Carvykti EU Approval on May 26, 2022

Carvykti EU Approval on May 26, 2022

CARVYKTI® (Cilta-cel, Ciltacabtagene Autoleucel) Approved for Marketing in the European Union

CARVYKTI® (Cilta-cel, Ciltacabtagene Autoleucel) is the first product of Legend Biotech to be approved by the European Commission (EC).

This approval is primarily based on the key results from the pivotal Phase 1b/2 CARTITUDE-1 study. The results showed that Cilta-cel demonstrated a high overall response rate (ORR) of up to 98% in a single treatment for patients with relapsed or refractory multiple myeloma.

On May 26, 2022, local time, Legend Biotech (NASDAQ: LEGN) officially announced in Somerset, New Jersey, USA, that the European Commission (EC) has granted conditional marketing authorization for CARVYKTI® (Ciltacabtagene Autoleucel, Cilta-cel) for the treatment of adult patients with relapsed or refractory multiple myeloma (R/R MM) who have previously received at least three therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody, and have demonstrated disease progression on the last therapy. Legend Biotech and Janssen entered into an exclusive worldwide license and collaboration agreement in December 2017 to develop and commercialize Cilta-cel.

CARVYKTI® is a chimeric antigen receptor (CAR) T-cell immunotherapy with two BCMA (B-cell maturation antigen)-targeting single-domain antibodies. CAR-T therapy is a personalized treatment administered as a one-time intravenous infusion.

“The approval of CARVYKTI® by the European Commission marks an important milestone for Legend Biotech as our first approved product in the region, further advancing our commitment to bringing innovative cell therapies to patients with high unmet medical needs. The CARTITUDE-1 study data demonstrate the potential for CARVYKTI® to provide an effective treatment option for multiple myeloma patients who have received extensive pretreatment and require prolonged treatment-free intervals. We look forward to working with our partner Janssen to bring this novel therapy to patients across Europe.”

Dr. Ying Huang, CEO of Legend Biotech

This approval is based on the key results from the CARTITUDE-1 study, which included patients who had previously received a median of six prior lines of therapy (range 3-18), including proteasome inhibitors (PIs), immunomodulatory agents (IMiDs), and anti-CD38 antibodies. The results showed that in a median follow-up of 18 months (range 1.5-30.5), 97 R/R MM patients who received a single dose of Ciltacabtagene Autoleucel experienced early, deep, and durable responses, with an overall response rate (ORR) of 98% (95% CI: 92.7-99.7). Notably, 80% of patients achieved stringent complete response (sCR), meaning no detectable disease by imaging or other assessments after treatment.

The safety of Ciltacabtagene Autoleucel was evaluated in two open-label clinical studies (MMY2001 and MMY2003) with 179 enrolled adult patients. The most common adverse reactions (≥20%) were neutropenia (91%), cytokine release syndrome (CRS) (88%), fever (88%), thrombocytopenia (73%), anemia (72%), leukopenia (54%), lymphopenia (45%), musculoskeletal pain (43%), hypotension (41%), fatigue (40%), increased transaminases (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%), edema (22%), and hypokalemia (20%).

“For patients with relapsed or refractory multiple myeloma who have exhausted available treatment options, there remains an unmet medical need. The CARTITUDE-1 trial data demonstrate that Cilta-cel provides deep and durable responses for patients who have received extensive pretreatment. Today’s approval by the European Commission reinforces the potential for Cilta-cel to offer a new treatment option for multiple myeloma patients in Europe.”

Hermann Einsele

Julius-Maximilians-University Würzburg

Full Professor of Internal Medicine and Director of the Second Medical Center

As a highly personalized medicine, CAR-T therapy requires extensive training, preparation, and certification to ensure the delivery of high-quality products and experiences for patients by re-engineering their own T cells to target and kill cancer cells. Through a phased approach, Legend Biotech’s strategic partner Janssen will initiate a network of certified treatment centers across Europe, aiming to improve access to Cilta-cel and provide a reliable treatment option for oncologists and patients.

This marketing authorization from the European Commission (EC) follows the U.S. Food and Drug Administration (FDA) approval of CARVYKTI® on February 28, 2022.

About CARVYKTI® (Ciltacabtagene Autoleucel, Cilta-cel)

Cilta-cel is a BCMA (B-cell maturation antigen)-directed chimeric antigen receptor T-cell (CAR-T) therapy that uses a CAR to modify a patient’s own T cells to identify and eliminate cells expressing BCMA. BCMA is primarily expressed on malignant multiple myeloma B cells, mature B cells, and plasma cells. The CAR protein in CARVYKTI® contains two BCMA-targeting single-domain antibodies with high affinity for BCMA-expressing cells, and upon binding to BCMA, the CAR promotes T-cell activation, expansion, and elimination of target cells.

In December 2017, Janssen and Legend Biotech entered into an exclusive worldwide license and collaboration agreement to develop and commercialize CARVYKTI®.

In April 2021, Legend Biotech announced the submission of a marketing authorization application to the European Medicines Agency (EMA) seeking approval for Cilta-cel for the treatment of patients with relapsed or refractory multiple myeloma. In addition to receiving Breakthrough Therapy Designation from the U.S. in December 2019, Cilta-cel was included in the “Breakthrough Therapy” category in China in August 2020. Cilta-cel received Orphan Drug Designation from the U.S. FDA, EMA, and Japan’s PMDA in February 2019, February 2020, and June 2020, respectively. Cilta-cel was approved by the U.S. FDA in February 2022.

About CARTITUDE-1

CARTITUDE-1 (NCT03548207) is an ongoing Phase 1b/2, open-label, single-arm, multicenter study evaluating the safety and efficacy of Ciltacabtagene Autoleucel for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD), and an anti-CD38 monoclonal antibody. Of the 97 patients enrolled in the study, 99% were triple-class refractory (their disease was refractory to an IMiD, a PI, and an anti-CD38 monoclonal antibody), and 88% were triple-class exposed.