On December 6, 2019 The Janssen Pharmaceutical Companies of Johnson & Johnson reported that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for JNJ-68284528 (JNJ-4528), an investigational B cell maturation antigen (BCMA)-directed chimeric antigen receptor T cell (CAR-T) therapy in previously treated patients with multiple myeloma (Press release, Janssen Pharmaceuticals, DEC 6, 2019, View Source [SID1234552008]). Breakthrough Therapy Designation is granted to expedite the development and regulatory review of an investigational medicine that is intended to treat a serious or life-threatening condition. The criteria for Breakthrough Therapy Designation require preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy.
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"The granting of Breakthrough Therapy Designation for JNJ-4528 is a significant milestone as we continue to accelerate the global development of this innovative CAR-T therapy in collaboration with Legend Biotech," said Sen Zhuang, M.D., Ph.D., Vice President, Oncology Clinical Development, Janssen Research & Development, LLC. "We look forward to continuing to work closely with the U.S. Food and Drug Administration to advance the clinical development program for JNJ-4528 and ultimately bring this BCMA-targeted immunotherapy to patients living with multiple myeloma who are in need of a new therapeutic option."
The Breakthrough Therapy Designation is supported by data from the Phase 1b/2 CARTITUDE-1 study (NCT03548207), an open-label, multicenter clinical trial evaluating the safety and efficacy of JNJ-4528 in adults with relapsed or refractory multiple myeloma who have received at least three prior lines of therapy or are double refractory to a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD); have received a PI, IMiD and an anti-CD38 antibody; and who progressed on or within 12 months of their last line of therapy.1 Currently active in the U.S., the primary objective of the Phase 1b portion of the study is to characterize the safety of JNJ-4528 and confirm the dose for future clinical trials. Phase 2 is evaluating efficacy with a primary endpoint of overall response rate, as defined by the International Myeloma Working Group response criteria, as well as duration of response and overall tolerability. Initial data from the CARTITUDE-1 study will be presented for the first time at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Abstract #577).
The CARTITUDE-1 study design was informed by the Phase 1 LEGEND-2 study (NCT03090659), the first-in-human study with LCAR-B38M CAR-T cells.2 In February 2019, the FDA granted Janssen an Orphan Drug Designation for JNJ-4528. On April 3, 2019, Janssen announced the European Medicines Agency granted a PRIME (PRIority MEdicines) designation for JNJ-4528 based on the CARTITUDE-1 and LEGEND-2 studies.
JNJ-4528, a structurally differentiated CAR-T with two BCMA-targeting single domain antibodies, identifies the investigational product being studied in the U.S. and Europe.3 LCAR-B38M, which has the same CAR construct, identifies the investigational product in China. In December 2017, Janssen entered into a worldwide collaboration and license agreement with Legend Biotech to jointly develop and commercialize LCAR-B38M in multiple myeloma. In China, the Phase 2 CARTIFAN-1 confirmatory trial (NCT03758417), sponsored by Nanjing Legend Biotech Co. Ltd. in collaboration with Janssen, is actively recruiting to further evaluate LCAR-B38M in patients with advanced relapsed or refractory multiple myeloma.4
About CAR-T and BCMA
CAR-T cells are an innovative approach to eradicating cancer cells by harnessing the power of a patient’s own immune system. BCMA is a protein that is highly expressed on myeloma cells.
About CARTITUDE-1
CARTITUDE-1 (NCT03548207) is an ongoing Phase 1b/2, open-label, multicenter study evaluating the safety and efficacy of JNJ-68284528 in adults with relapsed or refractory multiple myeloma who have received at least three prior lines of therapy or are double refractory to a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD); have received a PI, IMiD and an anti-CD38 antibody; and who progressed on or within 12 months of their last line of therapy.1 The primary objective of the Phase 1b portion of the study is to characterize the safety and confirm the dose of JNJ-68284528, which was informed by the first-in-human study with LCAR-B38M CAR-T cells (LEGEND-2). The primary objective for the Phase 2 portion of the study is to evaluate the efficacy of JNJ-68284528 (primary endpoint: overall response rate as defined by the International Myeloma Working Group response criteria).
About Multiple Myeloma
Multiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.5,6 When damaged, these plasma cells rapidly spread and replace normal cells with tumors in the bone marrow.5,6 In 2019, it is estimated that more than 32,000 people will be diagnosed, and nearly 13,000 will die from the disease in the United States.7 While some patients with multiple myeloma have no symptoms, most patients are diagnosed due to symptoms, which can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.8