The Food and Drug Administration has granted accelerated approval for Darzalex (daratumumab) for the treatment of patients with multiple myeloma who have received at least three prior treatments, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.
Darzalex injection, a monoclonal antibody that works by helping certain cells in the immune system attack cancer cells, is the first monoclonal antibody approved for the treatment of myeloma.
"Targeting proteins that are found on the surface of cancer cells has led to the development of important oncology treatments," Richard Pazdur, MD, Director of the FDA's Office of Hematology and Oncology Products, said in a statement. "Darzalex provides another treatment option for patients with multiple myeloma who have become resistant to other therapies."
Accelerated Approval & Other Designations
The accelerated approval program, under which Darzalex was approved, allows the FDA to approve a drug to treat a serious disease based on clinical data showing that the drug has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients.
Darzalex, marketed by Janssen Biotech, has also been granted Breakthrough Therapy, Priority Review, and Orphan Drug designations. Breakthrough Therapy status is granted for a drug that is intended to treat a serious condition when, at the time an application is submitted, preliminary clinical evidence indicates that a drug may demonstrate substantial improvement over available therapies.
Priority Review designation is granted to drug applications that show a significant improvement in safety or effectiveness in the treatment of a serious condition. Orphan Drug status provides incentives such as tax credits, user fee waivers, and eligibility for market exclusivity to assist and encourage the development of drugs for rare diseases.
Safety & Efficacy
Darzalex's safety and efficacy were demonstrated in two open-label studies. In the Phase II MMY2002 (SIRUS) study of 106 patients with multiple myeloma who had received a median of five lines of prior therapy, including a proteasome inhibitor and an immunomodulatory agent, all received Darzalex and 31 patients had a complete or partial reduction in their tumor burden. The response lasted an average of 7.4 months. In the other study, 42 patients received Darzalex and 15 had a complete or partial reduction in their tumor burden.
"The responses we saw in clinical trials that led to the approval were striking, especially considering that these patients received a median of five prior lines of therapy," said MMY2002 investigator Sagar Lonial, MD, Chief Medical Officer at Winship Cancer Institute of Emory University and Professor and Executive Vice Chair in the Department of Hematology and Medical Oncology at Emory University School of Medicine.
The most common side effects for Darzalex were infusion-related reactions, fatigue, nausea, back pain, fever, and cough. The drug may also cause lymphopenia, neutropenia, leukopenia, anemia, and thrombocytopenia; severe infusion reactions reported with treatment with Darzalex included bronchospasm, dyspnea, hypoxia, and hypertension.
A statement from the FDA notes that blood banks should be informed when patients are receiving Darzalex, because the drug may interfere with certain tests that are done by blood banks (such as antibody screening) for patients who need a blood transfusion. Women who are pregnant should not use Darzalex, and women planning to become pregnant should use effective contraceptives during and for at least three months after treatment.
Clinical Quick Facts: Darzalex
Drug: Darzalex (daratumumab)
Approved Indication: Treatment of patients with multiple myeloma who have received at least three prior treatments, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent
Serious Side Effects: Lymphopenia, neutropenia, leukopenia, anemia, thrombocytopenia, and severe infusion reactions, including bronchospasm, dyspnea, hypoxia, and hypertension
Common Side Effects: Infusion-related reactions, fatigue, nausea, back pain, fever, and cough