The Potential of CAR T Therapies: Q&A with Ying Huang

Ying Huang, PhD
CEO
Legend Biotech

Legend Biotech revealed data collected from the CARTITUDE-2 Cohort D study at ASCO 2024 in Chicago in late May and early June of this year. The study is testing the ability of Carvykti to treat patients with relapsed/refractory multiple myeloma. The company’s CEO, Ying Huang, PhD, spoke with Pharmaceutical Executive about these results and their implications.

Pharmaceutical Executive: Can you explain the importance of the results of the Phase 2 CARTITUDE-2 Cohort D study?
Ying Huang: This data is from the earliest patient population to receive CARVYKTI (ciltacabtagene autoleucel; cilta-cel) to date that we have reported results for. We recently presented initial data for the first time from our global, multi-cohort Phase 2 CARTITUDE-2 Cohort D study evaluating CARVYKTI in multiple myeloma patients with less than a complete response (CR) after front-line autologous stem cell transplant (ASCT) during an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #7505)¹ and as an encore oral presentation at the 2024 European Hematology Association (EHA) Congress (Abstract #S205)². Results showed these patients experienced deep and durable responses following a single infusion of CARVYKTI with or without lenalidomide maintenance. Given the historically poor clinical outcomes in patients with a suboptimal response after ASCT front-line therapy, the efficacy, and safety data from Cohort D is promising and suggests CARVYKTI could benefit patients earlier in the treatment regimen.

PE: What potential do CAR T therapies have in earlier lines of MM treatment?
Huang: We are studying CARVYKTI as a first-line treatment in our CARTITUDE-5 and CARTITUDE-6 studies to determine whether patient outcomes could be improved even further compared to standard therapies.This is a very exciting time in the field of multiple myeloma research, and we are proud to be offering hope to patients and their families.According to the Leukemia & Lymphoma Society,³ between 2000 and 2018, the 5-year relative survival rate for multiple myeloma patients increased by 20%. With recent developments and approvals in the CAR-T space, median survival will probably be even longer. CAR-T therapies offer a promising treatment option for patients who do not respond effectively to traditional lines of therapies. As of April 5, 2024, the U.S. Food and Drug Administration (FDA) approved⁴ CARVYKTI for the second-line treatment of multiple myeloma. CARVYKTI demonstrated powerful efficacy and manageable safety as a personalized, one-time infusion in the earlier treatment of patients with relapsed/refractory multiple myeloma. We believe treating patients with CARVYKTI earlier in the treatment paradigm when they are healthier, and their immune systems are stronger may result in better outcomes for patients.

PE: What do these advancements mean for patients and prescribers
Huang: The treatment burden can weigh heavily on patients with multiple myeloma, imposing significant physical, emotional, and practical challenges impacting their daily routine and quality of life. Patients who have been on drug therapy for an extended period quickly become weary from taking a pill daily or receiving injections every 1-2 weeks. A one-time treatment affords patients the benefit of a treatment-free period and allows them to resume their daily activities, with many patients even returning to work. The expanded label of CARVYKTI transforms the treatment paradigm for multiple myeloma by providing patients and physicians with personalized immunotherapy that can be used earlier in the treatment regimen. This new indication for this one-time infusion has the potential to give the patients a treatment-free respite as early as first relapse.

PE: What are the next steps for CARVYKTI?
Huang: In addition to investigating CARVYKTI’s potential as a first-line therapy, we are exploring ways to make CARVYKTI more accessible beyond the tertiary care centers, where it is most often administered currently. Right now, we are in roughly 75 certified centers and plan to roll out CARVYKTI to about 90-100 hospitals by the end of 2024. We are launching the first phase of our pilot program with the University of Pennsylvania that enables physicians at the health system’s regional hospitals in the Philadelphia area to administer CARVYKTI. We will work with UPenn’s experts to train physicians in those satellite hospitals to use CARVYKTI. The second phase of our approach will involve working with larger community oncology practices. We, along with our development partner J&J, are committed to making CARVYKTI available to all patients who could benefit from it no matter where they live.

Sources

1. Efficacy and Safety of Ciltacabtagene Autoleucel ± Lenalidomide Maintenance in Newly Diagnosed Multiple Myeloma with Suboptimal Response to Frontline Autologous Stem Cell Transplant: CARTITUDE-2 cohort D. ASCO. https://meetings.asco.org/abstracts-presentations/231722
2. Abstract S205. EHA. https://library.ehaweb.org/eha/2024/eha2024-congress/422309/wilfried.roeloffzen.ciltacabtagene.autoleucel.lenalidomide.maintenance.in.html?f=listing%3D0%2Abrowseby%3D8%2Asortby%3D1%2Asearch%3Dciltacabtagene
3. Updated Data on Blood Cancers. Leukemia and Lymphoma Society. https://www.lls.org/sites/default/files/2023-08/PS80_Facts_2022_2023.pdf
4. Legend Biotech’s CARVYKTI® (ciltacabtagene autoleucel) Becomes the First and Only BCMA-Targeted CAR-T Cell Therapy Approved by the FDA for Second-Line Treatment of Multiple Myeloma. Legend Biotech. April 5, 2024. https://legendbiotech.com/legend-news/legend-biotechs-carvykti-ciltacabtagene-autoleucel-becomes-the-first-and-only-bcma-targeted-car-t-cell-therapy-approved-by-the-fda-for-second-line-treatment-of-multiple-myeloma-2/