Janssen's Darzalex (Daratumumab) Subcutaneous Formulation Demonstrates Success in Phase III APOLLO Trial, Significantly Extending Progression-Free Survival in Relapsed or Refractory Multiple Myeloma with Just 3–5 Minutes Administration Time

August 02, 2020 News /BioValleyBIOON/ -- Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson (JNJ), and the European Myeloma Network (EMN) recently announced positive results from the Phase III APOLLO study (MMY3013, NCT03180736) evaluating the subcutaneous (SC) formulation of Darzalex (daratumumab) for the treatment of relapsed or refractory multiple myeloma (R/R MM).

Darzalex is the first CD38-mediated, cytolytic antibody drug approved globally, and it is in the United StatesFDAThe first monoclonal antibody approved for the treatment of multiple myeloma (MM), its intravenous (IV) formulation was launched in 2015 and has been approved in multiple countries worldwide for first-line, second-line, and multi-line treatment of MM, currently becoming a backbone therapy in clinical practice for MM. Its 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 of this year, respectively.

The SC formulation is administered via fixed-dose subcutaneous injection, requiring only 3–5 minutes for completion. In contrast, the IV formulation is administered via intravenous infusion, which takes several hours. The approval and market launch of the SC formulation mark a significant milestone that will help positively transform the lives of patients with multiple myeloma (MM) who rely on Darzalex treatment.

Clinical data demonstrate that, compared with the intravenous (IV) formulation of Darzalex, the subcutaneous (SC) formulation of Darzalex provides consistent efficacy and pharmacokinetics, along with a similar safety profile. It significantly reduces treatment time (from several hours to 3–5 minutes) and lowers the incidence of systemic administration-related reactions (ARRs) by two-thirds (13% vs. 44%).

APOLLO is a randomized, open-label, multicenter study that enrolled 304 patients with relapsed/refractory multiple myeloma (R/R MM) who had previously been treated with lenalidomide (an immunomodulatory drug [IMiD]) and a proteasome inhibitor (PI). In the study, patients were randomized in a 1:1 ratio to two groups receiving either daratumumab subcutaneous (Darzalex SC) in combination with pomalidomide and dexamethasone (Pd), or Pd alone. Under the initial study design, patients in the Darzalex + Pd arm received intravenous (IV) daratumumab. Following a protocol amendment, all newly enrolled participants in the experimental arm received the subcutaneous (SC) formulation of daratumumab. The primary endpoint of the study was progression-free survival (PFS). The study was conducted in Europe under the auspices of Janssen, the European Myeloma Network (EMN), and the Dutch Adult HematologyTumorconducted in accordance with the protocols of the HOVON Working Group.

The results showed that the study met its primary endpoint:Compared with the Pd group, the Darzalex + Pd group showed significant improvement in PFS.Regarding safety, overall, the safety profile of the Darzalex SC+Pd combination regimen was consistent with that of each individual drug in the regimen.

In 2012, Janssen obtained the exclusive global license from Genmab to develop, manufacture, and commercialize daratumumab. The company intends to discuss these data with regulatory authorities in preparation for regulatory submissions and plans to present at upcoming medicalMeetingpublish the complete data on.

The APOLLO study was designed to confirm the results of the Phase I EQUULEUS (MMY1001) study, which evaluated the intravenous (IV) Darzalex + Pd regimen in the same indication. In June 2017, the United StatesFDABased on the results of the EQUULEUS study, approval was granted for the use of Darzalex in combination with Pd for the treatment of patients with relapsed/refractory multiple myeloma (R/R MM), specifically those who had previously received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI).

Multiple Myeloma (MM) is an incurable blood cancer that originates in the bone marrow and is characterized by the excessive proliferation of plasma cells. It is the third most common blood cancer in the United States, second only toLeukemiaand lymphoma. It is estimated that in 2018, there were 160,000 people worldwide who wereDiagnosis...were diagnosed with the disease, and 106,000 people died from it. Although some patients with multiple myeloma (MM) are entirely asymptomatic, most patients are diagnosed due to associated symptoms, including: bone problems, low blood cell counts, hypercalcemia, kidney problems, or infections.etc.

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, inducing rapid death of tumor cells through multiple immune-mediated mechanisms of action, including complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and throughApoptosis(apoptosis). In addition, Darzalex has also been shown to targetTumorImmunosuppressive cells in the microenvironment thus 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 multi-line treatment of multiple myeloma, although the specific approved indications vary by country. In the United States, the drug has been approved for: (1) November 2015, as a monotherapy for adult patients with multiple myeloma (MM) who have previously received at least three prior therapies (including a proteasome inhibitor [PI] and an immunomodulatory agent [IMiD]) or who are double-refractory to PIs and IMiDs; (2) November 2016, in combination with lenalidomide and dexamethasone, or in combination with bortezomib and dexamethasone, for adult patients with MM who have received at least one prior therapy; (3) June 2017, in combination with pomalidomide and dexamethasone, for adult patients with MM who have previously received at least two prior therapies (including lenalidomide and a PI); (4) May 2018, in combination with bortezomib, melphalan, and prednisone, for patients ineligible for autologousStem Cellsadult patients with newly diagnosed multiple myeloma (MM) eligible for autologous stem cell transplantation (ASCT), this approval makes Darzalex the first therapy approved for the treatment of newly diagnosed MMMonoclonal Antibody Drugs(5) In June 2019, in combination with lenalidomide and dexamethasone, for adult patients with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplantation (ASCT). (6) In September 2019, in combination with bortezomib, thalidomide, and dexamethasone, for adult patients with newly diagnosed MM who are eligible for ASCT. This approval made Darzalex the first biologic agent approved for use in patients with newly diagnosed MM who are eligible for ASCT.

In February 2019, a split-dosing regimen for Darzalex was also approved by the U.S.FDAApproved. This protocol will allow healthcare professionals to choose, as needed, when treating MM patients, to split the initial intravenous infusion of Darzalex from a single one-time infusion into divided intravenous infusions over two consecutive days.

In May 2020, the subcutaneous formulation of Darzalex (Darzalex Faspro) was approved in the United StatesFDAApproved, covering four regimens across five therapeutic indications, including for patients with newly diagnosed multiple myeloma (MM), MM patients ineligible for autologous stem cell transplantation (ASCT), and patients with relapsed or refractory MM.

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 previously received treatments 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 expected to redefine the treatment landscape for multiple myeloma domestically. (Bioon.com)

Original Source: Genmab Announces European Myeloma Network and Janssen Achieve Positive Topline Results from Phase 3 APOLLO Study of Daratumumab in Combination with Pomalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma