Amgen said the European Commission has approved an expanded indication for Blincyto (blinatumomab) monotherapy to include adult patients with Philadelphia chromosome negative CD19 positive B-cell precursor acute lymphoblastic leukemia in first or second complete remission with minimal residual disease greater than or equal to 0.1 percent.
The approval was based on data from the phase II BLAST study in frontline and relapsed/refractory ALL, the largest prospective trial for MRD-positive ALL ever conducted. Blincyto, a bispecific CD19-directed CD3 T cell engager, is the first BiTE immunotherapy to receive regulatory approval globally.
In that study, Blincyto induced a complete MRD response, or no detectable MRD, in 78 percent of patients within one treatment cycle. Safety results among MRD-positive patients were consistent with the known safety profile of Blincyto in relapsed or refractory B-cell precursor ALL.
Approval via the centralized procedure allows for obtaining a marketing authorization from the EC, which is valid in all EU and European Economic Area-European Free Trade Association states, including Norway, Iceland and Liechtenstein.
In March 2018, FDA approved Blincyto for the treatment of adults and children with B-cell precursor ALL in first or second complete remission with MRD greater than or equal to 0.1 percent.
Blincyto is the first immunotherapy from Amgen’s BiTE platform. BiTE antibody construct technology, pioneered by Amgen, is an innovative treatment approach that helps the body’s immune system attack cancer cells without the removal of immune cells from the patient. Amgen is studying a number of “off-the-shelf” investigational BiTE immunotherapies, with distinct targets, across a range of hematologic and solid tumors.
The BLAST study is the largest ever prospective trial in patients with MRD-positive ALL. It is an open-label, multicenter, single-arm, phase II study evaluating the efficacy, safety and tolerability of Blincyto in adult patients with MRD-positive B-cell precursor ALL in complete hematologic remission after three or more cycles of intensive chemotherapy.
Patients received continuous IV infusion of Blincyto 15 µg/m2/d for four weeks, followed by two weeks off. Patients received up to four cycles of treatment and could undergo hematopoietic stem cell transplantation at any time after the first cycle, if eligible.
Efficacy was based on achievement of undetectable MRD within one cycle of Blincyto treatment and hematological relapse-free survival. Additional secondary endpoints included incidence and severity of adverse events, overall survival, time to hematological remission and duration of complete MRD response.
Blincyto is a bispecific CD19-directed CD3 T cell engager immunotherapy that binds to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of effector T cells. Blincyto was granted breakthrough therapy and priority review designations by the FDA in 2014, and carries full approval in the U.S. for the treatment of relapsed or refractory B-cell precursor ALL in adults and children.
In the U.S., Blincyto is also approved for the treatment of adults and children with B-cell precursor ALL in first or second complete remission with MRD greater than or equal to 0.1 percent. This indication is approved under accelerated approval based on MRD response rate and hematological relapse-free survival.
Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In the EU, Blincyto is indicated for the treatment of adults with Ph- relapsed or refractory B-precursor ALL and for the treatment of Ph- CD19 positive B-cell precursor ALL in first or second complete remission with MRD greater than or equal to 0.1 percent.
