Pharmaceutical Business review

FDA approves new indication for Amgen’s leukemia drug Blincyto

The approval is for patients whose minimal residual disease (MRD) is 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 (RFS).

Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

BLINCYTO, the first-and-only approved bispecific CD19-directed CD3 T cell engager (BiTE) immunotherapy, is now also the first-and-only therapy to be FDA-approved for MRD.

MRD refers to the presence of cancer cells that remain detectable, despite a patient's having achieved complete remission by conventional assessment.

MRD is only measurable through the use of highly sensitive testing methods that detect cancer cells in the bone marrow with a sensitivity of at least one cancer cell in 10,000 cells — versus about one in 20 with a conventional microscope-based evaluation.

Amgen translational sciences and oncology senior vice president David Reese said: "Until today, no therapy has been satisfactory in eradicating MRD or approved specifically to treat this high-risk patient population.

"This approval not only supports the use of BLINCYTO earlier in the ALL treatment continuum, but represents a paradigm shift in the management of ALL."

The University of Texas MD Anderson Cancer Center, Houston, department of leukemia associate professor Elias Jabbour said: "The detection of remaining cancer cells after a complete remission is the strongest prognostic factor for relapse in patients with ALL. It's critical to test for and know your patients' MRD status, because we know that treating to MRD-negativity will help to obtain better possible clinical outcomes for patients.

"In the BLAST study, blinatumomab led to no detectable cancer cells in approximately 80 percent of patients with MRD-positive ALL. This approval provides a much-needed treatment option to destroy the remaining detectable traces of leukemia."

The accelerated approval is based on results from the Phase 2 single-arm BLAST study (n=86), which found that BLINCYTO converted most patients to an MRD-negative state after a single cycle of therapy.

BLINCYTO met the primary endpoint, inducing a complete MRD response, which is no detectable MRD, in 81 percent of patients (95 percent CI: 71.6, 89.0). Median hematological RFS was 22.3 months.

Safety results among MRD-positive patients were consistent with the known safety profile of BLINCYTO in relapsed or refractory B-cell precursor ALL.

The most common adverse reactions (greater than 20 percent) were pyrexia, infusion related reactions, headache, infections (pathogen unspecified), tremor and chills.

The FDA-approved prescribing information for BLINCYTO includes a boxed warning for cytokine release syndrome and neurologic toxicities. BLINCYTO is also under a risk evaluation and mitigation strategy (REMS) program in the U.S.

Source: Company Press Release