Janssen Biotech, Inc. announced that the company has submitted a supplemental Biologics License Application (sBLA) for daratumumab (Darzalex) to the US Food and Drug Administration (FDA). The application seeks to expand the current indication, using daratumumab in combination with lenalidomide (an immunomodulatory agent) and dexamethasone, or bortezomib (a proteasome inhibitor [PI]) and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy.

Daratumumab received Breakthrough Therapy Designation from the FDA for this pending indication on July 25, 2016.

“Daratumumab has been shown to provide clinically meaningful benefit as a backbone therapy in combination with two of the most widely used treatment regimens for multiple myeloma,” said Peter F. Lebowitz, M.D., Ph.D., global oncology head, Janssen Research & Development, LLC. “Today’s submission marks an important step forward in realizing the full potential of daratumumab earlier in the treatment pathway, and we look forward to working with the FDA during its review of our application.”

Janssen has also submitted a request for Priority Review of this sBLA. The FDA will inform Janssen whether a Priority Review has been granted within the next 60 days. If the FDA grants Priority Review, the review should be completed within six months.

In November 2015, Darzalex was approved as a monotherapy by the FDA for the treatment of 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. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.1  Darzalex received Breakthrough Therapy Designation from the FDA for this indication in May 2013.

In May 2016, the European Commission (EC) granted conditional approval to  Darzalex monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy.

Darzalex (daratumumab) injection for intravenous use is the first CD38-directed monoclonal antibody (mAb) approved anywhere in the world. CD38 is a surface protein that is highly expressed across 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 (CDC), antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), as well as through apoptosis, in which a series of molecular steps in a cell lead to its death. Daratumumab also demonstrates other effects on the immune system, including lysis of immunosuppressive CD38+ regulatory T cells (Tregs) and myeloid derived suppressor cells (MDSCs).  Darzalex is being evaluated in a comprehensive clinical development programme that includes five phase 3 studies across a range of treatment settings in multiple myeloma, such as in frontline and relapsed settings. Additional studies are ongoing or planned to assess its potential for a solid tumor indication and in other malignant and pre-malignant diseases in which CD38 is expressed, such as smoldering myeloma and non-Hodgkin's lymphoma.  Darzalex was the first mAb to receive regulatory approval to treat relapsed or refractory multiple myeloma.

In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agree ment, which granted Janssen an exclusive license to develop, manufacture and commercialize  Darzalex.  Darzalex is commercialized in the US by Janssen Biotech, Inc.