Daratumumab Submits New Drug Application in China Following $4.19 Billion Global Sales in 2020

At the beginning of the new year, the Class 3.1 registration application for daratumumab, submitted by Xian Janssen, a subsidiary of Johnson & Johnson, in China was accepted by the Center for Drug Evaluation (CDE). According to Johnson & Johnson’s financial report, global sales of daratumumab reached $4.19 billion in 2020, representing a year-on-year increase of 39.8%.

Daratumumab (Darzalex) is a humanized anti-CD38 IgG1 monoclonal antibody that Johnson & Johnson acquired from Genmab for $1.1 billion. It binds to CD38 expressed on tumor cells and induces tumor cell apoptosis through multiple immune-mediated mechanisms, including complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and Fcγ receptor-mediated effects.

In November 2015, daratumumab was approved by the FDA in combination with lenalidomide and dexamethasone, or with bortezomib and dexamethasone, for the treatment of patients with multiple myeloma (MM) who had received at least one prior therapy, becoming the first CD38-targeted monoclonal antibody approved globally. In May 2016, the drug was approved in the European Union for the treatment of relapsed or refractory (R/R) MM. Subsequently, Darzalex has been approved in numerous countries and regions worldwide for multi-line, second-line, and first-line treatment of MM, establishing itself as a mainstream clinical therapy for MM. Furthermore, Johnson & Johnson introduced a split-dosing regimen for Darzalex (dividing the initial intravenous infusion from a single administration into two consecutive daily infusions, effectively shortening the duration of the first infusion) and a subcutaneous formulation (which utilizes Halozyme’s ENHANZE drug delivery technology and contains recombinant human hyaluronidase PH20 [rHuPH20], reducing treatment time from several hours to 3–5 minutes; marketed under the brand name Darzalex Faspro).

In addition to treating MM, the subcutaneous formulation of daratumumab was approved by the FDA in January this year for use in combination with bortezomib, cyclophosphamide, and dexamethasone (i.e., the D-VCd regimen) for the treatment of adult patients with newly diagnosed light-chain (AL) amyloidosis, becoming the first and only drug approved for the treatment of AL amyloidosis.

Since its launch, Darzalex’s global sales have risen year by year, reaching $4.19 billion in 2020. Notably, in 2020, Darzalex surpassed Remicade (infliximab) and Imbruvica (ibrutinib) to become Johnson & Johnson’s second-largest blockbuster product (with Stelara [ustekinumab] ranking first).

In China, daratumumab injection was approved by the NMPA in July 2019 for use as monotherapy in adult patients with relapsed and refractory multiple myeloma, including those who had previously received at least one proteasome inhibitor and one immunomodulatory agent and demonstrated disease progression during or after their last treatment. The brand name is Zhaoke.

Furthermore, according to the official website of the Center for Drug Evaluation (CDE), a marketing application for daratumumab injection has also been submitted in China for the treatment of adult patients with multiple myeloma who have received at least one prior line of therapy, in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone. The relevant acceptance numbers are JXSS2000019/20. Moreover, the subcutaneous formulation of daratumumab has also been submitted for marketing approval in China, with the indicated indication being primary light-chain amyloidosis. On this occasion, a Class 3.1 registration application for daratumumab injection has been submitted in China; the specific details of the submission remain to be officially disclosed.

According to the Insight database, the latest winning bid prices for daratumumab in various regions across China are CNY 19,710.00 per vial (400 mg/20 mL) and CNY 5,460.00 per vial (100 mg/5 mL). Based on the product labeling, assuming one vial per administration, a total of 44 vials are required over 52 weeks in a year. Consequently, the annual treatment cost is substantial, far exceeding the affordability level of the general population.

Image source: DXY

Of note to the public, Henlius Biotech of China has begun to lay out its strategy in the daratumumab biosimilar market. Its daratumumab biosimilar, HLX15 (recombinant fully human anti-CD38 monoclonal antibody injection), has been approved for clinical trials, with multiple myeloma (MM) as the indication. It is reported that HLX15 is a fully human anti-CD38 IgG1κ monoclonal antibody independently developed by Henlius. In accordance with the Technical Guidelines for the Research and Evaluation of Biosimilars (Trial) issued by the National Medical Products Administration (NMPA) and the Guideline on Similar Biological Medicinal Products issued by the European Medicines Agency (EMA), Henlius has conducted head-to-head pharmaceutical analyses and comparative in vitro and in vivo pharmacological studies between HLX15 and the originator daratumumab, following the principles of stepwise comparison and similarity assessment. The study results demonstrated a high degree of similarity between HLX15 and the originator daratumumab.

Furthermore, it is worth noting that competing agents in the same class as daratumumab have already been approved abroad. In March 2020, the FDA approved Sanofi’s CD38 antibody Sarclisa (isatuximab-irfc) in combination with pomalidomide and dexamethasone for adult patients with relapsed/refractory multiple myeloma (R/RMM) who had previously received at least two prior therapies, including lenalidomide and a proteasome inhibitor. Moreover, the Phase III clinical trial of Sarclisa in combination with carfilzomib and dexamethasone, a standard-of-care regimen for R/RMM, also yielded positive results. Analysts at Jefferies, a Wall Street investment bank, project that annual peak sales of Sarclisa are expected to exceed $1 billion following its market launch.