U.S. FDA Approves DARZALEX FASPRO® in Combination with Carfilzomib and Dexamethasone for Relapsed or Refractory Multiple Myeloma

Multiple Myeloma (Image source: cancer.gov)

December 02, 2021 /BioValleyBIOON/ -- Johnson & Johnson (JNJ) subsidiary Janssen Pharmaceuticals recently announced that the U.S. Food and Drug Administration (FDA) has approved daratumumab subcutaneous (SC) formulation ——Darzalex Faspro (Chinese trade name: 兆珂速®, generic name: Daratumumab Injection [Subcutaneous Injection]), in combination with Kyprolis (carfilzomib) and dexamethasone (Kd), for the treatment of adult patients with relapsed or refractory multiple myeloma (R/R MM) who have received 1-3 prior lines of therapy.

Darzalex Faspro is a subcutaneous injection (SC) formulation of daratumumab (Darzalex, Janssen Pharmaceuticals). Darzalex is the world's first CD38-mediated, cytolytic antibody drug in the United States.FDAThe first monoclonal antibody drug approved for the treatment of multiple myeloma (MM), its intravenous formulation (IV) was launched in 2015 and has since become a backbone therapy in the clinical treatment of MM, widely used in first-line, second-line, and multi-line treatments.

This approval also marks the 9th indication for Darzalex Faspro.Notably, Darzalex Faspro is currently the first and only subcutaneously administered anti-CD38 monoclonal antibody approved for use in combination with a range of standard treatment regimens for multiple myeloma (MM). Darzalex Faspro is administered as a fixed dose via subcutaneous injection, completing the process in just 3-5 minutes. In contrast, the intravenous (IV) formulation of Darzalex requires infusion through a vein, typically taking several hours. Compared to the IV Darzalex + Kd regimen, the administration time for the subcutaneous (SC) Darzalex Faspro + Kd regimen is significantly reduced, offering further options and treatment convenience for patients with R/R MM, while greatly alleviating the burden of disease management.

In August 2012, Genmab granted Janssen Biotech, Inc., a subsidiary of Johnson & Johnson, the global exclusive license to develop, manufacture, and commercialize daratumumab (Darzalex). The development of Darzalex Faspro utilized Halozyme's ENHANZE® drug delivery technology, with a formulation containing recombinant human hyaluronidase PH20 (rHuPH20).

This approval is supported by the ongoing Phase 2 non-randomized open-label multicenter PLEIADES trial. The trial evaluated the clinical benefits of Darzalex Faspro in combination with four standard-of-care treatment regimens for patients with MM.

The updated data from the study were presented at the 2020 American Society of Hematology (ASH) Annual Meeting, showing that:The response rate of the Darzalex Faspro+Kd regimen is similar to the response rate of the intravenous [IV] Darzalex+Kd regimen in the Phase 3 CANDOR study.The results of the CANDOR study supported the first regulatory approval of the combination of anti-CD38 monoclonal antibody with Kyprolis.

PLEIADES Study Met Primary Endpoint, ShowingThe Overall Response Rate (ORR) for the Darzalex Faspro+Kd regimen was 84.8%., 77.3% of patients achieved a very good partial response (VGPR) or better. In this study, the safety of the Darzalex Faspro + Kd regimen was consistent with the known safety profiles of Darzalex Faspro, Kyprolis, and dexamethasone.

Multiple Myeloma (MM) is an incurable hematologic malignancyTumor, characterized by a recurring cycle of remission and relapse. This is an extremely aggressive disease that affects plasma cells in the bone marrow, where the affected plasma cells replace normal cells. While some MM patients are asymptomatic, most are diagnosed due to related symptoms, including fractures or pain, low red blood cell count, fatigue, high calcium levels, kidney problems, or infections.

Darzalex (Jiaoke, Daratumumab) was first approved for marketing in November 2015. This drug is the world's first approved CD38-mediated cytolytic antibody with broad-spectrum killing activity. It can specifically bind to the highly expressed transmembrane ectoenzyme CD38 molecule on the surface of multiple myeloma and various solid tumor cells. It induces rapid tumor cell death through multiple immune-mediated mechanisms of action, including complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and through...Apoptosis(apoptosis). In addition, Darzalex has also been shown to targetTumorImmune suppressor cells in the microenvironment exhibit immunomodulatory activity.

Kyprolis was first approved for marketing in July 2012. The drug is an irreversible proteasome inhibitor administered intravenously. The proteasome plays a crucial role in cell function and growth by degrading damaged or unneeded proteins. Kyprolis has been shown to block the proteasome, leading to an excessive accumulation of proteins within cells. In certain cells, Kyprolis can cause cell death, particularly in multiple myeloma cells, as these cells are more likely to contain higher levels of abnormal proteins.

Currently,Darzalex and Kyprolis have become important foundational therapies for the treatment of multiple myeloma (MM).The combination of Kypropris (a proteasome inhibitor) and Darzalex (an anti-CD38 monoclonal antibody), two powerful targeted drugs, represents a new approach for treating relapsed or refractory multiple myeloma. (Bioon.com)