Legend Biotech (LEGN) The 66th American Society of Hematology (ASH) Annual Meeting and Exposition 2024 summary

Key clinical and commercial updates

• Carvykti has demonstrated significant survival benefit in multiple myeloma, with a hazard ratio of 0.55 versus standard of care and over 4,500 patients treated globally, including both clinical and real-world settings.

• FDA approval in April led to strong uptake in second to fourth line settings, with Q3 2024 global sales reaching $286 million, a 54% sequential increase.

• Nearly half of Carvykti administrations now occur in outpatient settings, improving patient convenience and access.

• No slot limitations currently exist for Carvykti, with bottlenecks mainly related to apheresis capacity at treatment centers.

• The certified network for Carvykti has expanded to 90 centers, supporting broader adoption.

Clinical trial insights and real-world evidence

• CARTITUDE-4 trial showed cilta-cel significantly improved progression-free survival (PFS) and overall survival (OS) in lenalidomide-refractory patients, with a 45% reduction in risk of death compared to standard of care.

• Median PFS was not reached at nearly 34 months, and the 30-month OS rate was 76.4% for cilta-cel versus 63.8% for standard of care.

• MRD negativity rates were substantially higher with cilta-cel, correlating with deeper and more durable responses.

• Real-world data from 16 centers treating over 250 patients showed outcomes and safety similar to clinical trials, with parkinsonism rates around 2%.

• Early use of cilta-cel in first relapse is modeled to provide a three-year survival advantage over reserving it for later lines.

Safety, management, and evolving practices

• Rates of severe CRS and ICANS are lower in CARTITUDE-4 than in earlier trials, attributed to better patient selection and management.

• Delayed neurotoxicity, including parkinsonism, has decreased with proactive monitoring and early intervention, such as low-dose steroids.

• Patient selection, disease burden, and early intervention are key to minimizing adverse events.

• Bridging therapy practices are not standardized and are tailored to patient needs, with a trend toward minimizing its use.

• Outpatient administration is increasingly feasible, with cilta-cel considered best suited for this approach among CAR-T products.