Recently, Legend Biotech announced in Somerset, New Jersey, that the U.S. Food and Drug Administration (FDA) has approved CARVYKTI® (cilta-cel) for the treatment of relapsed or refractory multiple myeloid(RRMM) patients who have received at least one prior line of therapy, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), and are resistant to lenalidomide1. CARVYKTI® is the first and only B-cell maturation antigen (BCMA)-targeted therapy approved for second-line treatment of multiple myeloma patients, including CAR-T therapy, bispecific antibodies and antibody-drug conjugates (ADCs).

The FDA's approval is based on positive results from the CARTITUDE-4 study, which showed that compared with pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, and dexamethasone (PVd), DPd) these two standard treatment regimens, CARVYKTI® can significantly improve the progression-free survival (PFS) of adult patients with relapsed and lenalidomide-resistant multiple myeloma who have received first- to third-line treatment. This result has statistical and clinical significance. The approval follows a unanimous recommendation (11-0) from the Oncology Drugs Advisory Committee (ODAC) in favor of CARVYKTI® for front-line treatment.

The safety profile of CARVYKTI® includes cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), Parkinson and Guillain-Barré syndrome and their related complications, hemophagocytic lymphocytes Boxed warning for HLH/MAS, long-term and recurrent cytopenias, and secondary malignancies including myelodysplastic syndromes, acute myeloid leukemia, and T-cell malignancies . Considerations include increased early mortality, infection, hypogammaglobulinemia, allergic reactions, and effects on the ability to drive and use machines.

The most common non-laboratory adverse reactions (incidence greater than 20%) are fever, cytokine release syndrome, hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue, infection by unknown pathogens, cough, chills, diarrhea, Nausea, encephalopathy, decreased appetite, upper respiratory tract infection, headache, tachycardia, dizziness, dyspnea, edema, viral infection, coagulopathy, constipation and vomiting. The most common Grade 3 or 4 laboratory adverse reactions (incidence greater than or equal to 50%) include lymphopenia, neutropenia, leukopenia, thrombocytopenia, and anemia.

About CARVYKTI® (cilta-cel, Cedarwood)

Cedagene is a chimeric antigen receptor T-cell (CAR-T) therapy that targets B-cell maturation antigen (BCMA), using a transgene of the chimeric antigen receptor (CAR) targeting patient's own T cells. Modifications were made to identify and eliminate BCMA-expressing cells. BCMA is mainly expressed on the surface of malignant multiple myeloma B cell lineage, late B cells and plasma cells. Cedagene's CAR protein has two single-domain antibodies targeting BCMA, which have high affinity for BCMA-expressing cells. After binding to BCMA-expressing cells, the CAR can promote T cell activation and expansion, and then eliminate the target cell.

In December 2017, Janssen entered into an exclusive global license and collaboration agreement with Legend Biotech to develop and commercialize Cedagene. In February 2022, Cedagene was approved by the US FDA for marketing, in May it was granted conditional marketing authorization by the EU EC, and in September it was approved by Japan's MHLW for the treatment of adults with relapsed or refractory multiple myeloma patients with brand name CARVYKTI®. Cedagene received breakthrough therapy designation in the United States in December 2019 and in China in August 2020. In addition, Cedagene was granted priority drug status by the European Commission in April 2019. The US FDA, European EMA and Japanese PMDA granted Orphan Drug designation to Cedagene in February 2019, February 2020 and June 2020 respectively. In March 2022, the Orphan Medicines Committee of the European Medicines Agency unanimously recommended that the orphan drug designation of Cedazolenza should be maintained based on clinical data (complete response rate improved and sustained after treatment).

About CARTITUDE-4

CARTITUDE-4 (NCT04181827) is an international, randomized, open-label, phase 3 study evaluating cedarzumab versus pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab evaluating the efficacy and safety of pomalidomide and dexamethasone (DPd) in adult patients with relapsed and lenalidomide-resistant multiple myeloma who have received first- to third-line therapy, as measured by progression-free survival (PFS) is the primary endpoint of the study.

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