Genmab Announces U.S. FDA Approval of DARZALEX™ (daratumumab) for Multiple Myeloma and Updates Financial Guidance
Company Announcement
• DARZALEX (daratumumab) approved by U.S. FDA for heavily pre-treated or double refractory multiple myeloma
• First monoclonal antibody approved for multiple myeloma
• Financial guidance updated to include USD 45 million milestone payment
Copenhagen, Denmark; November 16, 2015 — Genmab A/S (OMX: GEN) announced today the U.S. Food and Drug Administration (FDA) has approved DARZALEX™ (daratumumab) injection for intravenous infusion for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD), or who are double-refractory to a PI and IMiD.1 This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
DARZALEX is the first human CD38 monoclonal antibody (mAb) approved anywhere in the world and the first therapeutic antibody ever approved to treat multiple myeloma. The approval comes just two months after the Biologics License Application (BLA) was accepted for Priority Review by the FDA in September 2015. In May 2013, DARZALEX received Breakthrough Therapy Designation from the FDA for the indication approved today. In August 2012, Genmab granted Janssen Biotech, Inc. an exclusive worldwide license to develop, manufacture and commercialize DARZALEX.
Genmab will receive a milestone payment from Janssen of USD 45 million associated with the first commercial sale of the product in the United States. As this is expected to occur quickly after this approval, Genmab is improving its financial guidance for the year. See the Outlook section of this announcement for more information.
"This is an important day for patients in the United States with double refractory multiple myeloma, who will now have DARZALEX as a new treatment option for this incurable disease. The successful approval of DARZALEX is the culmination of many years of hard work, perseverance and collaboration on the part of clinical study investigators, Genmab employees and our colleagues at Janssen. Our work at Genmab is aimed at improving the lives of patients and we are both proud and humbled to have created this first-in-class therapeutic antibody and to have played a key part in the rapid and expansive development of DARZALEX," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.
The pivotal Phase II MMY2002 (SIRIUS) study showed treatment with single-agent DARZALEX resulted in an overall response rate (ORR) of 29.2 percent in patients who received a median of five prior lines of therapy, including a PI and an IMiD, and is expected to be published in a top medical journal soon. Stringent complete response (sCR) was reported in 2.8 percent of patients, very good partial response (VGPR) was reported in 9.4 percent of patients, and partial response (PR) was reported in 17 percent of patients. For responders, the median duration of response was 7.4 months. At baseline, 97 percent of patients were refractory to their last line of therapy, 95 percent were refractory to both a PI and an IMiD, and 77 percent were refractory to alkylating agents. Sixty-three percent were refractory to pomalidomide, and 50 percent were refractory to carfilzomib.1 Additional data from four other studies, including the Phase I/II GEN501 monotherapy study — published in The New England Journal of Medicine in August 2015 — also support this approval.
The warnings and precautions for DARZALEX include infusion-related reactions (IRRs) and interference with serological testing.2 The most commonly occurring adverse reactions (in 20 percent or more of patients in three pooled clinical studies) were IRRs, fatigue, nausea, back pain, anemia, neutropenia (abnormally low levels of neutrophils, a type of white blood cell) and thrombocytopenia (abnormally low levels of platelets in the blood).1
In data from three pooled clinical studies including a total of 156 patients, four percent of patients discontinued treatment due to adverse reactions, none of which were considered drug-related. IRRs were reported in approximately half of all patients treated with DARZALEX, the majority of which (91 percent) occurred during the first infusion. Seven percent of patients had an IRR at more than one infusion. Common (=5 percent) symptoms of IRRs included nasal congestion, chills, cough, allergic rhinitis, throat irritation, dyspnea, and nausea, and these were mild to moderate in severity.1 Severe IRRs (4 percent), including bronchospasm (1.3 percent), hypertension (1.3 percent), and hypoxia, or decreased oxygen supply to the tissues (0.6 percent), were also reported.1
The recommended dose of DARZALEX is 16 mg/kg body weight administered as an intravenous infusion.1 The dosing schedule begins with weekly administration (weeks 1 to 8), and reduces in frequency to every two weeks (weeks 9-24) and ultimately every four weeks (week 25 onwards until disease progression).1
Janssen is currently the global sponsor of all but one clinical study, the Phase I/II GEN501 monotherapy study which was conducted by Genmab. DARZALEX will be commercialized in the U.S. by Janssen Biotech, Inc.