FDA Approves Darzalex With Two Standard-of-Care Regimens for Treatment of Multiple Myeloma

Approval supported by phase 3 survival data

The FDA has given the green light to daratumumab (Darzalex, Janssen Biotech) 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. The approval comes three months after a supplemental biologics license application was submitted to the FDA in August 2016. Daratumumab received a breakthrough therapy designation for this indication in July 2015.

Clinical studies have shown that daratumumab, in combination with lenalidomide (an immunomodulatory agent) and dexamethasone, reduced the risk of disease progression or death by 63% compared with lenalidomide and dexamethasone alone in patients with multiple myeloma who received a median of one prior therapy (hazard ratio [HR], 0.37; P < 0.0001). In combination with bortezomib (a proteasome inhibitor) and dexamethasone, daratumumab reduced the risk of disease progression or death by 61% compared with bortezomib and dexamethasone alone in patients with multiple myeloma who received a median of two prior lines of therapy (HR, 0.39; P < 0.0001). 

Daratumumab injection for intravenous use is the first CD38-directed cytolytic antibody approved anywhere in the world, according to Janssen. CD38 is a surface protein that is highly expressed in multiple myeloma cells regardless of disease stage. Daratumumab is believed to induce tumor cell death through multiple immune-mediated mechanisms of action, including complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and antibody-dependent cellular phagocytosis, as well as through apoptosis. A subset of myeloid-derived suppressor cells, CD38-positive regulatory T cells (Tregs), and CD38-positive B cells (Bregs) were reduced by daratumumab.

The new approval was supported by data from two phase 3 studies.

In the open-label POLLUX trial, median progression-free survival (PFS) in the daratumumab arm has not been reached, compared with median PFS of 18.4 months for patients who received lenalidomide and dexamethasone alone, with a median follow-up of 13.5 months. In addition to meeting the primary endpoint of improved PFS, daratumumab significantly increased the overall response rate (ORR) compared with lenalidomide and dexamethasone alone (91% vs. 75%, respectively; P < 0.0001), including doubling the complete response (CR) rate (25% vs. 12%; P < 0.0001) and significantly increasing the very good partial response (VGPR) rate (32% vs. 24%; P < 0.0001). These results were published in the New England Journal of Medicine in October 2016.

In the open-label CASTOR trial, median PFS in the daratumumab arm has not been reached compared with median PFS of 7.2 months for patients who received bortezomib and dexamethasone alone, with a median follow-up of 7.4 months. In addition to meeting the primary endpoint of improved PFS, daratumumab also significantly increased the ORR compared with bortezomib and dexamethasone alone (79% vs. 60%, respectively; P < 0.0001), including doubling the CR rate (14% vs. 7%; P < 0.0001) as well as the VGPR rate (38% vs. 19%; P < 0.0001). These results were published in New England Journal of Medicine in August 2016.

Source: PR Newswire; November 21, 2016.