FDA: Darzalex granted Breakthrough Therapy Designation for use in combination with standard of care regimens for patients with multiple myeloma
The FDA ( Food and Drug Administration ) has granted a Breakthrough Therapy Designation to the immunotherapy Darzalex ( Daratumumab ) in combination with Lenalidomide ( Revlimid ), an immunomodulatory agent, and Dexamethasone, or Bortezomib ( Velcade ), a proteasome inhibitor, and Dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy.
This marks the second time Darzalex has received a Breakthrough Therapy Designation, which is intended to expedite the development and review timelines of potential new medicines to treat serious or life-threatening diseases, where preliminary clinical evidence shows that the medicine may provide substantial improvement over existing therapies.
Breakthrough Therapy Designation was granted to Daratumumab based on data from two phase 3 studies:
The MMY3004 ( CASTOR ) clinical trial evaluating Daratumumab in combination with Bortezomib and Dexamethasone, compared to Bortezomib and Dexamethasone alone, in patients with multiple myeloma who received at least one prior therapy. Overall, the Daratumumab combination therapy demonstrated a reduction in the risk of disease progression or death.
The MMY3003 ( POLLUX ) clinical trial evaluating Daratumumab in combination with Lenalidomide and Dexamethasone, compared to Lenalidomide and Dexamethasone alone, in patients with multiple myeloma who received at least one prior therapy. Overall, the addition of Daratumumab reduced the risk of disease progression or death in these patients.
In November 2015, Darzalex was approved by the FDA for the treatment of patients with multiple myeloma who have received at least three 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. 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. In May 2013, Daratumumab received Breakthrough Therapy Designation from the FDA for this indication.
In May 2016, the European Commission ( EC ) granted conditional approval to Darzalex for monotherapy of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who have demonstrated disease progression on the last therapy.
Daratumumab 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 is also believed to induce tumor cell death through immunomodulatory effects.
Multiple myeloma is a blood cancer that occurs when malignant plasma cells grow uncontrollably in the bone marrow. Refractory cancer occurs when a patient's disease is resistant to treatment or in the case of multiple myeloma, patients progress within 60 days of their last therapy.
Accounting for approximately 1% of all cancers and 15 to 20% of haematologic malignancies worldwide, multiple myeloma is designated as an orphan disease in both the U.S. and Europe.
Globally, it is estimated that 124,225 people were diagnosed, and 87,084 died from the disease in 2015.
While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone fracture or pain, low red blood counts, fatigue, calcium elevation, kidney problems or infections.
Patients who relapse after treatment with standard therapies ( including proteasome inhibitors or immunomodulatory agents ) typically have poor prognoses and few remaining options. ( Xagena )
Source: Janssen, 2016
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