Amgen announced that the US Food and Drug Administration (FDA) has accepted for priority review the supplemental Biologics License Application (sBLA) 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 leukemia (ALL).
"Children and adolescents with ALL who experience a second or greater relapse or are refractory often have a dismal prognosis with survival rates below 10 percent," said Sean E. Harper, M.D., executive vice president of research and development at Amgen. "The FDA's acceptance of the sBLA submission for Blincyto reinforces immunotherapy as a potential option for children in need of new treatments to fight this complex disease and help prevent further relapse."
Priority review is assigned to applications for drugs that treat serious conditions and would, if approved, provide significant improvements in the safety or effectiveness of the treatment, diagnosis or prevention of serious conditions. The Prescription Drug User Fee Act (PDUFA) target action date is September 1, 2016.
ALL is a rare and rapidly progressing cancer of the blood and bone marrow impacting both adults and children and is the most common type of cancer in children. Of the approximately 2,500 US children and adolescents diagnosed with B-cell precursor ALL each year, approximately 15-20 per cent (375-500) will experience relapse or fail to achieve remission.
The sBLA is based on data from the phase 1/2 '205 single-arm trial, which evaluated Blincyto in pediatric patients with relapsed or refractory B-cell precursor ALL. The study met its phase 2 primary endpoint of complete remission within the first two cycles of Blincyto treatment. 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 B-cell precursor ALL that was refractory, had relapsed at least twice or relapsed after an allogeneic hematopoietic stem cell transplant (alloHSCT). Treatment in this study has been completed and subjects are being monitored for long-term efficacy. The data is being submitted for publication.
This study included a phase 1 dose-finding portion and a phase 2 portion evaluating safety and efficacy at the recommended dose (stepwise 5/15-µg/m²/day), which was proposed by an independent Data Safety Monitoring Board based on data from the dose-finding portion. The primary phase 1 endpoint was the maximum-tolerated dose, defined as the maximum dose at which =1 of six patients experienced a dose-limiting toxicity. Secondary endpoints included pharmacokinetics and incidence of AEs. The primary phase 2 endpoint was complete remission within the first two cycles of Blincyto treatment. Secondary endpoints included incidence of AEs, proportion undergoing alloHSCT after Blincyto treatment, relapse-free survival and overall survival. Minimal residual disease (MRD) response and complete MRD response were exploratory endpoints in both phases.
The most frequent grade =3 AEs among the 70 patients who received the recommended dose were anemia, thrombocytopenia, febrile neutropenia, hypokalemia and neutropenia.
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, 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 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.