Darzalex (daratumumab)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company:

Approval Status:

Approved November 2015

Specific Treatments:

multiple myeloma

Therapeutic Areas

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General Information

Darzalex (daratumumab) is a human CD38-directed monoclonal antibody.

Darzalex is specifically indicated for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent.

Darzalex is supplied as a solution for intravenous infusion. The recommended dose of Darzalex is 16 mg/kg body weight administered as an intravenous infusion according to the following dosing schedule:

Schedule: Weekly - Weeks 1 to 8

Schedule: Every two weeks - Weeks 9 to 24

Schedule: Every four weeks - Week 25 onwards until disease progression.

If a planned dose of Darzalex is missed, administer the dose as soon as possible and adjust the dosing schedule accordingly, maintaining the treatment interval.

Clinical Results

FDA Approval

This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.The accelerated FDA approval of Darzalex was based on two studies.

Study 1:

This open-label trial evaluated Darzalex monotherapy in 106 patients with relapsed or refractory multiple myeloma who had received at least 3 prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent or who were double-refractory to a proteasome inhibitor and an immunomodulatory agent. Darzalex 16 mg/kg was administered with pre- and post-infusion medication. Treatment continued until unacceptable toxicity or disease progression. The overall response rate was 29.2%,  including a PI and an IMiD. Stringent complete response was reported in 2.8%f patients, very good partial response was reported in 9.4% of patients, and partial response was reported in 17% of patients. The median time to response was 1 month and the median duration of response was 7.4 months.

Study 2:

This open-label dose escalation trial evaluated Darzalex monotherapy in 42 patients with relapsed or refractory multiple myeloma who had received at least 2 different cytoreductive therapies. Darzalex 16 mg/kg was administered with pre- and post-infusion medication. Treatment continued until unacceptable toxicity or disease progression. Overall response rate was 36%, with 1 CR and 3 VGPR. The median time to response was 1 month. The median duration of response was not estimable (range: 2.2 to 13.1+ months).

Side Effects

Adverse effects associated with the use of Darzalex may include, but are not limited to, the following:

  • infusion reactions
  • fatigue
  • nausea
  • back pain
  • pyrexia
  • cough
  • upper respiratory tract infection

Mechanism of Action

CD38 is a transmembrane glycoprotein (48 kDa) expressed on the surface of hematopoietic cells, including multiple myeloma and other cell types and tissues and has multiple functions, such as receptor mediated adhesion, signaling, and modulation of cyclase and hydrolase activity. Daratumumab is an IgG1κ human monoclonal antibody (mAb) that binds to CD38 and inhibits the growth of CD38 expressing tumor cells by inducing apoptosis directly through Fc mediated cross linking as well as by immune-mediated tumor cell lysis through complement dependent cytotoxicity (CDC), antibody dependent cell mediated cytotoxicity (ADCC) and antibody dependent cellular phagocytosis (ADCP). Myeloid derived suppressor cells (MDSCs) and a subset of regulatory T cells (CD38+Tregs) express CD38 and are susceptible to daratumumab mediated cell lysis.

Additional Information

For additional information regarding Darzalex or multiple myeloma, please visit https://www.darzalex.com/