Janssen’s DARZALEX® (daratumumab) Subcutaneous Formulation Receives CHMP Positive Opinions for AL Amyloidosis and Relapsed/Refractory Multiple Myeloma in Europe

May 24, 2021 /Bio ValleyBIOON/ -- Janssen Pharmaceuticals, a Johnson & Johnson (JNJ) company, recently announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending the approval of the subcutaneous (SC) formulation of Darzalex (daratumumab): (1) Darzalex SC in combination with bortezomib, cyclophosphamide, and dexamethasone (D-VCd regimen) for the treatment of newlyDiagnosisadult patients with systemic light chain (AL) amyloidosis; (2) Darzalex SC in combination with pomalidomide and dexamethasone (D-Pd), for the treatment of adult patients with multiple myeloma (MM), specifically: patients who are lenalidomide-refractory and have received one prior therapy containing a proteasome inhibitor and lenalidomide, or patients who have received at least two prior therapies containing lenalidomide and a proteasome inhibitor, and have demonstrated disease progression during or following their last therapy.

AL amyloidosis and relapsed multiple myeloma (MM) are both hematologic diseases with unmet treatment needs. AL amyloidosis is a rare and potentially life-threatening condition that occurs when an insoluble protein known as amyloid accumulates in tissues and organs, ultimately leading to organ dysfunction. The wide-ranging and non-specific nature of symptoms associated with AL amyloidosis can lead toDiagnosisDelays lead to the deterioration of organ function, which means that the disease has already progressed by the time treatment is initiated for some patients.In Europe, there are currently no approved treatments for AL amyloidosis.. Without treatment, the average survival time for patients is 12 to 18 months, and only about 6 months for those with severe cardiac impairment.

Multiple myeloma (MM), despite significant therapeutic advances over the past decade, remains a complex hematologic malignancy, and the management of relapsed or refractory disease represents a particularly challenging area. Patient prognosis deteriorates with each relapse, underscoring the critical need for effective treatment regimens.

Saskia De Haes, Vice President of Regulatory Affairs, EMEA at Janssen Pharmaceuticals, said: “The positive CHMP opinion today is an important step forward in enabling us to address the treatment needs of more patients with these complex blood disorders. Darzalex has played a pivotal role in transforming the multiple myeloma treatment landscape, and since its initial approval in 2016, it has been used to treat nearly 190,000 patients. We look forward to leveraging our expertise to deepen our impact in multiple myeloma and to bring transformation to patients with AL amyloidosis, a disease area in urgent need of innovation.”

The CHMP's positive opinion on the AL amyloidosis indication is based on data from the Phase 3 ANDROMEDA study. This is the first randomized Phase 3 study investigating Darzalex SC as first-line treatment for patients with newly diagnosed 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 a newDiagnosiscommonly used treatment regimen in adult patients with AL amyloidosis. Data show that,Compared with the VCd treatment group, patients in the D-VCd treatment group had a significantly higher hematologic complete response rate (hemCR: 53.3% vs. 18.1%, p < 0.0001).Overall, the safety of D-VCd was consistent with the safety of each drug previously observed individually.

The CHMP's positive opinion on D-Pd for the treatment of MM is based on data from the Phase 3 APOLLO study (MMY3013). This study enrolled 304 patients with r/r MM who had received at least one prior line of therapy, including lenalidomide and a proteasome inhibitor, and had confirmed disease progression. The results showed that,Compared with Pd, D-Pd significantly reduced the risk of disease progression or death by 37%.(HR=0.63, p=0.0018). The median progression-free survival (PFS) for the D-Pd and Pd groups was 12.4 months and 6.9 months, respectively. Furthermore, compared with the Pd group, the D-Pd group demonstrated higher response rates, including: overall response rate (ORR: 69% vs 46%), very good partial response (VGPR) or better (51% vs 20%), complete response rate (CR: 25% vs 4%), and minimal residual disease (MRD) negativity rate (9% vs 2%). The safety profile of D-Pd was consistent with the known safety profiles of Darzalex-SC and Pd.

Darzalex is the first CD38-directed cytolytic antibody drug approved globally, possessing broad-spectrum cytolytic activity. It specifically targets and binds to the transmembrane ectoenzyme CD38 molecule, which is 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 shown to targetTumorImmunosuppressive cells in the microenvironment, thereby exhibiting immunomodulatory activity.

Darzalex is the world's first CD38-directed cytolytic monoclonal antibody; its intravenous (IV) formulation was launched in 2015 and has since become a backbone therapy for the clinical treatment of multiple myeloma (MM), widely used in first-line, second-line, and multi-line treatment regimens.

The Darzalex subcutaneous (SC) formulation 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 at a fixed dose via subcutaneous injection and takes only 3 to 5 minutes to complete. In contrast, the intravenous (IV) formulation is administered via intravenous infusion and requires several hours. The approval and launch of the SC formulation mark a significant milestone, helping to positively transform the lives of the multiple myeloma (MM) patient population reliant on Darzalex treatment.

In January 2021, Darzalex Faspro (the US market trade name for Darzalex SC) received USFDAApproved, in combination with bortezomib, cyclophosphamide, and dexamethasone (D-VCd regimen), for the treatment of newlyDiagnosisadult patients with light chain (AL) amyloidosis. Notably, Darzalex Faspro is the first and only drug for the treatment of AL amyloidosis.

In China, Darzalex (Zhaoke®, daratumumab) received marketing approval in October 2019. The drug is indicated as monotherapy for adult patients with relapsed and refractory multiple myeloma, specifically those who have previously received therapy including a proteasome inhibitor and an immunomodulatory agent and have demonstrated disease progression on or after their last treatment. As the first approved CD38 monoclonal antibody targeted therapy in China, this innovative regimen is expected to redefine the treatment landscape for multiple myeloma domestically. (Bioon.com)

Source: Janssen Receives Two Positive CHMP Opinions Recommending Expanded Use of DARZALEX® (daratumumab) Subcutaneous (SC) Formulation for New Indications in Europe