FDA Grants Full Approval, Expands Indications for Blinatumomab in ALL

Blinatumomab is now fully approved as a treatment for relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) following FDA assessment of new trial data on survival outcomes and its use in certain clinical subgroups.

Amgen, which manufactures and sells blinatumomab as Blincyto, had previously received accelerated approval for blinatumomab after it was designated a breakthrough therapy, but later submitted a supplemental Biologics License Application (sBLA) to the FDA upon publication of results from 2 studies, according to an Amgen press release. In light of this new evidence, the FDA’s announced approval means the therapy is now fully approved for relapsed/refractory B-cell precursor ALL in both adults and children.

The sBLA included results from the Phase 3 TOWER study, which supported blinatumomab’s superior efficacy, as measured by overall survival (OS), against standard of care chemotherapy. Median OS was 7.7 months in the blinatumomab arm, compared with 4 months for the chemotherapy group. The findings from TOWER, which was concluded earlier than planned due to the abundant evidence in favor of blinatumomab, were published this March in the New England Journal of Medicine.

The application also incorporated data on remission outcomes among patients with Philadelphia chromosome-positive (Ph+) relapsed or refractory B-cell precursor ALL. In a phase 2 trial, the ALCANTARA study, blinatumomab was found effective in the study group of 45 adults, based on a combination of remission rate, complete remission duration, and proportion of patients with complete remission within 2 cycles of the blinatumomab infusion regimen.

Blinatumomab is a unique therapy in several respects, according to Amgen’s statement. The new approval makes it the first single-agent immunotherapy indicated for patients with Ph+ relapsed/refractory B-cell precursor ALL. It is also the first and only immunotherapy of its kind to be approved by the FDA, as it is a CD19-directed CD3 bispecific T cell engager (BiTE), and the first bispecific antibody construct to emerge from Amgen’s BiTE initiative.

The therapy’s prior designation as a breakthrough therapy and subsequent accelerated approval are partly due to the otherwise short survival times of patients it is intended to treat and the shortage of other therapy options. As mentioned in the TOWER findings, median survival time for patients receiving the current standard of care, chemotherapy, was just 4 months.

Now, blinatumomab’s full approval by the FDA could give patients with these high-risk clinical characteristics another treatment option, “marking a significant milestone for certain patients with relapsed or refractory ALL,” said Sean E. Harper, MD, Amgen’s executive vice president of Research and Development, in the statement. “This approval supports the use of BLINCYTO in a broader spectrum of patients, including those with few options to date, such as Philadelphia chromosome-positive patients, and reinforces the potential of the BiTE platform as a novel approach to immuno-oncology.”

The press statement noted that 6 adverse events occurred in the TOWER study’s treatment arm at a rate at least 5% higher than they had in the chemotherapy arm. The FDA will require the therapy to carry a boxed warning for cytokine release syndrome and neurologic toxicities. Amgen must also implement a plan to educate providers and pharmacists of these risks as part of the FDA-required Risk Evaluation and Mitigation Strategy.