Janssen's Subcutaneous CD38 Monoclonal Antibody Daratumumab Nears Approval in China

By | Pharma Insights

According to the official website of China's National Medical Products Administration (NMPA), the marketing authorization application for daratumumab injection (subcutaneous), a CD38 monoclonal antibody from Janssen, a Johnson & Johnson company, has been updated to "under review," indicating that the drug is expected to be approved in China in the near future. Publicly available information indicates that the subcutaneous formulation of daratumumab can be administered in approximately 3 to 5 minutes, reducing patient administration time from several hours to just a few minutes compared to the intravenous formulation of the product.

Image Source: NMPA Official Website

According to publicly available information, daratumumab is the first fully human monoclonal antibody targeting CD38 to be approved globally and in China, with its intravenous formulation having previously been approved in China. The daratumumab subcutaneous injection (English brand name: Darzalex Faspro) is a fixed-dose combination of daratumumab and recombinant human hyaluronidase PH20 (rHuPH20). Developed by Halozyme Therapeutics utilizing its ENHANZE drug delivery technology, rHuPH20 degrades hyaluronic acid in the body to facilitate the penetration and absorption of subcutaneously administered drugs.

Previously, daratumumab subcutaneous injection has been approved by the U.S. FDA for the treatment of multiple myeloma, light chain (AL) amyloidosis, and other indications.

In November 2020, Janssen submitted a marketing authorization application in China for daratumumab subcutaneous injection. The application was subsequently included in the priority review program by the Center for Drug Evaluation (CDE) under the category of "innovative drugs and improved new drugs for clinically urgently needed shortage medicines, and for the prevention and treatment of major infectious diseases and rare diseases." It is intended for the treatment of patients with primary light-chain amyloidosis.

Image source: CDE official website

In China, primary light-chain amyloidosis has been included in the 《Catalog of the First Batch of Rare Diseases》. This is a rare, life-threatening disease. It occurs when plasma cells in the bone marrow produce abnormal light chains, which form amyloid deposits that accumulate in vital organs, ultimately leading to organ dysfunction. The disease can affect multiple organs in different patient populations, with the most commonly affected being the heart, kidneys, liver, spleen, gastrointestinal tract, and nervous system. Currently, there is an urgent need for new treatment options for these patients.

Studies have shown that daratumumab specifically binds to CD38 with high affinity, which is highly expressed on malignant plasma cells in multiple myeloma, thereby inducing tumor cell death through multiple immune-mediated mechanisms. Although the pathogenesis of immunoglobulin light chain (AL) amyloidosis is fundamentally distinct from that of multiple myeloma, the plasma cells overproducing immunoglobulin light chains also express CD38, enabling their targeted elimination with daratumumab.

Based on data from the phase 3 ANDROMEDA study, which evaluated the efficacy and safety of subcutaneous daratumumab injection in combination with bortezomib, cyclophosphamide, and dexamethasone (VCd regimen) versus the VCd regimen alone, results showed that the hematologic complete response (hemCR) rate in patients receiving the daratumumab combination therapy was more than three times higher than that in patients receiving the VCd regimen alone (42% vs. 13%).

References:

[1] Drug Registration Status Inquiry. Retrieved Oct 8, 2021, from http://sq.nmpa.gov.cn/datasearch_nmpa/schedule/search.jsp?tableId=43&tableName=TABLE43&columnName=COLUMN464,COLUMN475&title1=Drug Registration Status Inquiry

[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] Genmab Announces Positive Topline Results in Phase III ANDROMEDA Study of Daratumumab in Light-chain (AL) Amyloidosis. Retrieved 2020-05-29, from http://www.globenewswire.com/news-release/2020/05/28/2040461/0/en/Genmab-Announces-Positive-Topline-Results-in-Phase-III-ANDROMEDA-Study-of-Daratumumab-in-Light-chain-AL-Amyloidosis.html

[4] DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) Becomes the First FDA-Approved Treatment for Patients with Newly Diagnosed Light Chain (AL) Amyloidosis. Retrieved Jan 15, 2021, from https://www.janssen.com/darzalex-faspror-daratumumab-and-hyaluronidase-fihj-becomes-first-fda-approved-treatment-patients

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