THOUSAND OAKS, Calif., May 3, 2016 /PRNewswire/ -- Amgen (NASDAQ: AMGN) today announced that the U.S. 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 pediatric 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 Sept. 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.1-3 Of the approximately 2,500 U.S. children and adolescents diagnosed with B-cell precursor ALL each year, approximately 15-20 percent (375-500) will experience relapse or fail to achieve remission.4-7
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 pediatric 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.
About Study '205
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.
About BLINCYTO® (blinatumomab)
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 U.S. Food and Drug Administration, and is now approved in the U.S. 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.
About BiTE® Technology
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. For more information, visit www.biteantibodies.com.
BLINCYTO® U.S. Product Safety Information
Important Safety Information Regarding BLINCYTO® (blinatumomab) U.S. Indication
This safety information is specific to the current U.S. approved indication.
WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES
- Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving BLINCYTO®. Interrupt or discontinue BLINCYTO® as recommended.
- Neurological toxicities, which may be severe, life-threatening or fatal, occurred in patients receiving BLINCYTO®. Interrupt or discontinue BLINCYTO® as recommended.
BLINCYTO® is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.
Warnings and Precautions
Cytokine Release Syndrome (CRS): Life-threatening or fatal CRS occurred in patients receiving BLINCYTO®. Infusion reactions have occurred and may be clinically indistinguishable from manifestations of CRS. Closely monitor patients for signs and symptoms of serious events such as pyrexia, headache, nausea, asthenia, hypotension, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased total bilirubin (TBILI), disseminated intravascular coagulation (DIC), capillary leak syndrome (CLS), and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). Interrupt or discontinue BLINCYTO® as outlined in the Prescribing Information (PI).
Neurological Toxicities: Approximately 50% of patients receiving BLINCYTO® in clinical trials experienced neurological toxicities. Severe, life-threatening, or fatal neurological toxicities occurred in approximately 15% of patients, including encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders. The median time to onset of any neurological toxicity was 7 days. Monitor patients for signs or symptoms and interrupt or discontinue BLINCYTO® as outlined in the PI.
Infections: Approximately 25% of patients receiving BLINCYTO® experienced serious infections, some of which were life-threatening or fatal. Administer prophylactic antibiotics and employ surveillance testing as appropriate during treatment. Monitor patients for signs or symptoms of infection and treat appropriately, including interruption or discontinuation of BLINCYTO® as needed.
Tumor Lysis Syndrome (TLS): Life-threatening or fatal TLS has been observed. Preventive measures, including pretreatment nontoxic cytoreduction and on treatment hydration, should be used during BLINCYTO® treatment. Monitor patients for signs and symptoms of TLS and interrupt or discontinue BLINCYTO® as needed to manage these events.
Neutropenia and Febrile Neutropenia, including life-threatening cases, have been observed. Monitor appropriate laboratory parameters during BLINCYTO® infusion and interrupt BLINCYTO® if prolonged neutropenia occurs.
Effects on Ability to Drive and Use Machines: Due to the possibility of neurological events, including seizures, patients receiving BLINCYTO® are at risk for loss of consciousness, and should be advised against driving and engaging in hazardous occupations or activities such as operating heavy or potentially dangerous machinery while BLINCYTO® is being administered.
Elevated Liver Enzymes: Transient elevations in liver enzymes have been associated with BLINCYTO® treatment. The majority of these events were observed in the setting of CRS. The median time to onset was 15 days. Grade 3 or greater elevations in liver enzymes occurred in 6% of patients outside the setting of CRS and resulted in treatment discontinuation in less than 1% of patients. Monitor ALT, AST, gamma-glutamyl transferase (GGT), and TBILI prior to the start of and during BLINCYTO® treatment. BLINCYTO® treatment should be interrupted if transaminases rise to > 5 times the upper limit of normal (ULN) or if TBILI rises to > 3 times ULN.
Leukoencephalopathy: Although the clinical significance is unknown, cranial magnetic resonance imaging (MRI) changes showing leukoencephalopathy have been observed in patients receiving BLINCYTO®, especially in patients previously treated with cranial irradiation and anti-leukemic chemotherapy. Preparation and administration errors have occurred with BLINCYTO® treatment. Follow instructions for preparation (including admixing) and administration in the PI strictly to minimize medication errors (including underdose and overdose).
The most commonly reported adverse reactions (≥ 20%) in clinical trials were pyrexia (62%), headache (36%), peripheral edema (25%), febrile neutropenia (25%), nausea (25%), hypokalemia (23%), rash (21%), tremor (20%), diarrhea (20%) and constipation (20%).
Serious adverse reactions were reported in 65% of patients. The most common serious adverse reactions (≥ 2%) included febrile neutropenia, pyrexia, pneumonia, sepsis, neutropenia, device-related infection, tremor, encephalopathy, infection, overdose, confusion, Staphylococcal bacteremia, and headache.
U.S. Dosage and Administration Guidelines
BLINCYTO® is administered as a continuous intravenous infusion at a constant flow rate using an infusion pump which should be programmable, lockable, non-elastomeric, and have an alarm. It is very important that the instructions for preparation (including admixing) and administration provided in the full Prescribing Information are strictly followed to minimize medication errors (including underdose and overdose).
Please see full U.S. Prescribing Information and medication guide for BLINCYTO® at www.BLINCYTO.com.
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