Accelerating access to gene therapy: Lessons from commercial implementation in sickle cell disease and transfusion-dependent thalassemia

Background

Commercial gene therapy for hemoglobinopathies requires coordinated execution across payers, sites, and manufacturing. With >900 patient-years of follow-up, beti-cel (Zynteglo; US approval Aug-2022) and lovo-cel (Lyfgenia; US approval Dec-2023) are now in routine use. We characterized a national ecosystem spanning Qualified Treatment Centers (QTCs), specialty labs, centralized manufacturing, and program operations to quantify real-world implementation timelines, uptake, and drivers in routine practice.

Methods

Operational data through Nov 14, 2025 were collated from US QTCs with patients prescribed Zynteglo or Lyfgenia. Updated data will be presented. Milestones were enrollment, scheduling, collection, manufacturing, and infusion. Time-to-event analyses and mixed-effects models quantified effects of program maturity, collection burden, and site-level factors.

Results

392 patients were enrolled across programs, with 94.1% treated or in progress. Across the network of 70 active QTCs, 37 received Lyfgenia, 78 received Zynteglo and an additional 219 patients had initiated collection. Early Zynteglo operational experience enabled rapid Lyfgenia launch. The time from approval to first enrollment was nearly 2-fold faster, and first-quarter enrollment rates were 167% higher, driven by 6-fold more QTC activations. Annual Lyfgenia enrollment doubled between 2024 and 2025, demonstrating sustained acceleration in the SCD program (Figure 1). Median time from enrollment to infusion was 8.0 months for Lyfgenia and 9.9 months for Zynteglo; 76% and 72% of patients, respectively, were treated within 12 months. These timelines demonstrate that commercial SCD gene therapy can be delivered within one year of enrollment in routine practice across a distributed national network. Among Lyfgenia patients infused or in progress with ≥6 months of follow-up from first collection, 82% (35/43) required one or two collections, consistent with clinical trial experience; each additional collection cycle added a mean 82 days to time to infusion (p < 0.001). Time from enrollment to infusion correlated with the interval from scheduling to collection, suggesting that early procedural delays shape overall treatment timelines. Time from scheduling to collection modestly increased over time, highlighting scalability needs as demand grows. Key operational opportunities include streamlining coverage approvals, reducing the need for multiple collection cycles, supporting site readiness, and increasing manufacturing capacity. Eighty-four percent of US Medicaid beneficiaries with SCD and 88% of active QTCs are located in states participating in the CMS Innovation Center’s Cell and Gene Therapy (CGT) Access Model. Although most patients treated to date had initiated therapy prior to model implementation, this outcomes-based framework may further streamline Medicaid access. Given that a substantial proportion of individuals with SCD are covered by Medicaid, this alignment is particularly relevant for equitable access.

Conclusions

Commercial gene therapy for SCD can be delivered at a national scale within existing treatment center networks, with the majority of patients infused within 12 months of enrollment. Cross-program learning and centralized support enabled faster treatment across a national network. Alignment between expanding QTC networks, payer coverage, and emerging policy frameworks will continue to improve timely access. Initiatives to reduce the number of collection cycles, expand site and manufacturing capacity and optimize the patient journey will be critical to extend treatment to the many remaining eligible patients. While more than 300 patients have initiated treatment, tens of thousands remain eligible, highlighting the ongoing need for system readiness and expansion to fully realize the promise of advanced therapies.

Cumulative number of patients on treatment journey for Zynteglo and Lyfgenia