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|FDA Grants Priority Review For Amgen's Supplemental Biologics License Application For BLINCYTO® (Blinatumomab)|
"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
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
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
About Study '205
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 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.
About BiTE® Technology
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
Warnings and Precautions
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).
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
Please see full U.S. Prescribing Information and medication guide for BLINCYTO® at www.BLINCYTO.com.
Amgen focuses on areas of high unmet medical need and leverages its biologics manufacturing expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.
No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for us to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and we expect similar variability in the future. Even when clinical trials are successful, regulatory authorities may question the sufficiency for approval of the trial endpoints we have selected. We develop product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as we may have believed at the time of entering into such relationship. Also, we or others could identify safety, side effects or manufacturing problems with our products after they are on the market.
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The scientific information discussed in this news release relating to new indications for our products is preliminary and investigative and is not part of the labeling approved by the
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