FDA Approves Darzalex Combo Therapy for Certain Newly Diagnosed Patients

The U.S. Food and Drug Administration (FDA) has approved Darzalex (daratumumab) in combination with standard therapy for the treatment of patients with newly-diagnosed multiple myeloma who are not eligible for stem cell transplants, according to Janssen Pharmaceuticals.

Darzalex, created by Genmab, and developed and commercialized by Janssen Pharmaceuticals, is the first human anti-CD38 monoclonal antibody approved anywhere in the world.

Darzalex is an antibody that targets and binds to a protein called CD38, which is present in high numbers on the surface of myeloma cells, regardless of the severity of the disease. It is believed to work by directly killing cancer cells, and/or triggering the person’s immune system to attack and destroy them.

The FDA’s approval is supported by results from the randomized, open-label, multicenter Phase 3 ALCYONE clinical trial (NCT02195479), which included 706 newly-diagnosed myeloma patients who were not suitable to receive autologous stem cell transplant.

Patients were randomized to receive standard therapy known as VMP – a combination of Velcade (bortezomib), Alkeran (melphalan), and prednisone – alone (356 patients), or in combination with Darzalex (350 patients). The treatment was given for nine cycles, after which patients continued receiving Darzalex as maintenance therapy for 28-day cycles until disease progression.

The addition of Darzalex to VMP combo reduced the risk of disease progression or death by half, compared to VMP alone. Progression-free survival (PFS) – the length of time a patient lives without disease progression – hadn’t been reached yet for patients in the Darzalez plus VMP group, while the VMP group had a median PFS of 18.1 months.

Response rates were significantly higher in the Darzalex group (90.9%) compared to patients receiving VMP alone (73.9%). Complete responses or better were achieved by almost twice as many patients receiving Darzalex (42.6%) than those on the VMP group (24.4%).

Also, significantly more patients in the Darzalex group (22.3%) were negative for minimal residual disease – cancer cells lingering in the body after treatment that often lead to relapse – compared to those who received VMP alone (6.2%).

“Combination therapy with daratumumab resulted in deep and durable responses in newly diagnosed patients with multiple myeloma who are transplant ineligible, supporting this regimen as an important new treatment option for these patients,” Maria-Victoria Mateos, MD, PhD, ALCYONE’s primary investigator, said in a press release.

The most frequently reported adverse events associated with Darzalex therapy were upper respiratory tract infection (48%), infusion-related reactions (28%), and swelling of the limbs (21%).

Among severe or very severe adverse events, infection events were increased in the Darzalex group, whereas blood-related events – although frequent – were reported at similar rates by both treatment groups.

A similar application to the European Medicines Agency (EMA) to broaden the existing marketing authorization for Darzalex in the European Union is pending.

Darzalex was first approved for multiple myeloma in November 2015 as a single therapy for patients who had received at least three previous lines of treatment. Additional approvals were granted in November 2016 and June 2017 for Darzalex as an add-on therapy to different treatment regimens.

“Darzalex has redefined how we approach the treatment of multiple myeloma, and we continue to evaluate its potential in combination with other regimens, with the aim of arresting the disease at its earliest stages,” added Peter Lebowitz, MD, PhD, head of Global Oncology Therapeutic Area at Janssen.