Janssen Biotech announces US FDA approval of DARZALEX

Janssen Biotech, Inc. announced that the U.S. FDA has approved the immunotherapy DARZALEX® (daratumumab) in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies including lenalidomide (an immunomodulatory agent) and a proteasome inhibitor (PI). Clinical trial results showed an overall response rate (ORR) of 59.2 percent with DARZALEX in combination with pomalidomide and dexamethasone in these patients.

DARZALEX is the first CD38-directed 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 an immunomodulatory agent. It 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.⁴ To date, approximately 16,000 patients have been treated with DARZALEX.

“Despite tremendous progress, most patients with multiple myeloma continually relapse or become resistant to available therapies, such as PIs and immunomodulatory agents. Therefore, these patients continue to need new options,” said Ajai Chari M.D., Associate Professor of Medicine, Multiple Myeloma Program and Associate Director of Clinical Research, Mount Sinai Hospital. “With today’s approval of DARZALEX, we now have a promising new combination therapy that in clinical trials demonstrated pronounced clinical benefit for patients who have relapsed on two of the most widely used treatments.”

This new indication for DARZALEX is supported by data from the Phase 1b EQUULEUS study, which showed that the combination of DARZALEX with pomalidomide and dexamethasone resulted in an ORR of 59.2 percent (95 percent CI: 49.1, 68.8), with very good partial response (VGPR) achieved in 28.2 percent of patients. Complete response (CR) was achieved in 5.8 percent of patients, stringent CR (sCR) was achieved in 7.8 percent of patients, and partial response (PR) was achieved in 17.5 percent of patients.1 The median time to response was one month (range: 0.9 to 2.8 months), and the median duration of response was 13.6 months (range: 0.9+ to 14.6+ months).1

“The recent approval of DARZALEX is significant for patients and clinicians who urgently need new options and regimens. This milestone underscores the versatility of DARZALEX with a range of treatment regimens,” said Peter F. Lebowitz, M.D., Ph.D., Global Oncology Head, Janssen Research & Development, LLC. “We look forward to continued study of daratumumab in earlier stages of multiple myeloma and other cancers.”

Overall, the safety of the DARZALEX combination therapy was consistent with the known safety profiles of DARZALEX monotherapy and pomalidomide plus dexamethasone, respectively. Warnings and precautions in the Prescribing Information include: infusion reactions, interference with cross-matching and red blood cell antibody screening, neutropenia and thrombocytopenia.1 In the EQUULEUS trial, the most frequent (>20 percent) adverse reactions (ARs) were infusion reactions (50 percent), diarrhea (38 percent), constipation (33 percent), nausea (30 percent), vomiting (21 percent), fatigue (50 percent), pyrexia (25 percent), upper respiratory tract infection (50 percent), muscle spasms (26 percent), back pain (25 percent), arthralgia (22 percent), dizziness (21 percent), insomnia (23 percent), cough (43 percent) and dyspnea (33 percent).1 The overall incidence of serious ARs was 49 percent.1 Serious ARs (Grade 3/4) reported in =5 percent of patients included pneumonia (7 percent).1 Thirteen percent of patients discontinued therapy due to an AR.1 The most common treatment-emergent hematology laboratory abnormalities were neutropenia (95 percent), lymphopenia (94 percent), thrombocytopenia (75 percent) and anemia (57 percent).1 The most common Grade 3 treatment-emergent hematology laboratory abnormalities were lymphopenia (45 percent), neutropenia (36 percent), anemia (30 percent) and thrombocytopenia (10 percent).1 The most common Grade 4 treatment-emergent hematology laboratory abnormalities were neutropenia (46 percent), lymphopenia (26 percent) and thrombocytopenia (10 percent).

The Phase 1b EQUULEUS study included 103 patients with multiple myeloma who had received a prior PI and an immunomodulatory agent.1 Patients received 16 mg/kg of DARZALEX in combination with pomalidomide and low-dose dexamethasone until disease progression.1 The median patient age was 64 years, with 8 percent of patients aged 75 or older.1 Patients in the study had received a median of four prior lines of therapy, and 74 percent of patients had received prior autologous stem cell transplant (ASCT).1 Ninety-eight percent of patients received prior bortezomib treatment and 33 percent of patients received prior carfilzomib treatment. All patients received prior lenalidomide treatment, with 98 percent of patients previously treated with the combination of bortezomib and lenalidomide.1 Eighty nine percent of patients were refractory to lenalidomide, 71 percent were refractory to bortezomib, and 64 percent of patients were refractory to bortezomib and lenalidomide.

The recommended dose of DARZALEX is 16 mg/kg body weight administered as an intravenous infusion.1 The dosing schedule for DARZALEX in combination with pomalidomide and dexamethasone begins with weekly administration (weeks 1-8) and reduces in frequency over time to every two weeks (weeks 9-24) and ultimately every four weeks (week 25 onwards until disease progression).1

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.6 DARZALEX is commercialized in the U.S. by Janssen Biotech, Inc. For full Prescribing Information, please visit www.DARZALEX.com.

DARZALEX® (daratumumab) injection for intravenous use is the first CD38-directed antibody approved anywhere in the world.2 CD38 is a surface protein that is highly expressed across multiple myeloma cells, regardless of disease stage.7 DARZALEX is believed to induce tumor cell death through multiple immune-mediated mechanisms of action, including complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), as well as through apoptosis, in which a series of molecular steps in a cell lead to its death.1 A subset of myeloid derived suppressor cells (MDSCs), CD38+ regulatory T cells (Tregs) and CD38+ B cells (Bregs) were decreased by DARZALEX.1 DARZALEX is being evaluated in a comprehensive clinical development program that includes five Phase 3 studies across a range of treatment settings in multiple myeloma, such as in frontline and relapsed settings.8,9,10,11,12 Additional studies are ongoing or planned to assess its potential for a solid tumor indication and in other malignant and pre-malignant diseases in which CD38 is expressed, such as smoldering myeloma.13,14,15 DARZALEX was the first CD38-directed antibody to receive regulatory approval to treat relapsed or refractory multiple myeloma.³

Multiple myeloma is an incurable blood cancer that occurs when malignant plasma cells grow uncontrollably in the bone marrow.16,17 Refractory cancer occurs when a patient's disease is resistant to treatment or in the case of multiple myeloma, patients progress within 60 days of their last therapy.18,19 Relapsed cancer means the disease has returned after a period of initial, partial or complete remission.20 Globally, it is estimated that 124,225 people were diagnosed and 87,084 died from the disease in 2015.21,22 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms, which can include bone fracture or pain, low red blood counts, fatigue, calcium elevation, kidney problems or infections.23

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