First Immunostimulatory Antibody Approved in EU for Multiple Myeloma
European Commission (EC) approved Empliciti™ as a combination therapy with Revlimid® (lenalidomide) and dexamethasone for the patients who have earlier received at least one therapy. Empliciti™ gained EC approval on the basis of the remarkable results shown in Phase III study, ELOQUENT-2. It was a randomized, open label study in which Empliciti™ in combination with Revlimid® and dexamethasone (ERd) was compared with Revlimid® and dexamethasone (Rd) alone for progression free survival (PFS) and overall response rate (ORR).
53% relative improvement in PFS at three years was shown by administration of ERd compared to Rd alone. ERd demonstrated substantial improvement of 78.5% in ORR compared to 65.5% by Rd alone. ERd reduced the risk of disease progression by 32% versus Rd.
Elotuzumab is an immunostimulatory, humanized monoclonal antibody which received U.S. FDA Breakthrough Therapy designation in 2014. It is targeted against CS1 which is a cell surface glycoprotein receptor highly expressed on myeloma. CS1 is also called SLAMF7.
Mechanism of action of elotuzumab
Figure 1. Mechanisms of action of elotuzumab. (Photo credit: Liu et al., Dovepress, 2014, 4 Pages 15—27)
Elotuzumab’s Fc receptor binds simultaneously to Fc receptor (CD16) of Natural killer (NK) cells and CS1 of multiple myeloma (MM) and triggers antibody-dependent cellular cytotoxicity (ADCC) leading to MM cell killing. It can also directly activate immune system by interacting with CS1 on NK cells.
MM cells could also target various cellular or noncellular components of bone marrow (BM). Therefore, elotuzumab is also developed in a way to target and inhibit myeloma cells adhesion to BM stromal cells (BMSC).
Empliciti™ might be the luckiest immunostimulatory antibody to be first approved in EU for multiple myeloma but over the year, a flock of novel agents have been approved by U.S. FDA for treatment of multiple myeloma. Among them Novartis’ Farydak® (panobinostat) and Amgen’s Kyprolis® (carfilzomib) have been approved in EU.
Johnson & Johnson’s first human anti-CD38 monoclonal antibody, Darzalex® (daratumumab) and Takeda’s first and only oral proteasome inhibitor, Ninlaro® (ixazomib) are also FDA approved for multiple myeloma.
“At Bristol-Myers Squibb, we are committed to delivering pioneering medicines with the goal of revolutionizing the way cancer is treated for patients who inspire our work each and every day,” said Emmanuel Blin, senior vice president and head of Commercialization, Policy and Operations, Bristol-Myers Squibb. “With the approval of Empliciti in the EU, we are proud to extend our Immuno-Oncology science to multiple myeloma patients in Europe who have received at least one prior therapy”.
A sincere effort have been shown by the researchers to bring out novel therapeutic agents for the treatment of multiple myeloma and the EC approval of elotuzumab can be seen as a wide jump towards providing an improved life to the myeloma patients.
Featured image credit: European Union flag © Scanrail (Stock Photo ID: 95032196)