Photo courtesy of Janssen
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for daratumumab (Darzalex), a CD38-directed monoclonal antibody (mAb), as part of combination therapy for patients with multiple myeloma (MM).
The designation is for daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone for the treatment of MM patients who have received at least 1 prior therapy.
This is the second breakthrough designation the FDA has granted to daratumumab.
The FDA’s breakthrough designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.
To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
In May 2013, the FDA granted daratumumab breakthrough designation for the treatment of MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.
In November 2015, daratumumab received accelerated approval from the FDA for this indication. Continued approval of the mAb may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Phase 3 trials
The newest breakthrough designation for daratumumab was based on data from two phase 3 studies—CASTOR (MMY3004) and POLLUX (MMY3003). Both studies were sponsored by Janssen Biotech, Inc., the company developing daratumumab.
In the CASTOR trial, researchers compared daratumumab-bortezomib-dexamethasone to bortezomib-dexamethasone in MM patients who had received at least 1 prior therapy.
The researchers said the addition of daratumumab significantly improved progression-free survival without increasing the cumulative toxicity or the toxicity of the bortezomib-dexamethasone combination.
Results from this trial were presented at the 2016 ASCO Annual Meeting.
In the POLLUX trial, researchers compared daratumumab-lenalidomide-dexamethasone to lenalidomide-dexamethasone in MM patients who had received at least 1 prior therapy.
According to the researchers, daratumumab-lenalidomide-dexamethasone conferred the highest response rate reported to date in the treatment of relapsed/refractory MM, significantly improved progression-free survival compared to lenalidomide-dexamethasone, and had a manageable safety profile.
These results were presented at the 21st Congress of the European Hematology Association.
