Amgen announced new data from a prespecified interim analysis of the phase 3 TOWER study, in which Blincyto (blinatumomab) demonstrated an almost two-fold increase in median overall survival (OS) compared to standard of care (SOC). The randomized, open-label TOWER study evaluated the efficacy of Blincyto versus SOC chemotherapy in adult patients with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

Results from the analysis showed that median OS was 7.7 months (95 per cent CI: 5.6, 9.6) for Blincyto versus 4 months (95 per cent CI: 2.9, 5.3) for SOC (stratified log-rank test p=.012; hazard ratio=0.71). As per the recommendation of an independent data monitoring committee, Amgen ended the study early for efficacy based on these results. The data will be presented during The Presidential Symposium at the 21st Congress of the European Hematology Association (EHA) in Copenhagen.

"Acute lymphoblastic leukaemia is the most aggressive type of B-cell malignancy," said Max S. Topp, M.D., professor and head of haematology, University Hospital of Wuerzburg, Germany. "The data presented today not only reinforce the potential of immunotherapy delivered by T cell engaging bispecific antibody constructs but also validate the efficacy of Blincyto in these heavily pretreated patients."

Improvement in OS was consistent across subgroups regardless of age, prior salvage therapy or prior allogeneic stem cell transplant (alloSCT). Serious adverse events included infection, blood and lymphatic system disorders, nervous system disorders and cytokine release syndrome. The Blincyto adverse events observed in the TOWER study were consistent with the known safety profile of Blincyto.

"This is the first study of an immunotherapy to demonstrate overall survival benefit in adult patients with Ph-negative B-cell precursor relapsed or refractory ALL, a very complex-to-treat disease with limited treatment options," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "Blincyto is currently approved for the treatment of Ph-negative B-cell precursor relapsed or refractory ALL under accelerated approval, and we look forward to working with regulatory authorities for a full approval for Blincyto in this patient population."

ALL is a rare and rapidly progressing cancer of the blood and bone marrow. Adult patients diagnosed with Ph- B-cell precursor ALL are often young, with a median age at diagnosis of 34-39. Currently, there is no broadly accepted standard treatment regimen for adult patients with relapsed or refractory ALL beyond chemotherapy. Adults with relapsed or refractory ALL typically have a very poor prognosis, with a median OS of three to five months.

The TOWER study was a phase 3, randomized, open-label study investigating the efficacy of Blincyto versus SOC chemotherapy in adult patients with Ph-relapsed or refractory B-cell precursor ALL. Patients were randomized in a 2:1 ratio to receive Blincyto or treatment with investigator choice of one of four protocol defined SOC chemotherapy regimens. The primary endpoint was OS. Secondary endpoints included complete remission and the combined endpoint of complete remission plus complete remission with partial or incomplete hematologic recovery.

The TOWER study is the confirmatory trial for Blincyto, and Amgen plans to file for full approval of Blincyto based on results from the study.

The incidence of adult ALL in European countries is generally between 0.6 to 0.9 per 100,000 persons per year. In the United States (US), the incidence of adult ALL is approximately 0.9 per 100,000 persons per year. In adult ALL, approximately 75 per cent is B-cell precursor ALL, of which 75-80 per cent is Ph- and roughly half will be refractory to treatment or experience relapse.  Thus, with a population projection of 416 million adults in the European Union (EU), it is estimated that the incidence of adult Ph-relapsed or refractory B-cell precursor ALL in the EU is approximately 900 patients per year.  In the US, the incidence was approximately 650 patients in 2015.

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 US Food and Drug Administration (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.

In November 2015 Blincyto was granted conditional marketing authorization in the EU for the treatment of adults with Ph- relapsed or refractory B-cell 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.