Darzalex Secures Breakthrough Therapy Designation

July 26, 2016

The mAb, in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, was granted a Breakthrough Therapy Designation from FDA for the treatment of multiple myeloma.

On July 26, 2016 FDA granted Breakthrough Therapy Designation to Genmab and Janssen’s multiple myeloma monoclonal antibody (mAb) treatment Darzalex (daratumumab) in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for patients that have received at least one prior therapy. Darzalex was originally approved in November 2015, and was the first mAb approved to treat multiple myeloma.

Results from Phase III trials show that daratumumab in combination bortezomib and dexamethasone reduced disease progression by 61% in patients with multiple myeloma. During Phase III CASTOR trials, the three-drug combination increased overall response rate from 63% to 83%. In an American Society of Clinical Oncology abstract, researchers reviewing the CASTOR study noted that the combination of daratumumab, bortezomib, and dexamethasone should be considered the new standard of care for patients with relapsed refractory multiple myeloma.

While daratumumab has shown to improve treatment for patients with multiple myeloma, some scientists think daratumumab, which works by binding to the CD38 molecule, could have implications for patients requiring blood transfusions. In a letter to the editor published on July 21, 2016 in the New England Journal of Medicine Michael F. Murphy, MD, of the John Radcliffe Hospital, and colleagues raised concerns about the drug’s interference with blood compatibility testing for patients requiring transfusion.

According to the American Association of Blood Banks (AABB), anti-CD38 treatments like daratumumab can cause positive reactions in indirect antiglobulin tests, antibody detection tests, antibody identification panels, and antihuman globulin crossmatches. This often leads to delays in issuing red blood cell units to patients, the AABB says. Murphy and colleagues commented that during Phase I and II trials, daratumumab in patient’s plasma caused false positive antibody screens. After further examination, researchers were able to discover effective methods to circumvent this interference. However, Murphy continues, many of these methods are not readily available to hospitals completing compatibility testing.

Source: Genmab, FDA, NEJM, AABB