First-Ever Therapy for Light Chain (AL) Amyloidosis: Darzalex Faspro Shows Sustained Hematologic Complete Response in Long-Term Data

May 27, 2021 /BioonBIOON/ -- Janssen Pharmaceuticals, a Johnson & Johnson (JNJ) company, recently announced Darzalex Faspro (daratumumab and hyaluronidase-fihj, daratumumab-hyaluronidase) for the treatment of newDiagnosislatest results from the Phase 3 ANDROMEDA study in patients with light chain (AL) amyloidosis.Long-term results with a median follow-up of 20.3 months showed that, compared with patients treated with the VCd regimen (bortezomib + cyclophosphamide + dexamethasone), the hematologic complete response rate (hemCR) in patients treated with the D-VCd regimen (Darzalex Faspro + bortezomib + cyclophosphamide + dexamethasone) remained significantly higher.

AL amyloidosis is a rare and potentially fatal multisystem disease that occurs when an insoluble protein called amyloid accumulates in tissues and organs, disrupting normal tissue and organ function. The VCd regimen is a newDiagnosiscommonly used treatment regimen for adult patients with AL amyloidosis.

Darzalex Faspro is Johnson & Johnson's blockbuster CD38 monoclonal antibody.Monoclonal antibody drugsThe subcutaneous (SC) formulation of Darzalex (Zhaoke®, generic name: daratumumab). In January 2021, Darzalex Faspro received USFDAAccelerated approval, in combination with bortezomib, cyclophosphamide, and dexamethasone (D-VCd regimen), for the treatment of newlyDiagnosisadult patients with light chain (AL) amyloidosis. It is worth noting that,Darzalex Faspro is the first and only drug for the treatment of AL amyloidosis.This indication was granted accelerated approval based on response data. Previously published data from the ANDROMEDA study demonstrated that, compared with patients receiving the standard-of-care VCd regimen, those receiving the D-VCd regimen achieved a significantly higher hematologic complete response rate (hemCR: 42% vs 13%, p<0.0001) and a sustained reduction in disease markers, indicating a deep hematologic response.

Efstathios Kastritis, an ANDROMEDA study investigator and Professor of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine, Greece, stated: “Patients with AL amyloidosis, including those with organ dysfunction, often have a poor prognosis, with up to 30% of patients dying within the first year following diagnosis. The long-term results of the ANDROMEDA study demonstrate sustained overall deep hematologic responses, further establishing subcutaneous daratumumab as part of the new standard of care for patients with AL amyloidosis. I am also pleased to see additional study data showing cardiac and renal responses in these patients.”

The ANDROMEDA study is investigating Darzalex Faspro as first-line treatment for patients with newly diagnosed light-chain (AL) amyloidosis, evaluating the efficacy and safety of the D-VCd regimen (n=193) versus the VCd regimen (n=188). The VCd regimen is a newDiagnosiscommonly used treatment regimens for adult patients with AL amyloidosis.

Data show that at a median follow-up of 11.4 months, the hematologic complete response rate was significantly higher in the D-VCd treatment group compared with the VCd treatment group.（hemCR：53% vs 18%）, the response rate increased and remained significantly higher at a median follow-up of 20.3 months（hemCR：59% vs 19%）、A higher proportion of patients achieved a very good partial response or better (≥VGPR: 79% vs. 50%). The median time from randomization to VGPR was shorter in the D-VCd treatment group than in the VCd group.

Among patients with a cardiac response, compared with the VCd treatment group (n=117),The cardiac response rate in the D-VCd treatment group (n=118) increased from 42% at 12 months to 57%, while that in the VCd treatment group increased from 22% at 12 months to 28%.

Among renal responders, compared with the VCd treatment group (n=113),In the D-VCd treatment group (n=117), the renal response rate steadily increased from 54% at 12 months to 57%, while the VCd treatment group remained stable at the 12-month level of 27%.

During long-term follow-up, no new safety signals were observed for Darzalex Faspro. 2 The most commonAdverse Reactions(≥25%) were diarrhea, peripheral edema, constipation, peripheral sensory neuropathy, fatigue, nausea, upper respiratory tract infection, and insomnia. Grade 3 or 4 treatment-emergent adverse events (TEAEs) ≥ included diarrhea, peripheral edema, lymphopenia, neutropenia, pneumonia, syncope, and heart failure. Starting from Cycle 7, no Grade 3 or 4 TEAEs occurred in ≥5% of patients.

Light chain (AL) amyloidosis is a rare, potentially fatal multisystem disease that occurs when the bone marrow produces abnormal antibody fragments called light chains (AL), which aggregate to form amyloid. These amyloid deposits accumulate in tissues and vital organs, impairing 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 (particularly cardiac) involvement in the late stages, AL amyloidosis'sDiagnosisis often delayed, and the prognosis is very poor. The median survival for patients with AL amyloidosis is estimated to be between 6 months and 3 years, depending on the patient population and the data used. Currently, there are no approved treatment regimens for this devastating disease.

Darzalex is the first globally approved CD38-directed cytolytic antibody drug, featuring broad-spectrum cytolytic activity. It can target and bind to the CD38 transmembrane ectoenzyme highly expressed on the surface of multiple myeloma and various solid tumor cells, inducing rapid tumor cell death through multiple immune-mediated mechanisms of action, including complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP), as well as throughApoptosis(apoptosis). In addition, Darzalex has also been demonstrated to targetTumor`thereby exhibiting immunomodulatory activity on immunosuppressive cells in the microenvironment.`

The Darzalex intravenous (IV) formulation was launched in 2015 and has since become a backbone therapy in the clinical treatment of multiple myeloma (MM), widely used in first-line, second-line, and later-line treatments. The Darzalex subcutaneous (SC) formulation received regulatory approval in the United States (brand name: Darzalex Faspro) in May 2020 and in the European Union (brand name: Darzalex SC) in June 2020. Administered as a fixed-dose subcutaneous injection, the SC formulation takes only 3–5 minutes to complete. In contrast, the IV formulation is delivered via intravenous infusion, which requires several hours. The approval of the SC formulation marks a significant milestone, poised to positively transform the lives of the MM patient population reliant on Darzalex therapy.

In China, Darzalex (ZHAOKE®, daratumumab, intravenous formulation) was approved for marketing in October 2019. The drug is indicated as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, specifically: patients who have received prior therapy including a proteasome inhibitor and an immunomodulatory agent and who have demonstrated disease progression on or after their last therapy. Notably,Darzalex is China's first approved CD38-targeted monoclonal antibody drug., this innovative regimen is expected to redefine the treatment of multiple myeloma in China. (Bioon.com)

Source: Updated Data Demonstrate Significant Improvement in Hematologic Complete Response with DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) in Patients with Newly Diagnosed Light Chain (AL) Amyloidosis