The U.S. Food and Drug Administration (FDA) has approved Darzalex (daratumumab) injection for intravenous infusion 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.
A reminder; multiple myeloma is an incurable blood cancer that occurs when malignant plasma cells grow uncontrollably in the bone marrow.
Janssen Biotech, Inc., a Janssen Pharmaceutical Company of Johnson & Johnson, on Tuesday in a press release announcing the approval, noted that multiple myeloma is the third most common blood cancer in the U.S., following only leukemia and lymphoma.
Janssen added that this indication was 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.
As for Darzalex, Janssen further says it is the first human anti-CD38 monoclonal antibody (mAb) approved anywhere in the world. CD38 is a surface protein that is expressed by most, if not all, multiple myeloma cells, Janssen says.
According to Johnson Johnson’s pharmaceutical company, Darzalex is believed to induce tumor cell death through multiple immune-mediated mechanisms of action, in addition to apoptosis, in which a series of molecular steps in a cell lead to its death.
Janssen points out that its approval comes just two months after the Biologics License Application (BLA) was accepted for Priority Review by the FDA in September 2015. Furthermore, Darzalex received Breakthrough Therapy Designation from the FDA for this indication in May 2013.
Promising new immunotherapy
Darzalex clinical trial investigator Paul G. Richardson, M.D., Clinical Program Leader and Director of Clinical Research, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute remarked that multiple myeloma is a highly complex disease and remains incurable, with almost all patients relapsing or becoming resistant to therapy.
Dr Richardson said: “With Darzalex, we have a promising new immunotherapy, which has shown pronounced efficacy as a single agent with an acceptable adverse event profile. This is especially important for treating these heavily pre-treated patients in whom all of the major classes of currently available medicines have failed.”
Sagar Lonial, M.D., Chief Medical Officer, Winship Cancer Institute of Emory University MMY2002 investigator said: “The responses we saw in clinical trials that led to today’s approval were striking, especially considering that these patients received a median of five prior lines of therapy.”
He noted that the mechanism of action for Darzalex might play an important role in its single-agent activity among this group of advanced-stage multiple myeloma patients.
“Living with multiple myeloma is challenging, both physically and emotionally, especially as the disease progresses and treatment options become more limited,” said Debby Graff, a patient enrolled in a clinical trial at Dana-Farber Cancer Institute. “I am encouraged by emerging treatments for multiple myeloma, and I have a new outlook on my path forward.”
Warnings and precautions for Darzalex
According to Janssen, the warnings and precautions for Darzalex include infusion reactions, interference with serological testing and interference with determination of complete response (see Important Safety Information). The most frequently reported adverse reactions (incidence ≥20%) were: fatigue, nausea, back pain, pyrexia, cough and upper respiratory tract infection, Janssen concluded.