Amgen announced the submission of a supplemental Biologics License Application (sBLA) to the US Food and Drug Administration (FDA) for Blincyto (blinatumomab) to include new data supporting the treatment of paediatric and adolescent patients with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor acute lymphoblastic leukaemia (ALL).

Blincyto, the first-and-only FDA-approved bispecific CD19-directed CD3 T cell engager (BiTE) immunotherapy, is currently available under an accelerated approval in the US for the treatment of Ph- relapsed or refractory B-cell precursor ALL, a rare and rapidly progressing cancer of the blood and bone marrow impacting both adults and children.

ALL is the most common type of cancer in children. While 95 per cent of children with ALL achieve a complete remission with first-line treatment, approximately 650 children in the US each year will relapse or be refractory to treatment. Paediatric patients with relapsed or refractory ALL have poor long-term outcomes, with an overall survival of less than 10 per cent. New approaches are needed to improve response rates and help certain patients meet eligibility requirements to receive an allogeneic haematopoietic stem cell transplantation (alloHSCT), the only potentially curative option for patients with relapsed or refractory disease.

"Children with relapsed or refractory ALL have very poor long-term outcomes and currently there are limited available therapies to induce remission," said Sean E. Harper, M.D., executive vice president of research and development at Amgen. "We look forward to collaborating with regulatory authorities to make Blincyto available to this ultra-orphan patient population with a high unmet medical need."

The sBLA is based on data from the phase 1/2 '205 single-arm trial, which found that treatment with Blincyto induced complete remission in a clinically meaningful number of paediatric patients with Ph- relapsed or refractory B-cell precursor ALL. Overall, the types of serious adverse events (AEs) reported in the paediatric population are consistent with the known Blincyto safety profile. The FDA approved prescribing information for Blincyto includes a boxed warning for cytokine release syndrome and neurologic toxicities.

Study '205 evaluated Blincyto in a phase 1/2 single-arm, multicenter, dose-finding, efficacy trial in patients less than 18 years of age with Ph- B-cell precursor ALL that was refractory, had relapsed at least twice or relapsed after an alloHSCT. Treatment in this study has been completed, and subjects are being monitored for long-term efficacy. The data will be submitted for publication.

The most frequently reported serious AEs were pyrexia, febrile neutropenia, cytokine release syndrome, sepsis, device-related infection, overdose, convulsion, respiratory failure, hypoxia, pneumonia and multi-organ failure.

Blincyto is a bispecific CD19-directed CD3 T cell engager (BiTE) antibody construct that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.

Blincyto was granted breakthrough therapy and priority review designations by the FDA, and is now approved in the US for the treatment of Ph- relapsed or refractory B-cell precursor ALL. This indication is approved under accelerated approval. Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials.

Blincyto was also recently granted conditional marketing authorization in the European Union for the treatment of adults with Ph- relapsed or refractory B-precursor ALL.

Bispecific T cell engager (BiTE) antibody constructs are a type of immunotherapy being investigated for fighting cancer by helping the body's immune system to detect and target malignant cells. The modified antibodies are designed to engage two different targets simultaneously, thereby juxtaposing T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. BiTE antibody constructs help place the T cells within reach of the targeted cell, with the intent of allowing T cells to inject toxins and trigger the cancer cell to die (apoptosis). BiTE antibody constructs are currently being investigated for their potential to treat a wide variety of cancers.

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