Janssen Receives Positive CHMP Opinion for CARVYKTI®▼ (ciltacabtagene autoleucel; cilta-cel) for Treatment in Earlier Lines of Relapsed and Refractory Multiple Myeloma

Results from the Phase 3 CARTITUDE-4 study, which supported the CHMP recommendation, showed that cilta-cel has the potential to offer significant benefit to patients in earlier lines of treatment1
Most patients with multiple myeloma relapse after current standard treatments and remain in need of additional therapeutic options at earlier stages of the disease1

BEERSE, BELGIUM, 23 February 2024 – The Janssen Pharmaceutical Companies of Johnson & Johnson today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended the approval of a Type II variation for CARVYKTI®▼ (ciltacabtagene autoleucel; cilta-cel) for the earlier treatment of relapsed and refractory multiple myeloma (RRMM). The recommended indication for cilta-cel is for the treatment of adult patients with RRMM, who have received at least one prior therapy, including an immunomodulatory agent (IMiD) and a proteasome inhibitor (PI), have demonstrated disease progression on the last therapy, and are refractory to lenalidomide.2 Cilta-cel is the first chimeric antigen receptor T-cell (CAR-T) therapy to receive a positive CHMP opinion for the treatment of this patient population, as early as after first relapse. Cilta-cel is an innovative CAR-T therapy directed against B-cell maturation antigen (BCMA),3,4 a protein that is highly expressed on myeloma cells.5

“Early resistance to standard treatments is becoming more common in patients with lenalidomide-refractory multiple myeloma, highlighting a need for new options earlier in the course of treatment,” said Edmond Chan, MBChB, M.D. (Res), Senior Director, EMEA Therapeutic Area Lead Haematology, Janssen-Cilag Limited, a Johnson & Johnson Company. “Today’s recommendation from the CHMP recognises the potential of cilta-cel to significantly improve outcomes for eligible patients with relapsed and refractory multiple myeloma, as early as after first relapse.”

The CHMP recommendation for cilta-cel is supported by data from the CARTITUDE-4 study (NCT04181827), the first randomised Phase 3 study evaluating the efficacy and safety profile of cilta-cel versus pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) for the treatment of patients with relapsed and lenalidomide-refractory multiple myeloma who received one to three prior lines of therapy.2,6

“We are committed to the advancement of cilta-cel and other immunotherapies, as we aim to improve outcomes for patients and redefine the multiple myeloma treatment paradigm,” said Sen Zhuang, M.D., Ph.D., Vice President, Clinical Research and Development, Johnson & Johnson Innovative Medicine. “Today’s milestone represents an important step forward in the treatment of this complex disease and in our ultimate goal of one day delivering a cure.”

Cilta-cel is currently approved under conditional marketing authorisation (CMA) for the treatment of adults with RRMM, after three prior lines of therapy.3 In further positive news, the CHMP have now recommended converting the CMA to a standard marketing authorisation, as the obligations of the conditional approval have now been met.2

About Ciltacabtagene Autoleucel (cilta-cel)
Cilta-cel received a CMA from the European Commission in May 2022, for the treatment of adults with RRMM who have received at least three prior therapies, including an IMiD, a PI and an anti-CD38 antibody, and have demonstrated disease progression on the last therapy.33,7 In February 2022, the U.S. Food and Drug Administration (FDA) approved cilta-cel for the treatment of adults with RRMM after four or more prior lines of therapy, including a PI, an IMiD, and an anti-CD38 monoclonal antibody.8,9 For a full list of adverse events and information on dosage and administration, contraindications and other precautions when using cilta-cel please refer to the Summary of Product Characteristics for further information.33 In line with EMA regulations for new medicines and those given conditional approval, cilta-cel is subject to additional monitoring.33

Cilta-cel is a BCMA-directed, genetically modified autologous T-cell immunotherapy, which involves reprogramming a patient’s own T-cells with a transgene encoding a CAR that binds and promotes elimination of cells that express BCMA.10 BCMA is primarily expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B-cells and plasma cells.11,12 The cilta-cel CAR protein features two BCMA-targeting single domain antibodies designed to confer high avidity against human BCMA.10 The CAR-modified T-cells express fusion proteins of antigen receptors against tumour-associated surface antigens and T-cell activation domains, and upon binding to BCMA-expressing cells redirect the effector T-cells and enhance tumour-specific immunosurveillance.13

In December 2017, Janssen Biotech, Inc., a Johnson & Johnson Company, entered into a worldwide licence and collaboration agreement with Legend Biotech USA, Inc. to develop and commercialise cilta-cel.14