Darzalex Nears New Indication Approval for First-Line Treatment of Transplant-Eligible Multiple Myeloma

Original: Dopine

On September 26, the FDA will issue a review decision on the supplemental Biologics License Application (sBLA) for Darzalex (daratumumab) in combination with standard of care (bortezomib + lenalidomide + low-dose dexamethasone, VTd) as first-line treatment for patients with multiple myeloma (MM) who are eligible for autologous stem cell transplantation (ASCT). If approved, Darzalex will secure another first-line therapy indication in the MM treatment landscape, providing Johnson & Johnson with new growth momentum.

Related Reading: 《CTTQ vs. Yangtze River! Who Will Secure the First Generic Approval for Pomalidomide, a Blockbuster Multiple Myeloma Drug with $2.04 Billion in Annual Sales?》

Darzalex is the first humanized immunoglobulin G1 (IgG1) monoclonal antibody approved worldwide that targets CD38 molecules on the surface of tumor plasma cells. It exhibits broad-spectrum cytotoxic activity and induces rapid tumor cell death through multiple immune-mediated mechanisms, including complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and apoptosis. Furthermore, Darzalex has been demonstrated to exhibit immunomodulatory activity by targeting immunosuppressive cells within the tumor microenvironment.

Darzalex was initially developed by the Danish pharmaceutical company Genmab. In 2012, Johnson & Johnson secured exclusive global rights to the drug through a $1.1 billion agreement with Genmab. As a key product in Johnson & Johnson’s portfolio, Darzalex holds potential not only for treating multiple myeloma (MM) but also for other cancers characterized by high CD38 expression, including diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), plasma cell leukemia (PCL), acute myeloid leukemia (AML), follicular lymphoma (FL), and mantle cell lymphoma (MCL). In January of this year, Bristol Myers Squibb (BMS) and Johnson & Johnson entered into a strategic collaboration to investigate the combination of the PD-1 immunotherapy Opdivo with Darzalex for the treatment of hematologic malignancies and various solid tumors, including multiple myeloma (MM), non-small cell lung cancer (NSCLC), pancreatic cancer, colorectal cancer (CRC), triple-negative breast cancer (TNBC), and head and neck cancer.

Since its launch in 2015, Darzalex has secured multiple indications in the treatment of multiple myeloma (MM), expanding from its initial use as a fourth-line therapy to first-line therapy, as detailed below:

In May 2013, the FDA granted daratumumab Breakthrough Therapy designation for the treatment of MM.

November 2015: As a monotherapy for patients with multiple myeloma (MM) who have previously received at least three prior therapies (fourth-line therapy).

2016/11 Darzalex in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for patients with multiple myeloma (MM) who have received at least one prior therapy (second-line treatment).

June 2017: Darzalex in combination with pomalidomide and dexamethasone for patients with multiple myeloma (MM) who have previously received at least two prior therapies, including lenalidomide and a proteasome inhibitor (third-line therapy).

November 2017: Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson, submitted a supplemental Biologics License Application (sBLA) to the FDA for Darzalex in combination with bortezomib, melphalan, and prednisone for the treatment of newly diagnosed multiple myeloma (MM) patients who are ineligible for autologous stem cell transplantation (ASCT).

May 2018: Darzalex in combination with bortezomib, melphalan, and prednisone for adult patients with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplantation (ASCT) (first-line therapy).

March 2019: Johnson & Johnson submitted a supplemental Biologics License Application (sBLA) to the FDA for Darzalex in combination with bortezomib, thalidomide, and dexamethasone as first-line treatment for newly diagnosed multiple myeloma (MM) patients eligible for autologous stem cell transplantation (ASCT).

Johnson & Johnson Submits Supplemental Biologics License Application (sBLA) to FDA for Darzalex in Combination with Lenalidomide and Dexamethasone as First-Line Treatment for Newly Diagnosed Multiple Myeloma Patients Ineligible for ASCT

Since its market launch, Darzalex’s sales increased year over year from 2016 to 2018 (see table below), although the growth rate in 2018 was significantly lower than that in 2017. However, with the approval of Darzalex as a first-line therapy for multiple myeloma (MM), its performance in 2019 is expected to be strong; sales in the first half of the year alone already reached USD 1.403 billion. Moreover, in July of this year, the National Medical Products Administration (NMPA) granted conditional approval for the import registration application of daratumumab injection, indicated for monotherapy in adult patients with relapsed and refractory multiple myeloma (including those who have previously received a proteasome inhibitor and an immunomodulatory agent and experienced disease progression during or after their last treatment). Meanwhile, indications are being expanded in the European market. It is estimated that Darzalex’s global sales in 2019 will easily surpass USD 3 billion. EvaluatePharma has previously projected that Darzalex’s global sales could reach USD 6.033 billion by 2024, and some analysts suggest that Darzalex has the potential to exceed USD 10 billion.

Multiple Myeloma and Its Therapeutic Agents

Multiple Myeloma (MM) is a hematologic malignancy characterized by the abnormal proliferation of plasma cells in the bone marrow. Only 25% of patients survive more than 5 years after receiving chemotherapy. Its incidence ranks second only to non-Hodgkin lymphoma, making it the third most common hematologic cancer worldwide, with approximately 114,000 new cases annually. Treatment modalities for MM include chemotherapy, radiotherapy, bone marrow transplantation, and supportive care.

In recent years, with the rapid advancement of diagnostic and therapeutic technologies as well as drug development, the pharmacological landscape for the treatment of multiple myeloma (MM) has undergone significant changes. Currently, the U.S. Food and Drug Administration (FDA) has approved multiple novel agents for MM therapy, which primarily fall into four major categories: proteasome inhibitors (e.g., bortezomib, carfilzomib, ixazomib), immunomodulatory drugs (e.g., lenalidomide, thalidomide, pomalidomide), monoclonal antibodies (e.g., daratumumab, elotuzumab), and histone deacetylase inhibitors (e.g., panobinostat). Details are provided in the table below:

Among the aforementioned drugs, lenalidomide, pomalidomide, and daratumumab are considered blockbuster agents in the field of multiple myeloma (MM) treatment, with global sales in 2018 reaching $9.685 billion, $2.04 billion, and $2.025 billion, respectively, thereby securing their places among the top 100 global pharmaceutical products by sales in 2018. It is anticipated that market competition in the MM sector will intensify as research into these agents deepens.

References:

[1]Janssen Seeks Expanded Use of DARZALEX (daratumumab) Combination Therapy for Newly Diagnosed, Transplant Eligible Patients with Multiple Myeloma

[2] Janssen Submits Application to U.S. FDA to Expand Indication for DARZALEX®(daratumumab) Combination Therapy for Patients with Newly Diagnosed Multiple Myeloma who are Transplant Ineligible