On August 5, 2020 Legend Biotech Corporation (NASDAQ:LEGN) reported that the China Center for Drug Evaluation, National Medical Products Administration (CDE, NMPA) has recommended Breakthrough Therapy Designation (BTD) for ciltacabtagene autoleucel (cilta-cel; LCAR-B38M CAR-T cells), an investigational B-cell maturation antigen (BCMA) targeted chimeric antigen receptor (CAR) T-cell therapy being studied for the treatment of adults with relapsed or refractory multiple myeloma (RRMM) (Press release, Legend Biotech, AUG 5, 2020, View Source [SID1234562960]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The BTD for cilta-cel (LCAR-B38M CAR-T cells) is based on the ongoing Phase 2 CARTIFAN-1 study being conducted in China (MMY2002, NCT03758417, CTR20181007), the ongoing Phase 1b/2 CARTITUDE-1 study of cilta-cel (JNJ-4528) being conducted in the US (MMY2001, NCT03548207) and Japan and the Phase 1, first-in-human LEGEND-2 study conducted in China (NCT03090659). Ciltacabtagene autoleucel (cilta-cel) refers to both LCAR-B38M CAR-T cells and JNJ-4528. LCAR-B38M CAR-T cell identifies the investigational product being studied in China and JNJ-4528 identifies the investigational product being studied outside of China, both of which are representative of the same CAR-T cell therapy.

The BTD procedure is part of the recently revised Drug Registration Regulation which went into effect on July 1, 2020. The BTD process is designed to expedite the development and review of therapies that are intended for treatment of serious diseases for which there is no existing treatment and where preliminary evidence indicates advantages of the therapy over available treatment options.1 Cilta-cel is the first product that has been recommended for BTD in China.2 As per the working procedure for BTD (2020 No.82) issued by NMPA on July 8, 2020, CDE had completed the review and recommended to grant the BTD on August 4th, and BTD will be granted after 5 working days of publicity period (August 5 to 12) on the CDE website.

In December 2017, Legend Biotech entered into a worldwide collaboration and license agreement with Janssen Biotech, Inc., one of the Janssen Pharmaceutical Companies of Johnson & Johnson, to jointly develop and commercialize cilta-cel in patients with multiple myeloma. Cilta-cel is a structurally differentiated CAR-T cell therapy containing a 4-1BB co-stimulatory domain and two BCMA-targeting single domain antibodies designed to confer avidity.

"Breakthrough designation recommendation by the China CDE of NMPA represents an important regulatory milestone in the continued development of cilta-cel in multiple myeloma patients in China," said Frank Zhang, PhD, CEO of Legend Biotech. "Legend, in collaboration with Janssen, will continue to advance this investigational therapy in China and globally."

Previously, the following regulatory designations have been granted to Janssen for cilta-cel:

In July 2020, the Korea Ministry of Food and Drug Safety granted orphan drug designation.3
In June 2020, the Japan Ministry of Health, Labor and Welfare granted orphan drug designation.4
In February 2020, the European Commission granted orphan designation.5
In December 2019, the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation.6
In April 2019, the European Medicines Agency granted Janssen a PRIME (PRIority MEdicines) designation.7
In February 2019, the FDA granted Janssen orphan drug designation for the treatment of multiple myeloma.8
About the Clinical Development Program

CARTIFAN-1
The Phase 2 CARTIFAN-1 confirmatory trial (MMY2002, NCT03758417, CTR20181007) is being conducted in China to further evaluate cilta-cel (LCAR-B38M CAR-T cells) in patients with RRMM who have received at least 3 prior lines of therapy and have received a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD); and documented disease progression within 12 months of starting the most recent therapy. 9

CARTITUDE-1
Cilta-cel (JNJ-4528) is currently being investigated in the Phase 1b/2 CARTITUDE-1 (MMY2001, NCT03548207) pivotal study conducted in US and Japan for the treatment of patients with multiple myeloma who have received at least 3 prior lines of therapy or are double refractory to a PI and IMiD; received a PI, an IMiD and anti-CD38 antibody; and documented disease progression within 12 months of starting the most recent therapy. 10

CARTITUDE-2
The global, multi-cohort Phase 2 CARTITUDE-2 (MMY2003, NCT04133636) study, cilta-cel (JNJ-4528) is actively recruiting patients with multiple myeloma in various clinical settings. This study is being conducted to evaluate the overall minimal residual disease (MRD) negative rate of participants who receive JNJ-4528 to further explore efficacy and safety in earlier patient populations.11

CARTITUDE-4
The global, Phase 3 CARTITUDE-4 (MMY3002, NCT04181827) study, cilta-cel (JNJ-4528) is actively recruiting patients with multiple myeloma who have received 1-3 prior lines of therapy including a PI and IMiD and are refractory to lenalidomide. The study is being conducted to evaluate the efficacy of JNJ-4528 compared to standard therapies7 including daratumumab, pomalidomide and low-dose dexamethasone (DPd) or pomalidomide, bortezomib and low-dose dexamethasone (PVd).12

LEGEND-2
LEGEND-2 (NCT03090659) is an ongoing, Phase 1, single-arm, open-label, first-in-human, study of 74 patients being conducted at four participating hospitals in China evaluating the efficacy and safety of LCAR-B38M CAR-T cells for the treatment of patients with relapsed or refractory multiple myeloma.13

About Multiple Myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excessive proliferation of plasma cells.14

Although treatment may result in remission, unfortunately, patients will most likely relapse as there is currently no cure.15 Refractory multiple myeloma is when a patient’s disease is non-responsive or progresses within 60 days of their last therapy.16,17 Relapsed myeloma is when the disease has returned after a period of initial, partial or complete remission and does not meet the definition of being refractory.18 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections.19 Patients who relapse after treatment with standard therapies, including protease inhibitors and immunomodulatory agents, have poor prognoses and few treatment options available.20