Janssen-Cilag International NV has today announced that the European Commission (EC) has granted conditional approval to DARZALEX® (daratumumab) for monotherapy of adult patients with relapsed and refractory multiple myeloma (MM), whose prior therapy included a proteasome inhibitor (PI) and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. Daratumumab was approved under an accelerated assessment, a process reserved for medicinal products expected to be of major public health interest, particularly from the point of view of therapeutic innovation.1
Daratumumab is the first CD38-directed monoclonal antibody (mAb) approved in Europe. It works by binding to CD38, a signaling molecule highly expressed on the surface of multiple myeloma cells regardless of stage of disease.2-4 In doing so, daratumumab triggers the patient’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death via apoptosis (programmed cell death).
“Despite recent advances, multiple myeloma remains a complex, incurable disease, with relapse being inevitable in almost all patients. With each relapse, the disease typically becomes more aggressive and more challenging to treat,” said Professor Jesús San Miguel, Director of Clinical & Translational Medicine, Universidad de Navarra, Spain. “Daratumumab has shown promising efficacy results and a manageable safety profile as a single agent for heavily pre-treated and refractory myeloma patients. Overall survival improved significantly in these patients, whose prognosis is typically very poor, and who therefore have the greatest need for new treatments.”
The approval of daratumumab was based on data from the Phase 2 MMY2002 (SIRIUS) study, published in The Lancet; the Phase 1/2 GEN501 study, published in The New England Journal of Medicine; and data from three additional supportive studies. Findings from a combined efficacy analysis of the GEN501 and MMY2002 (SIRIUS) trials demonstrated that after a mean follow-up of 14.8 months, the estimated median OS for single-agent daratumumab (16 mg/kg) in these heavily pre-treated patients was 20 months (95 percent CI, 15-not estimable). The overall response rate (ORR) for the combined analysis was 31 percent, and 83 percent of patients achieved stable disease or better. Daratumumab demonstrated a tolerable and clinically manageable safety profile as a monotherapy in heavily pre-treated patients. The most common adverse events (AEs) in the Phase 2 MMY2002 (SIRIUS) trial, which occurred in more than 20 percent of patients, were fatigue, anemia, nausea, thrombocytopenia, back pain, neutropenia and cough. The most common adverse events (AEs) in the Phase 1/2 GEN501 trial were fatigue, allergic rhinitis, and pyrexia (fever).
“Today’s decision on daratumumab is fantastic news for patients as it will help to address a major area of unmet need in people with relapsed or refractory myeloma,” said Sarper Diler, MD, PhD, President of Myeloma Patients Europe. “However, there is still a lot of work to be done to ensure that daratumumab is available for patients in health systems across Europe.”
“The approval of daratumumab within an accelerated timeframe is a result of working with patient-focused urgency, delivering against unmet needs with transformational science and through strong collaborations,” said Jane Griffiths, Company Group Chairman, Janssen Europe, Middle East and Africa. “We are delighted that daratumumab has been approved in Europe and will continue to study its potential across the treatment continuum in multiple myeloma and other tumor types.”
The marketing authorization approval follows a positive opinion from the European Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued on 01 April 2016. This approval allows for the marketing of daratumumab in all 28 member states and the three European Economic Area countries of the European Union.
Janssen has exclusive worldwide rights to the development, manufacturing and commercialization of daratumumab. Janssen licensed daratumumab from Genmab A/S in August 2012.