The Janssen Pharmaceutical Companies of Johnson & Johnson announced that the European Commission (EC) granted conditional marketing authorization of CARVYKTI® (ciltacabtagene autoleucel; cilta-cel) for the treatment of adults with relapsed and refractory multiple myeloma (RRMM) who have received at least three prior therapies, including an immunomodulatory agent (IMiD), a proteasome inhibitor (PI) and an anti-CD38 antibody, and have demonstrated disease progression on the last therapy. In December 2017, Janssen Biotech, Inc. (Janssen) entered into an exclusive worldwide license and collaboration agreement with Legend Biotech USA, Inc. to develop and commercialize cilta-cel.
“Patients who have relapsed, or for whom treatment regimens have stopped working after experiencing the three major drug classes, typically face poor survival. Despite recent innovation, new therapeutic approaches are still needed,” said Maria-Victoria Mateos, M.D., Ph.D., Consultant Physician in Haematology, University Hospital of Salamanca. “The CARTITUDE-1 data, on which the EC approval is based, show that a single infusion of cilta-cel resulted in durable responses in a heavily pre-treated patient population. These results support the potential of cilta-cel in offering patients and physicians a valuable new treatment option.”
Cilta-cel is a chimeric antigen receptor T-cell (CAR-T) therapy featuring two B-cell maturation antigen (BCMA)-targeting single domain antibodies. CAR-T therapy is specifically developed for each individual patient, and it is administered as a single infusion.
“At Janssen, we are building on nearly 20 years of commitment towards changing what a multiple myeloma diagnosis means for patients and are intent on addressing the high unmet needs that still remain,” said Edmond Chan, MBChB M.D. (Res), EMEA Therapeutic Area Lead Haematology, Janssen-Cilag Limited. "With today’s approval of cilta-cel in Europe, we are pleased to be delivering a new approach to the way in which healthcare professionals can tackle, and hopefully one day overcome, this complex disease.”
Conditional marketing authorization (CMA) is the approval of a medicine that addresses unmet medical needs of patients based on less comprehensive data than normally required, where the benefit of immediate availability of the medicine outweighs the risk, and the applicant is able to provide comprehensive clinical data in the future. This CMA was supported by the pivotal CARTITUDE-1 study, including patients who had received a median of six prior treatment regimens (range, 3–18), and had previously received an IMiD, PI, and an anti-CD38 monoclonal antibody. Findings presented at the American Society of Clinical Oncology (ASCO) 2021 Annual Meeting showed that at a median duration of 18 months follow-up (range, 1.5–30.5), a one-time treatment with cilta-cel resulted in deep and durable responses, with 98 percent (95 percent Confidence Interval [CI], 92.7–99.7) of patients with RRMM responding to therapy (98 percent overall response rate [ORR] (n=97)). Notably, 80 percent of patients achieved a stringent complete response (sCR), a measure in which a physician is unable to observe any signs or symptoms of disease via imaging or other tests after treatment.
The safety of cilta-cel was evaluated in 179 adult patients across two open-label clinical trials (MMY2001 and MMY2003). The most common adverse reactions (≥20 percent) were neutropenia (91 percent), cytokine release syndrome (CRS) (88 percent), pyrexia (88 percent), thrombocytopenia (73 percent), anemia (72 percent), leukopenia (54 percent), lymphopenia (45 percent), musculoskeletal pain (43 percent), hypotension (41 percent), fatigue (40 percent), transaminase elevation (37 percent), upper respiratory tract infection (32 percent), diarrhea (28 percent), hypocalcemia (27 percent), hypophosphatemia (26 percent), nausea (26 percent), headache (25 percent), cough (25 percent), tachycardia (23 percent), chills (23 percent), encephalopathy (22 percent), decreased appetite (22 percent), oedema (22 percent), and hypokalemia (20 percent).
"The approval of Janssen’s first cell therapy is testament to our ongoing commitment to advance science and transform outcomes for those living with multiple myeloma,” said Sen Zhuang, M.D., Ph.D., Vice President, Oncology Clinical Research, Janssen Research & Development, LLC. “We are deeply thankful to the patients, their families, the nurses, and the teams of researchers and study centers who have participated in the clinical study of cilta-cel and made today’s approval possible.”
The longer-term efficacy and safety profile of cilta-cel is being assessed in the ongoing CARTITUDE-1 study. Two-year follow-up results presented most recently at the American Society of Hematology (ASH) 2021 Annual Meeting showed that 98 percent of patients treated with cilta-cel for RRMM responded to therapy (98 percent ORR [n=97]), and the majority of patients achieved sustained depth of response, with 83 percent achieving a sCR at the 22-month follow-up.
As a highly personalized medicine, where a patient’s own T-cells are reprogrammed to target and kill cancer cells, administration of CAR-T therapy requires extensive training, preparation, and certification to ensure the highest quality product and experience for patients. Through a phased approach, Janssen will work diligently to activate a limited network of certified treatment centers and will aim to increase availability of cilta-cel across Europe, in an effort to provide oncologists and patients with treatment in a reliable manner.
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