The US Food and Drug Administration (US FDA) has granted Breakthrough Therapy Designation to Amgen's investigational bispecific T cell engager (BiTE) antibody blinatumomab, for adults with Philadelphia-negative (Ph-) relapsed/refractory B-precursor acute lymphoblastic leukaemia (ALL), a rapidly progressing cancer of the blood and bone marrow1.

The Breakthrough Therapy Designation was based on the results of a Phase 2 trial of 189 adult patients with Ph- relapsed/refractory B-precursor ALL treated with blinatumomab. Data from the Phase 2 trial were most recently presented at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) and the 19th Congress of the European Hematology Association (EHA).

There is a high unmet need for new medicines to treat relapsed and refractory ALL patients, who have very few treatment options," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "The results from the Phase 2 trial evaluating blinatumomab in adult patients with relapsed or refractory ALL are encouraging and provide a strong basis for a regulatory filing later this year and potential approval in this serious disease."

The FDA states that Breakthrough Therapy Designation is intended to expedite the development and review of drugs for serious or life-threatening conditions. The criteria for Breakthrough Therapy Designation require preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy. A Breakthrough Therapy Designation conveys all of the fast-track programme features, more intensive FDA guidance on an efficient drug development programme, an organisational commitment involving senior managers, and eligibility for rolling review and priority review2.

In the U.S. alone, it is estimated that over 6,000 cases of ALL were diagnosed in 2013, and in the European Union, more than 7,000 cases of ALL are diagnosed each year3,4. In adult patients with relapsed or refractory ALL, median overall survival is just three to five months.

Bispecific T cell engager (BiTE) antibodies are a type of immunotherapy being investigated for use in fighting cancer by helping to engage 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 antibodies help place the T cells within reach of the targeted cell, with the intent of allowing it to inject toxins and trigger the cell to die (apoptosis). BiTE antibodies are currently being investigated for their potential to treat a wide variety of cancers.

Blinatumomab is an investigational BiTE antibody designed to direct the body's cell-destroying T cells against target cells expressing CD19, a protein found on the surface of B-cell derived leukaemias and lymphomas. Blinatumomab is the first of the BiTE antibodies and Amgen has received orphan drug designation from the FDA for the treatment of ALL, chronic lymphocytic leukaemia (CLL), hairy cell leukaemia, prolymphocytic leukaemia and indolent B cell lymphoma and from the European Medicines Agency for the treatment of indolent B cell lymphoma, ALL, CLL and mantle cell leukaemia (MCL). Blinatumomab is also being investigated for its potential to treat paediatric relapsed/refractory ALL, relapsed/refractory Philadelphia positive (Ph+) B-precursor ALL, minimal residual disease positive (MRD+) B-precursor ALL, relapsed/refractory non-Hodgkin's lymphoma (NHL), including relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

Acute lymphoblastic leukaemia (ALL) is an  aggressive cancer of the blood and bone marrow the spongy tissue inside bones where blood cells are made1. The disease progresses rapidly and affects immature blood cells, rather than mature ones1. Worldwide, ALL accounts for more than 12 per cent of leukaemia. Of the 42,000 people diagnosed worldwide, 31,000 will die from the disease. Patients with ALL have abnormal white blood cells (lymphocytes) that crowd out healthy white blood cells, red blood cells and platelets, leading to infection, anemia (fatigue), easy bleeding and serious side effects6.