On 16 November, 2015 the US Food and Drug Administration (FDA) granted accelerated approval for daratumumab (Darzalex) to treat 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. It is the first monoclonal antibody approved for the treatment of multiple myeloma.
Darzalex is given as an infusion. It is a human IgG1k monoclonal antibody that binds with high affinity to the transmembrane ectoenzyme, CD38, on the surface of multiple myeloma cells. It has multiple mechanisms of action, including complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, antibody-dependent cellular phagocytosis, apoptosis and modulation of CD38 enzymatic activity.
“Targeting proteins that are found on the surface of cancer cells has led to the development of important oncology treatments,” said Dr Richard Pazdur, director of the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research. “Darzalex provides another treatment option for patients with multiple myeloma who have become resistant to other therapies.”
The safety and efficacy of Darzalex were demonstrated in two open-label studies. In one study of 106 participants receiving Darzalex, 29% of patients experienced a complete or partial reduction in their tumour burden, which lasted for an average of 7.4 months. In the second study of 42 participants receiving Darzalex, 36% had a complete or partial reduction in their tumour burden.
The most common side effects of Darzalex were infusion-related reactions, fatigue, nausea, back pain, fever and cough.
Darzalex may also result in lymphopenia, neutropenia, and leukopenia or anemia and thrombocytopenia. Blood banks should be informed that 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.
The FDA granted breakthrough designation for this application based on preliminary clinical evidence suggesting that if approved, Darzalex may offer a substantial improvement over available therapies. Darzalex also received priority review and orphan drug designations. Priority review status is granted to applications for drugs that, if approved, would be a significant improvement in safety or effectiveness in the treatment of a serious condition. Orphan drug designation provides incentives such as tax credits, user fee waivers and eligibility for orphan drug exclusivity to assist and encourage the development of drugs for rare diseases.
Darzalex was approved under the agency’s accelerated approval programme, which allows the approval of a drug to treat a serious or life-threatening disease based on clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients. This programme provides earlier patient access to promising new drugs while the company conducts confirmatory clinical trials.
Darzalex is marketed by Janssen Biotech of Horsham, Pennsylvania.