Janssen Biotech announced the U.S. Food and Drug Administration (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 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 approved CD38-directed antibody. 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. 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," Ajai Chari M.D., Associate Professor of Medicine, Multiple Myeloma Program and Associate Director of Clinical Research, Mount Sinai Hospital said. "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. 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).
Overall, the safety of the Darzalex combination therapy was consistent with the known safety profiles of Darzalex monotherapy and pomalidomide plus dexamethasone, respectively.
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. The median patient age was 64 years with 8 percent of patients aged 75 or older. 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). 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. 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. 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).