FDA approves Janssen’s DARZALEX (daratumumab) to treat Multiple Myeloma

The Janssen Pharmaceutical Companies of Johnson & Johnson announced that the U.S. Food and Drug Administration (FDA) has approved DARZALEX (daratumumab) in combination with VELCADE (bortezomib), a proteasome inhibitor (PI); melphalan, an alkylating agent; and prednisone – VMP – for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT). DARZALEX is the first monoclonal antibody approved for newly diagnosed patients with this disease. Clinical trial results showed DARZALEX in combination with VMP reduced the risk of disease progression or death by 50 percent compared to treatment with VMP alone.

“This approval is significant as we now have the first antibody-based regimen for treating newly diagnosed multiple myeloma patients who are not eligible for a stem cell transplant,” said Andrzej Jakubowiak, M.D., Ph.D., Director of the Multiple Myeloma Program at University of Chicago Medical Center, Chicago, Illinois and a DARZALEX clinical study investigator. “In clinical studies, patients who received treatment with daratumumab experienced a lower risk of disease progression and higher rates of response.”

The FDA approval of DARZALEX in combination with VMP is supported by data from the randomized, open-label, multicenter Phase 3 ALCYONE (MMY3007) study, recently published in the New England Journal of Medicine. The combination of DARZALEX with VMP reduced the risk of disease progression or death by 50 percent, compared to treatment with VMP alone (Hazard Ratio [HR] = 0.50; 95 percent CI [0.38-0.65], p<0.0001). The median progression-free survival (PFS) for DARZALEX-VMP had not yet been reached, compared to a median PFS of 18.1 months for patients who received VMP alone.

“A patient’s best chance at lasting remission often begins with a durable response to frontline therapy, because multiple myeloma can become more difficult to treat after relapse,” said Maria-Victoria Mateos, M.D., Ph.D., Director of the Myeloma Unit at University Hospital of Salamanca-IBSAL, Salamanca, Spain and ALCYONE primary investigator. “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.”

Treatment with DARZALEX in combination with VMP significantly improved overall response rates (91 vs. 74 percent) compared to VMP alone. Additionally, measures of stringent complete response (18 vs. 7 percent), complete response or better (43 vs. 24 percent) and very good partial response or better (71 vs. 50 percent) all showed marked improvement. Patients receiving DARZALEX in combination with VMP achieved a more than three-fold increase in the minimal residual disease (MRD) negativity rate (22 vs. 6 percent) compared to those who received VMP alone.

In the ALYCONE study, the most frequent adverse reactions (>20 percent) with at least 5 percent greater frequency in the DARZALEX-VMP arm were upper respiratory tract infection (48 vs. 28 percent), infusion reactions (28 vs. 0 percent) and peripheral edema (21 vs. 14 percent).  Serious adverse reactions with at least a 2 percent greater incidence in the DARZALEX-VMP arm vs. VMP were pneumonia (11 vs. 4 percent), upper respiratory tract infection (5 vs.1 percent) and pulmonary edema (2 vs. 0 percent).  The most common Grade 3/4 treatment-emergent hematology laboratory abnormalities for DARZALEX-VMP vs. VMP were lymphopenia (58 vs. 53 percent), neutropenia (44 vs. 43 percent) and thrombocytopenia (38 vs. 42 percent). The warnings and precautions for DARZALEX include infusion reactions, interference with cross-matching and red blood cell antibody screening, neutropenia and thrombocytopenia (see Important Safety Information).

“Slowing the progression of myeloma translates to more time in remission for those battling the disease. This latest approval for DARZALEX in combination with VMP is an exciting step forward for newly diagnosed patients and the healthcare teams who treat them,” said Paul Giusti, President and CEO of the Multiple Myeloma Research Foundation (MMRF). “The MMRF congratulates Janssen, our long-time collaborator in myeloma research, the dedicated healthcare providers in the myeloma community as well as the patients who donate their time and data on clinical trials, for making this critical new combination therapy possible.”

Today’s FDA approval marks the fifth indication for DARZALEX, the first CD38-directed antibody approved anywhere in the world and the first antibody approved for newly diagnosed patients with multiple myeloma who are transplant ineligible. DARZALEX was first approved by the FDA in November 2015 as a monotherapy 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 an immunomodulatory agent. DARZALEX received additional approvals in November 2016 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. In June 2017, DARZALEX received approval in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a PI.

“We are grateful to the patients and physicians who participated in the clinical program that enabled today’s important approval of DARZALEX combination therapy as a treatment option for newly diagnosed patients with multiple myeloma who are transplant ineligible,” said Peter Lebowitz, M.D., Ph.D, Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC. “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.”

SOURCE: The Janssen Pharmaceutical Companies of Johnson & Johnson