FDA Breakthrough Designation to Janssen’s “Backbone Therapy” for Multiple Myeloma


Johnson and Johnson subsidiary Janssen Pharmaceuticals’ immunotherapy Darzalex® (daratumumab) received a Breakthrough Therapy Designation from U.S. Food and Drug Administration (FDA) in combination with the standard regimens lenalidomide/dexamethasone or bortezomib/dexamethasone for the treatment of multiple myeloma patients who had received at least one prior therapy.

janssen biotech logoThis is the second Breakthrough Therapy Designation for daratumumab. It received the first one in 2013. Daratumumab is an experimental human CD38 monoclonal antibody discovered by Danish company, Genmab and later Janssen received worldwide license to develop and commercialize it.


Figure 1. Janssen Pharmaceuticals’ Darzalex packaging (photo credit:

Darzalex is the first CD38-directed monoclonal antibody (mAb) intravenous injection approved in the world. It was also the first mAb to receive regulatory approval to treat relapsed or refractory multiple myeloma. CD38 is a surface protein overexpressed in multiple myeloma cells irrespective of the stage of the disease. It is proposed that daratumumab induce tumor cell death through multiple immune-mediated mechanisms of action.

daratumumab mechanism of action

Figure 2. Mechanism of action of daratumumab (photo credit: Immunol Rev. 2016 Mar;270(1):95-112. doi: 10.1111/imr.12389).

In 2015, FDA approved Darzalex for the treatment of multiple myeloma patients who had received at least three prior therapies including a proteasome inhibitor (PI) like bortezomib and an immunomodulatory agent like lenalidomide or the patients who are double refractory to a PI and an immunomodulatory agent.

In May 2016, Darzalex was granted conditional approval by the European Commission (EC) to treat adult patients with relapsed and refractory multiple myeloma who had received prior therapy including a PI and an immunomodulatory agent.

The two Phase III clinical study data supported daratumumab to procure the Breakthrough designation from FDA. The study was done in multiple myeloma patients who had received at least one prior therapy.

The clinical trial CASTOR compared the combination therapy of daratumumab with bortezomib/dexamethasone to daratumumab with bortezomib and dexamethasone individually. The result demonstrated reduced risk of disease progression and death in patients receiving the daratumumab with bortezomib/dexamethasone.

The clinical trial POLLUX evaluated the combined effect of daratumumab with lenalidomide/dexamethasone and of daratumumab with lenalidomide and dexamethasone individually. The results were favourable for daratumumab with lenalidomide/dexamethasone.

In 2015, approximately 124,225 patients were diagnosed and 87,084 died from multiple myeloma. It is a complex and difficult-to-treat disease with the higher chance of patients relapsing or becoming resistant to therapy.  It is designated as an orphan disease in US and Europe.

The patients who relapse after the treatment with the standard regimen (including PIs or immunomodulatory agents) have few options left for the treatment. In such situation, the breakthrough designation fuels up the development of the potential treatment which could support the existing standard treatment for multiple myeloma patients.

We are pleased that the FDA has granted a second Breakthrough Therapy Designation to daratumumab. This is an important recognition of the transformative potential of daratumumab and its possible benefit as a backbone therapy in combination with two of the most widely used regimens for multiple myeloma,” said Craig L. Tendler, M.D., Vice President, Late-Stage Development and Global Medical Affairs for Oncology, Hematology and Supportive Care, Janssen Research & Development, LLC. “We look forward to working closely with the FDA throughout the review process and remain committed to exploring the full clinical benefit of this promising compound for multiple myeloma patients who are eagerly awaiting new treatment options“.

Featured Image Credit:

Leave a reply

Your email address will not be published. Required fields are marked *