Legend Biotech Unveils Groundbreaking 5-Year Survival Data for CARVYKTI in Multiple Myeloma at 2025 ASCO Annual Meeting

Published: 2025-06-04 06:40:16 ET LEGN

Published on 06/04/2025 at 06:40

SOMERSET - Legend Biotech Corporation (NASDAQ: LEGN) (Legend Biotech), a global leader in cell therapy, announced new long-term results from the CARTITUDE-1 study in heavily pretreated relapsed/refractory multiple myeloma (RRMM) patients.

RRMM patients were treated with a single infusion of CARVYKTI (ciltacabtagene autoleucel; cilta-cel) with no maintenance or subsequent myeloma therapy. Notably, an unprecedented 33% (32 of 97) of patients remained progression-free for five years or more.

These data were featured in an oral presentation at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #7505). To date, more than 6,500 patients have been treated with CARVYKTI, the first and only CAR T-cell treatment in multiple myeloma to show overall survival benefit vs. standard of care.

In a subset of 12 patients from a single center from this analysis who underwent serial minimal residual disease (MRD) assessments, all 12 patients remained progression-free =5 years, were MRD-negative and showed no disease on annual PET/CT scans for five years.

'The durability and consistency we're seeing with CARVYKTI in the CARTITUDE-1 study is truly remarkable,' said Sundar Jagannath, M.D., Network Director, Multiple Myeloma Center of Excellence for Multiple Myeloma at The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York. 'These data offer real hope for long-term disease control in a population that previously had limited options.' (++)

At median follow-up of 61.3 months in CARTITUDE-1 (n=97), patients treated with CARVYKTI demonstrated a median OS of 60.7 months (95% CI, 41.9-NE). Thirty-two patients (33%) remained progression-free for =5 years after a single CARVYKTI infusion, with no further multiple myeloma treatment. These patients had a median age of 60 years (range, 43-78), received a median of 6.5 prior lines of therapy (range, 3-14), and included patients with high-risk cytogenetics (23.3%), with extramedullary disease (EMD) (12.5%), triple-class refractory disease (90.6%), and penta-drug refractory disease (46.9%). Prior to enrollment, their median time to progression following the last line of therapy was four months.

Safety signals were consistent with the known benefit/risk safety profile of CARVYKTI. No new movement or neurocognitive treatment-emergent adverse events (MNTs)/parkinsonism were reported. Two new cases of second primary malignancies were reported, both solid tumors.

These data were also simultaneously published in the Journal of Clinical Oncology.

'This five-year survival data highlights the potential of CARVYKTI to fundamentally change treatment expectations for patients with relapsed or refractory multiple myeloma,' said Mythili Koneru, M.D., Ph.D., Chief Medical Officer of Legend Biotech. 'For one-third of these heavily pre-treated patients to remain progression-free for five years after a single infusion-and without needing further myeloma therapy-represents a potential paradigm shift in how we treat relapsed or refractory multiple myeloma.'

In addition to the long-term survival data, the following updates were provided during poster presentations

CARTITUDE-4: Data from intent-to-treat high-risk subgroups show CARVYKTI improved progression-free survival (PFS) and overall survival (OS) versus standard therapy (Abstract #7539)

CARTITUDE-4 is a Phase 3 study evaluating CARVYKTI versus two standard of care (SOC) therapies of pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, dexamethasone (DPd) in patients with relapsed, lenalidomide-refractory multiple myeloma after one to three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD).

At median follow-up of 33.6 months, CARVYKTI demonstrated consistent and durable benefit in PFS and OS compared with SOC across high-risk subgroups, including cytogenetic risk groups, EMD status, and number of prior lines of therapy.

ABOUT CARVYKTI (CILTACABTAGENE AUTOLEUCEL; CILTA-CEL)

Ciltacabtagene autoleucel is a BCMA-directed, genetically modified autologous T-cell immunotherapy, which involves reprogramming a patient's own T-cells with a transgene encoding a chimeric antigen receptor (CAR) that identifies and eliminates cells that express BCMA. The cilta-cel CAR protein features two BCMA-targeting single domain antibodies designed to confer high avidity against human BCMA. Upon binding to BCMA-expressing cells, the CAR promotes T-cell activation, expansion, and elimination of target cells.

In December 2017, Legend Biotech entered into an exclusive worldwide license and collaboration agreement with Janssen Biotech, Inc. (Janssen), a Johnson & Johnson company, to develop and commercialize cilta-cel. In February 2022, cilta-cel was approved by the U.S. Food and Drug Administration (FDA) under the brand name CARVYKTI for the treatment of adults with relapsed or refractory multiple myeloma. In April 2024, cilta-cel was approved for the second-line treatment of patients with relapsed/refractory myeloma who have received at least one prior line of therapy including a proteasome inhibitor, an immunomodulatory agent, and are refractory to lenalidomide.

In May 2022, the European Commission (EC) granted conditional marketing authorization of CARVYKTI for the treatment of adults with relapsed and refractory multiple myeloma. In September 2022, Japan's Ministry of Health, Labour and Welfare (MHLW) approved CARVYKTI. Cilta-cel was granted Breakthrough Therapy Designation in the U.S. in December 2019 and in China in August 2020. In addition, cilta-cel received a PRIority MEdicines (PRIME) designation from the European Commission in April 2019. Cilta-cel also received Orphan Drug Designation from the U.S. FDA in February 2019, from the European Commission in February 2020, and from the Pharmaceuticals and Medicinal Devices Agency (PMDA) in Japan in June 2020. In March 2022, the European Medicines Agency's Committee for Orphan Medicinal Products recommended by consensus that the orphan designation for cilta-cel be maintained on the basis of clinical data demonstrating improved and sustained complete response rates following treatment.

ABOUT CARTITUDE-1

CARTITUDE-1 (NCT03548207) is a Phase 1b/2, open-label, multicenter study evaluating the safety and efficacy of cilta-cel in adults with relapsed and/or refractory with multiple myeloma who have received at least 3 prior lines of therapy or are double refractory to a PI and IMiD, received a PI, an IMiD, and anti-CD38 antibody and documented disease progression within 12 months of starting the most recent therapy. The primary objective of the Phase 1b portion of the study was to characterize the safety and confirm the recommended Phase 2 dose of cilta-cel, informed by the first-in-human study with LCAR-B38M CAR-T cells (LEGEND-2). The Phase 2 portion further evaluated the efficacy of cilta-cel with overall response rate as the primary endpoint.

ABOUT CARTITUDE-4

CARTITUDE-4 (NCT04181827) is an ongoing, international, randomized, open-label Phase 3 study evaluating the efficacy and safety of cilta-cel versus pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) in adult patients with relapsed and lenalidomide-refractory multiple myeloma who received one to three prior lines of therapy, including a PI and an IMiD.

ABOUT LB1908

NCT05539430 is a Phase 1, open label, dose escalation, multicenter study to evaluate Claudin 18.2-targeting CAR-T cells (LB1908) in adult patients with unresectable, locally advanced or metastatic gastric, gastroesophageal junction, esophageal, or pancreatic adenocarcinoma.

ABOUT LB2102

NCT05680922 is a Phase 1, first-in-human, open-label, multicenter, dose escalation and expansion study of DLL3-targeted chimeric antigen receptor T-cells (LB2102) in patients with extensive stage small cell lung cancer or large cell neuroendocrine lung cancer.

ABOUT MULTIPLE MYELOMA

Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excessive proliferation of plasma cells.6 In 2024, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma, and more than 12,000 people will die from the disease in the U.S.7 While some patients with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections.

ABOUT GASTRIC, ESOPHAGEAL AND PANCREATIC CANCERS

Stomach, esophageal and pancreatic cancers affect the tissue or glands lining these organs. They are often diagnosed when the diseases have progressed to advanced stages. In the U.S., there are an estimated 123,920 people living with stomach cancer and 49,084 living with esophageal cancers.9,10 An estimated 89,248 people in the U.S. live with pancreatic cancer. While all three cancers are treatable, the five-year survival rate is just 32% for gastric cancer; 20% for esophageal cancer and 11.5% for pancreatic cancer, with definitive treatment at all stages of progression.

ABOUT SMALL CELL LUNG CANCER

Lung cancer is a leading cause of cancer deaths, contributing to 25 percent of all cancer-related fatalities annually in the United States. Small cell lung cancer (SCLC) is the most aggressive, and accounts for roughly 10-15 percent of lung cancer cases in the United States. An estimated 30,000 to 35,000 people are newly diagnosed with the disease each year.16 This cancer becomes more difficult to treat once it has spread and becomes extensive stage SCLC. Approximately 60 to 70 percent of SCLC patients are diagnosed with metastatic SCLC.

ABOUT LEGEND BIOTECH

With over 2,600 employees, Legend Biotech is the largest standalone cell therapy company and a pioneer in treatments that change cancer care forever. The company is at the forefront of the CAR-T cell therapy revolution with CARVYKTI, a one-time treatment for relapsed or refractory multiple myeloma, which it develops and markets with collaborator Johnson & Johnson. Centered in the US, Legend is building an end-to-end cell therapy company by expanding its leadership to maximize CARVYKTI's patient access and therapeutic potential. From this platform, the company plans to drive future innovation across its pipeline of cutting-edge cell therapy modalities.

CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS

Statements in this press release about future expectations, plans, and prospects, as well as any other statements regarding matters that are not historical facts, constitute 'forward-looking statements' within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements relating to Legend Biotech's strategies and objectives; statements relating to CARVYKTI, including Legend Biotech's expectations for CARVYKTI and its therapeutic potential; statements related to the potential results from ongoing studies in the CARTITUDE clinical development program and the potential benefits of Legend Biotech's product candidates. The words 'anticipate,' 'believe,' 'continue,' 'could,' 'estimate,' 'expect,' 'intend,' 'may,' 'plan,' 'potential,' 'predict,' 'project,' 'should,' 'target,' 'will,' 'would' and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors. Legend Biotech's expectations could be affected by, among other things, uncertainties involved in the development of new pharmaceutical products; unexpected clinical trial results, including as a result of additional analysis of existing clinical data or unexpected new clinical data; unexpected regulatory actions or delays, including requests for additional safety and/or efficacy data or analysis of data, or government regulation generally; unexpected delays as a result of actions undertaken, or failures to act, by our third party partners; uncertainties arising from challenges to Legend Biotech's patent or other proprietary intellectual property protection, including the uncertainties involved in the U.S. litigation process; government, industry, and general product pricing and other political pressures; as well as the other factors discussed in the 'Risk Factors' section of Legend Biotech's Annual Report on Form 20-F filed with the Securities and Exchange Commission on March 11, 2025. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described in this press release as anticipated, believed, estimated or expected. Any forward-looking statements contained in this press release speak only as of the date of this press release. Legend Biotech specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise.

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