Janssen Submits Two New NDA Applications in China for CD38-Targeting Daratumumab

From: Pharma Insight

On July 3, the latest public announcement from the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration revealed that Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson, has submitted two new marketing applications for additional indications of its CD38 monoclonal antibody, daratumumab injection, in China. Last July, the drug received conditional approval in China for use as monotherapy in adult patients with relapsed and refractory multiple myeloma (MM). According to Johnson & Johnson’s financial reports, the product achieved sales of nearly $3 billion in 2019, solidifying its status as a bona fide blockbuster drug.

Source: CDE Official Website

According to the Janssen announcement, daratumumab is the first fully human monoclonal antibody targeting CD38 approved globally and in China. It specifically recognizes CD38, which is highly expressed on malignant plasma cells in multiple myeloma, with high affinity, thereby inducing tumor cell death through various immune-mediated mechanisms. Since its launch in 2015, daratumumab has received multiple approvals from the U.S. FDA to expand its indications for the treatment of patients with multiple myeloma (MM). The details are as follows:

In November 2015, the FDA approved the anticancer drug daratumumab for the treatment of patients with multiple myeloma (MM).

In November 2016, the FDA approved daratumumab in combination with immunomodulatory agents (IMiDs) lenalidomide and dexamethasone, or with proteasome inhibitors (PIs) bortezomib and dexamethasone, for the treatment of multiple myeloma (MM) in patients who have received at least one prior therapy.

In June 2017, the FDA approved daratumumab in combination with pomalidomide and dexamethasone for the treatment of patients with relapsed multiple myeloma (MM) who are refractory to lenalidomide and proteasome inhibitors (PIs). Studies have shown that the overall response rate (ORR) with this novel combination therapy reached 59.2% in this patient population.

In May 2018, the FDA approved daratumumab 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).

In June 2019, the FDA approved daratumumab in combination with lenalidomide and dexamethasone for the treatment of newly diagnosed multiple myeloma (MM) patients who are ineligible for autologous stem cell transplantation (ASCT). Compared with standard therapy, this combination regimen reduces the risk of disease progression or death by 44%.

In September 2019, the FDA approved daratumumab in combination with bortezomib, thalidomide, and dexamethasone as a first-line treatment for newly diagnosed multiple myeloma (MM) patients eligible for autologous stem cell transplantation (ASCT). This also means that daratumumab-based combination therapy is an option for these patients regardless of their eligibility for ASCT.

In May 2020, the FDA approved the subcutaneous formulation of daratumumab, Darzalex Faspro, for the treatment of patients with multiple myeloma (MM). The new combination product can be administered in approximately 3–5 minutes, representing a significant reduction in administration time compared to daratumumab monotherapy.

As can be seen, daratumumab completed its leap from last-line to first-line therapy in the United States within four years, while continually setting new benchmarks for efficacy in the treatment of patients with multiple myeloma (MM). According to Johnson & Johnson’s 2019 annual report, the product achieved sales of $2.998 billion in 2019, underscoring the urgent clinical need among patients.

In China, daratumumab was first submitted for clinical trial application and accepted in September 2013. To date, 13 clinical trial applications for this product have been submitted in China. According to the Drug Clinical Trial Registration and Information Publicity Platform, seven clinical studies have been registered in China for this product. The indications include multiple myeloma (MM), relapsed or refractory nasal-type natural killer/T-cell lymphoma, and systemic light-chain amyloidosis. Owing to its innovative mechanism of action and significant clinical benefits, daratumumab has also been granted priority review and special approval status by the National Medical Products Administration (NMPA).

In July 2019, the drug received conditional approval in China for use as monotherapy in adult patients with relapsed and refractory multiple myeloma (MM), including those who had previously received at least one proteasome inhibitor (PI) and one immunomodulatory drug (IMiD) and experienced disease progression during or after their last treatment. The brand name is Zhaokex.

▲ Clinical Development Status of Daratumumab in China (Screenshot source: www.chinadrugtrials.org)

Multiple myeloma is a malignant hematologic cancer caused by the malignant transformation of plasma cells in the bone marrow. Symptoms include fractures, bone pain, fatigue, renal impairment, and infections, which severely impact patients’ health and survival. Currently, treatment regimens primarily consist of chemotherapy, immunomodulatory drugs (IMiDs) such as lenalidomide, and/or proteasome inhibitors (PIs) such as bortezomib, with or without autologous stem cell transplantation (ASCT).

Studies have shown that the median overall survival (OS) for patients with relapsed and refractory multiple myeloma (MM) is only 9 months after receiving multiple lines of treatment with proteasome inhibitors (PIs) and immunomodulatory agents. The approval of daratumumab has provided a new therapeutic option for these patients. Clinical studies have demonstrated that monotherapy with this drug in MM patients who have previously undergone multiple lines of treatment can extend the median OS to 20 months, with an overall response rate of 31%.

Daratumumab has submitted two new indication marketing applications in China, which also means that the drug is expected to expand into new indications in China, thereby benefiting more patients. We wish this product a smooth subsequent development and registration process.

References:

[1] Center for Drug Evaluation, National Medical Products Administration of China. Retrieved July 3, 2020, from http://www.cde.org.cn/news.do?method=changePage&pageName=service&frameStr=21#

[2] U.S. Food and Drug Administration Approves DARZALEX FASPRO™ (daratumumab and hyaluronidase-fihj), a New Subcutaneous Formulation of Daratumumab in the Treatment of Patients with Multiple Myeloma. Retrieved 2020-05-04, from https://www.janssen.com/us-food-and-drug-administration-approves-darzalex-fasprotm-daratumumab-and-hyaluronidase-fihj-new

[3] Janssen Announces DARZALEX® (daratumumab) U.S. FDA Approval for Newly Diagnosed Patients with Multiple Myeloma who are Transplant Ineligible

[4] Genmab Announces U.S. FDA Approval of DARZALEX® (daratumumab) in Combination with Bortezomib, Thalidomide and Dexamethasone for Frontline Multiple Myeloma, Retrieved September 26, 2019, from http://www.globenewswire.com/news-release/2019/09/26/1921458/0/en/Genmab-Announces-U-S-FDA-Approval-of-DARZALEX-daratumumab-in-Combination-with-Bortezomib-Thalidomide-and-Dexamethasone-for-Frontline-Multiple-Myeloma.html

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