Janssen Biotech, Inc. announced the US Food and Drug Administration (FDA) has approved Darzalex (daratumumab) in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy.

Clinical studies have shown that Darzalex, in combination with lenalidomide (an immunomodulatory agent) and dexamethasone, reduced the risk of disease progression or death by 63 per cent, compared to lenalidomide and dexamethasone alone, in patients with multiple myeloma who received a median of one prior therapy (Hazard Ratio [HR]=0.37; 95 per cent CI [0.27, 0.52], p<0.0001). In combination with bortezomib (a proteasome inhibitor [PI]) and dexamethasone, Darzalex reduced the risk of disease progression or death by 61 per cent, compared to bortezomib and dexamethasone alone, in patients with multiple myeloma who received a median of two prior lines of therapy (HR=0.39; 95 percent CI [0.28, 0.53], p<0.0001).  Multiple myeloma is an incurable blood cancer that occurs when malignant plasma cells grow uncontrollably in the bone marrow.

The approval comes three months after a supplemental Biologics License Application (sBLA) was submitted to the FDA in August 2016. Darzalex received Breakthrough Therapy Designation from the FDA for this indication in July 2016.

“While tremendous progress in the treatment of multiple myeloma has been made in the past decade, patients and their physicians continue to need new treatment options,” said Meletios A. Dimopoulos,M.D., Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Alexandra General Hospital, Athens, Greece, a Darzalex clinical trial investigator. “With Darzalex, we have a potential new backbone therapy, which has shown pronounced efficacy as either a single agent or in combination with standard of care regimens. The addition of Darzalex also significantly improved progression-free survival in combination with two of the most widely used treatment classes, making it a versatile option for patients who have received at least one prior therapy.”

Darzalex is the first CD38-directed cytolytic antibody approved anywhere in the world. It was first approved by the FDA in November 2015 as a monotherapy treatment for patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double refractory to a PI and immunomodulatory agent.

Today’s approval is supported by data from two Phase 3 studies:

According to results from the open-label POLLUX (MMY3003) clinical study, the median progression-free survival (PFS) in the Darzalex arm has not been reached, compared with a median PFS of 18.4 months for patients who received lenalidomide and dexamethasone alone, with a median follow-up of 13.5 months. In addition to meeting the primary endpoint of improved PFS, Darzalex significantly increased the overall response rate (ORR) [91 per cent vs. 75 per cent, p<0.0001], compared to lenalidomide and dexamethasone alone, including doubling rates of complete response (CR) [25 percent vs. 12 per cent, p<0.0001] and significantly increasing very good partial response (VGPR) [32 percent vs. 24 percent, p<0.0001]. These results were published in The New England Journal of Medicine, with an accompanying editorial, in October 2016.7

According to results from the open-label CASTOR (MMY3004) clinical study, the median PFS in the Darzalex arm has not been reached, compared with a median PFS of 7.2 months for patients who received bortezomib and dexamethasone alone, with a median follow-up of 7.4 months. In addition to meeting the primary endpoint of improved PFS, Darzalex also significantly increased ORR [79 per cent vs. 60 per cent, p<0.0001], compared to bortezomib and dexamethasone alone, including doubling rates of CR [14 per cent vs. 7 per cent, p<0.0001] and significantly increasing VGPR [38 per cent vs. 19 per cent, p<0.0001]. These results were published in The New England Journal of Medicine in August 2016.

Updated results from these clinical studies will be presented as oral presentations at the 58th American Society of Hematology (ASH) Annual Meeting to be held in San Diego, CA from December 3-6, 2016 (Abstract #1150; Abstract #1151).

“The approval of daratumumab provides multiple myeloma patients with another versatile treatment option to help address their urgent medical needs,” said Paul Giusti, president and chief executive officer of theMultiple Myeloma Research Foundation (MMRF). “At the MMRF, we are excited by the groundbreaking work being done to bring effective, new treatments to patients.”

“We are proud of the rapid development and approval of Darzalex for use earlier in the treatment pathway, but our work does not stop here,” said Peter F. Lebowitz, M.D., Ph.D., global oncology head, Janssen Research & Development, LLC. “We are only starting to uncover the full potential of this compound, and we remain committed to the continued study of daratumumab to more fully understand its utility for patients with multiple myeloma and other cancer types.”


In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize Darzalex. Darzalex is commercialized in the US by Janssen Biotech, Inc.