Darzalex Faspro Becomes First FDA-Approved Treatment for Newly Diagnosed Light Chain (AL) Amyloidosis

January 15, 2021 News /BioValleyBIOON/ -- Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson (JNJ), recently announced that the U.S. Food and Drug Administration (FDA) has approved the subcutaneous (SC) formulation of Darzalex (daratumumab)—Darzalex Faspro (daratumumab and hyaluronidase-fihj)—in combination with bortezomib, cyclophosphamide, and dexamethasone (D-VCd regimen), for the treatment of newlyDiagnosisadult patients with light-chain (AL) amyloidosis. Currently, the application for Darzalex SC formulation for this indication is also under review by the European Union.

It is worth mentioning that,Darzalex Faspro is the first and only medication for the treatment of AL amyloidosis.Clinical data show that, compared with patients receiving the standard VCd regimen (bortezomib + cyclophosphamide + dexamethasone), those receiving the D-VCd regimenThe rate of complete hematologic response increased threefold (hemCR: 42% vs. 13%, p < 0.0001), with sustained reduction in disease markers, indicating a deep hematologic response.

Darzalex Faspro is a subcutaneous (SC) formulation of daratumumab (Darzalex, Zhaoke®). Darzalex is the world’s first CD38-mediated, cytolytic antibody drug, approved in the United States.FDAThe first monoclonal antibody drug approved for the treatment of multiple myeloma (MM), with its intravenous (IV) formulation launched in 2015, has now become a cornerstone therapy in the clinical management of MM, widely used in first-line, second-line, and multi-line treatments.

Darzalex subcutaneous formulation (SC) was approved for marketing in the United States (trade name: Darzalex Faspro) and the European Union (trade name: Darzalex SC) in May and June 2020, respectively. The SC formulation is administered via subcutaneous injection at a fixed dose and can be completed in just 3–5 minutes. In contrast, the intravenous (IV) formulation is administered via infusion over several hours. The approval of the SC formulation marks an important milestone, helping to positively transform the lives of patients with multiple myeloma (MM) who rely on Darzalex treatment.

The approval of this new indication is based on data from the Phase III ANDROMEDA study. This is the first randomized Phase III study investigating the subcutaneous formulation of Darzalex (Darzalex Faspro) as first-line treatment for patients with newly diagnosed light-chain (AL) amyloidosis, evaluating the efficacy and safety of the Darzalex plus bortezomib, cyclophosphamide, and dexamethasone combination regimen (D-VCd) versus the bortezomib, cyclophosphamide, and dexamethasone regimen (VCd). The VCd regimen is the newDiagnosisCommon Treatment Regimens for Adult Patients with AL Amyloidosis.

Data show that,Compared with the VCd treatment group, the D-VCd treatment group demonstrated a threefold increase in the rate of hematologic complete response (hemCR: 42% vs. 13%, p < 0.0001) and sustained reduction in disease markers, indicating a deep hematologic response.Furthermore, the D-VCd group demonstrated higher overall hematologic response rates (92% vs. 77%) and very good partial response or better rates (≥VGPR: 79% vs. 49%) compared with the VCd group. Compared with the VCd regimen, the D-VCd regimen also prolonged major organ deterioration–progression-free survival (MOD-PFS) and event-free survival (EFS). In this study, the safety profile of the combination therapy was consistent with that of subcutaneous Darzalex or VCd.

Light Chain (AL) Amyloidosis is a rare, potentially fatal multisystem disease that occurs when the bone marrow produces abnormal antibody fragments known as light chains (AL). These light chains aggregate to form amyloid fibrils, which deposit in tissues and vital organs, interfering with normal organ function. As the disease progresses, multiple organs—including the heart, kidneys, gastrointestinal tract, liver, and nervous system—gradually deteriorate in many patients. Due to multi-organ involvement (particularly cardiac involvement) in the advanced stages, AL amyloidosisDiagnosisDiagnosis is often delayed, and the prognosis is poor. The median survival of patients with AL amyloidosis is estimated to range from 6 months to 3 years, depending on the patient population and the data source. Currently, there are no approved therapies for this devastating disease.

Darzalex is the first CD38-mediated, cytolytic antibody drug approved globally, with broad-spectrum killing activity. It can target and bind to the CD38 molecule, a transmembrane extracellular enzyme highly expressed on the surface of multiple myeloma cells and various solid tumor cells. Through multiple immune-mediated mechanisms of action, it induces rapid death of tumor cells, including complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP), as well as throughApoptosis(apoptosis). In addition, Darzalex has also been shown to targetTumorImmunosuppressive cells in the microenvironment thereby exhibit immunomodulatory activity.

Darzalex was first approved for marketing in November 2015, with sales reaching $2.998 billion in 2019. Currently, the drug has been approved in many countries worldwide for first-line, second-line, and multiple-line treatment of multiple myeloma.

In China, Darzalex (Zhaoke®, daratumumab) was approved for marketing in October 2019. The drug is indicated as monotherapy for adult patients with relapsed and refractory multiple myeloma, specifically those who have received prior therapies including proteasome inhibitors and immunomodulatory agents and experienced disease progression during their last treatment. As the first CD38 monoclonal antibody targeted therapy approved in China, this innovative regimen is poised to redefine the treatment landscape for multiple myeloma domestically. (Bioon.com)

Original Source: DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) Becomes the FirstFDA-approved Treatment for Patients with Newly Diagnosed Light Chain (AL) Amyloidosis