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

Introduction: The commercial delivery of gene therapy for hemoglobinopathies requires not only scientific rigor but also system-level coordination across payers, sites, and providers. With >700 patient-years of follow-up in clinical trials, Zynteglo (approved Aug 2022 for thalassemia) and Lyfgenia (approved Dec 2023 for sickle cell disease) are now in real-world use in the United States. This analysis examines the coordinated implementation of a national treatment ecosystem – spanning Qualified Treatment Centers (QTCs), specialty testing laboratories, centralized manufacturing facilities, and program operations – designed to enable scalable and equitable access.

Methods: We analyzed operational data from patients prescribed Zynteglo and Lyfgenia through July 1, 2025 across 47 US-based QTCs with enrolled patients. Patients were tracked through onboarding stages: enrollment, scheduling, cell collection, manufacturing, and infusion. Time-to-event analyses and mixed effects multivariable models were used to isolate the contribution of gene therapy program maturity, collection burden, and site-level factors to treatment timelines.

Results:Since commercial launch, 312 patients enrolled across both programs, with 95.5% treated, in manufacturing or progressing toward collection. 77 patients (25%) have been infused across 25 QTCs and 131 (42%) are scheduled or have completed at least one stem cell collection. The remaining enrolled patients were not yet scheduled for collection.

Zynteglo approval preceded Lyfgenia by 16 months (M) and was associated with longer post-infusion follow-up: 6.9M (range: 0.2-26.2) versus 3.5M (0.2-9.6) for Lyfgenia. However, early experience with Zynteglo facilitated a more rapid Lyfgenia uptake: time from approval to first patient enrollment was nearly 2-fold faster and first quarter enrollment rates were 167% higher – driven by 6-fold more first quarter QTC activations. Annual Lyfgenia enrollment also doubled between 2024 and 2025, underscoring continued acceleration in the program.

Using a linear regression model adjusting for time since product approval, the mean time from enrollment to start of collection was 5.1 months (95% CI: 4.4–5.8). Time from enrollment to infusion correlated with the interval from scheduling to collection (r = 0.55, p < 0.001), suggesting that early procedural delays may contribute to overall treatment timelines. These delays may reflect not only logistical barriers but also the need for comprehensive patient and provider education, highlighting an opportunity to accelerate informed decision-making as familiarity with gene therapy grows.

Time to infusion varied widely (median: 8.5M; range: 3.9–17.9), as shown in a multivariable linear model driven largely (40%) by the collection-to-manufacture interval, reflecting the operational burden of repeated mobilization and collection. In a mixed effects model, longer time to infusion was primarily driven by the number of apheresis collections required (+70 days per collection, p < 0.001). Among Zynteglo-treated patients who completed infusion, 82% (49/60) achieved infusion after single collection. In the Lyfgenia cohort, where most patients remain in progress, 19% (4/21) of those who started collection at least 6 months prior to the data cut have required more than two collections, consistent with clinical trial experience.

Operational bottlenecks, such as coverage approvals, multiple collections, site readiness delays, and manufacturing capacity emerged as opportunities for targeted process improvement. Time to scheduled collection modestly increased over time, emphasizing the need for scalable workflows and coordinated planning. Notably, more active sites had faster treatment timelines (p = 0.02), suggesting that higher throughput may reflect institutional experience and operational efficiency.

Conclusions: This real-world analysis is the first to characterize commercial gene therapy implementation, demonstrating scalable delivery and accelerated access over time. Cross-program learning and centralized support enabled faster treatment across a national network. With published payer coverage for >250M lives – without a single ultimate denial – these findings offer a functioning model for gene therapy implementation. 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.