate fetal haemoglobin)

The clinical-evidence picture is strong: substantial reductions in vaso-occlusive crises and transfusion requirements, with most patients achieving complete or near-complete clinical normalisation. Real-world uptake has been more constrained than the clinical evidence would predict.

The constraints:

• Conditioning regimen. Both approved therapies require myeloablative busulfan-based conditioning, with associated short-term toxicity (mucositis, prolonged cytopenias, infection risk) and long-term concerns (fertility, secondary malignancy)
• Specialist-centre infrastructure. The treatment requires apheresis, ex vivo cell modification or editing, conditioning, and autologous infusion across a multi-month protocol. The specialist-centre count globally is small relative to the eligible patient population
• Treatment burden. The full protocol involves multiple specialist-centre visits over 4 to 6 months. Patients with caregiver support and proximity to specialist centres can navigate this; many eligible patients face substantial logistical barriers
• Patient-finding pathway. Sickle cell disease care has historically been fragmented between paediatric haematology, adult haematology, and primary care, and the pathway from these settings to a curative-therapy referral is not standardised

Commercial implications

For sponsors of approved sickle cell curative therapies and adjacent ex vivo gene-therapy programs:

1. Specialist-centre capacity expansion is the commercial growth axis. Sponsors that invest in centre development, specialist training, and patient-coordination infrastructure unlock substantially more commercial volume than the existing centre network supports
2. Non-myeloablative conditioning programs in development would substantially relax the access constraint if pivotal data demonstrates safety and efficacy. Commercial planning is increasingly anticipating this development
3. The patient-finding pathway is part of the commercial responsibility. Reaching the eligible population requires connecting fragmented care settings to the curative-therapy referral pathway

What we are watching

• Non-myeloablative conditioning programs and the rate at which they reach pivotal-stage data
• Specialist-centre expansion globally and the rate at which the access geography improves
• Patient-finding pathway initiatives and what is and is not working in connecting the eligible population to care