EMA - CARVYKTI (ciltacabtagene autoleucel) ottiene la CHMP Opinion positiva

Legend biotech has announced that the European Commission has granted its Decision for Carvykti (ciltacabtagene autoleucel or cilta-cel) for the treatment of patients with relapsed/refractory multiple myeloma (/r MM), who have received at least three prior therapies, including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD) and an anti-CD38 antibody, and have demonstrated disease progression on the last therapy. This EC Marketing Authorization follows the approval of CARVYKTI by the U.S. Food and Drug Administration (FDA) on February 28, 2022.

CARVYKTI 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. 

The approval is based on the pivotal phase 1b/2 CARTITUDE-1 study, which demonstrated an overall response rate (ORR) of 98 percent in patients with relapsed or refractory multiple myeloma following a one-time treatment with ciltacabtagene autoleucel,  including patients who had received a median of six prior treatment regimens (range, 3-18), and had previously received an IMiD, PI and anti-CD38 monoclonal antibody. Findings 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 the patients achieved 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 %) were neutropenia (91 %), cytokine release syndrome (CRS) (88 %), pyrexia (88 %), thrombocytopenia (73 %), anemia (72 %), leukopenia (54 %), lymphopenia (45 %), musculoskeletal pain (43 %), hypotension (41 %), fatigue (40 %), transaminase elevation (37 %), upper respiratory tract infection (32 %), diarrhea (28 %), hypocalcemia (27%), hypophosphatemia (26 %), nausea (26 %), headache (25 %), cough (25 %), tachycardia (23 %), chills (23 %), encephalopathy (22 %), decreased appetite (22 %), oedema (22 %), and hypokalemia (20 %).

As a reminder, Carvykti, a BCMA CAR-T therapy co-developed by Janssen and Legend Biotech, was granted a CHMP positive Opinion back in March 2022. It also had a PRIME designation.

EMA CHMP opinion document is available here

Source: Press-release