EU Approves Janssen's Darzalex SC (Daratumumab and Hyaluronidase-fihj) for AL Amyloidosis and Relapsed/Refractory Multiple Myeloma with 3–5 Minute Subcutaneous Administration
Jun 23, 2021 03:26
CST Updated
03:26
Johnson & Johnson
Healthcare Product Manufacturers, Health Service Providers
European Commission
The European Commission, abbreviated as the EU Commission, is a supranational body under the European Union. Within the EU political system, the European Commission primarily undertakes executive tasks, thus being roughly equivalent to the government in a national system. However, the European Commission has other functions as well. In particular, except for the few circumstances specified in the treaties, the European Commission is the only institution with legislative power in the EU legislative process.
June 22, 2021 /BioonBIOON/ -- Recently, the European Commission (EC) has approved two marketing authorization applications for Johnson & Johnson's (JNJ) subcutaneous (SC) formulation of daratumumab—Darzalex SC (daratumumab and hyaluronidase-fihj): (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 have previously received one regimen containing a proteasome inhibitor and lenalidomide and are refractory to lenalidomide, or patients who have previously received at least two regimens containing lenalidomide and a proteasome inhibitor and have demonstrated disease progression during or following the last therapy.
In the United States, the brand name for the Darzalex SC formulation is Darzalex Faspro.Darzalex SC/Darzalex Faspro is administered at a fixed dose via subcutaneous injection and takes only 3-5 minutes to complete.. However, the Darzalex intravenous (IV) formulation is administered via intravenous infusion, which typically takes several hours. In the United States and the European Union,Darzalex SC/Darzalex Faspro is the first and only approved drug for the treatment of AL amyloidosis, and is indicated for first-line treatment of newDiagnosisadult patients with AL amyloidosis.
In August 2012, Genmab granted Janssen Biotech, Inc., a Johnson & Johnson company, an exclusive worldwide license to develop, manufacture, and commercialize daratumumab. The development of the Darzalex SC/Darzalex Faspro formulations utilizes Halozyme’s ENHANZE® drug delivery technology, and the formulation contains recombinant human hyaluronidase PH20 (rHuPH20).
Light chain amyloidosis (Image source: haematologica.org)
AL amyloidosis is a rare and potentially fatal multisystem disease that occurs when an insoluble protein called amyloid accumulates in tissues and organs, interfering with normal tissue and organ function. The broad and nonspecific nature of symptoms associated with AL amyloidosis can lead toDiagnosisDelayed treatment and deterioration of organ function. Without treatment, the average survival period is 12 to 18 months, and only about 6 months for patients with severe cardiac dysfunction.
The European Commission’s approval of the D-VCd regimen for the treatment of AL amyloidosis is based on data from the Phase III ANDROMEDA study. This is the first randomized Phase III 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 regimens for adult patients with AL amyloidosis. Data show that,Compared with the VCd treatment group, the hematologic complete response rate was significantly higher in the D-VCd treatment group (hemCR: 53.3% vs 18.1%, p < 0.0001).. Overall, the safety profile of D-VCd was consistent with that previously observed for each individual drug.
Multiple Myeloma (Image from: cancer.gov)
Multiple myeloma (MM), despite significant therapeutic advances over the past decade, remains a complex hematologic malignancy, and the management of relapsed or refractory disease is a particularly challenging area.
The EC's approval of the D-Pd regimen for the treatment of MM was based on data from the Phase 3 APOLLO study (MMY3013). The study enrolled a total of 304 patients with relapsed/refractory multiple myeloma (r/r MM) who had received at least one prior line of therapy, had previously been treated with lenalidomide and a proteasome inhibitor, and had documented 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 group and the Pd group was 12.4 months and 6.9 months, respectively. In addition,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 negativity rate (9% vs 2%).. The safety profile of D-Pd is consistent with the known safety profiles of Darzalex SC and Pd.
Darzalex (Zhaoke®): China's First CD38-Targeted Monoclonal Antibody, Redefining Myeloma Treatment
Darzalex is the first approved fully human monoclonal antibody targeting CD38, featuring a unique and innovative mechanism of action that directly and specifically binds to CD38, a key immunotherapeutic target on the surface of myeloma cells, inducing myeloma cell death through multiple mechanisms to achieve rapid remission.
Darzalex was launched in 2015 and has since become a backbone therapy for the clinical treatment of multiple myeloma (MM), widely used across first-line, second-line, and multiple lines of treatment.
In China, Darzalex (Zhaoke®, daratumumab injection) was approved in July 2019, becoming the first approved fully human monoclonal antibody targeting CD38 in China., the drug is approved for use as monotherapy in adult patients with relapsed and refractory multiple myeloma, specifically: patients who have previously received treatment including a proteasome inhibitor and an immunomodulatory agent and have demonstrated disease progression on or after the last therapy.
In April 2021, Darzalex received additional approval in China for use in combination with lenalidomide and dexamethasone or with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior line of therapy. The approval of this indication will further fill the treatment gap for relapsed or refractory multiple myeloma in China, bringing more innovative options to patients at earlier stages of treatment. (Bioon.com)