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BLINCYTO First Bispecific T Cell Engager (BiTE®) Antibody Construct Approved in European Union
THOUSAND OAKS, Calif., Nov. 23, 2015 – Amgen (NASDAQ:AMGN) today announced that the European Commission (EC) has granted conditional marketing authorization for BLINCYTO® (blinatumomab) for the treatment of adults with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-precursor acute lymphoblastic leukemia (ALL).
Experience the interactive Multimedia News Release here: http://www.multivu.com/players/English/7414058-amgen-blincyto-europe-approval/.
ALL is a rare and rapidly progressing cancer of the blood and bone marrow.1,2 For adults with relapsed or refractory ALL, the median overall survival is just three to five months.3 It is estimated that the incidence of adults with Ph- relapsed or refractory B-precursor ALL in the European Union (EU) is approximately 900 patients per year.4
“We are pleased the European Commission granted conditional marketing authorization for BLINCYTO,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “BLINCYTO has demonstrated efficacy in treating relapsed or refractory ALL, a very difficult-to-treat disease for which historically patients had limited therapeutic options. This approval represents an important milestone in immunotherapy research. BLINCYTO is the first clinical validation of the BiTE® platform, a new and innovative approach that helps the body’s own immune system fight cancer.”
The conditional marketing authorization for BLINCYTO is based on results of two Phase 2 studies, study ‘211 and ‘206. In the pivotal ‘211 trial, 42.9 percent of patients achieved complete remission (CR) or CR with partial hematological recovery (CRh*) with single-agent BLINCYTO.
The most serious adverse reactions that occurred during BLINCYTO treatment in the pivotal ‘211 trial included infections, neurologic events, neutropenia/febrile neutropenia, cytokine release syndrome and tumor lysis syndrome.
“We tested BLINCYTO in ALL, the most aggressive B-cell malignancy we know, and observed a clinically meaningful remission rate,” said Max S. Topp, M.D., professor, Hospital of Wuerzburg, Germany. “This is the first major advance in more than two decades for patients with this hard-to-treat cancer.”
“The prognosis for adult patients with ALL who are refractory to treatment or experience relapse is poor, and BLINCYTO constitutes a new treatment option for these patients,” said Hervé Dombret, M.D., professor, University Paris, Hospital Saint Louis, Paris. “It is important for clinicians and patients to have more treatment options in this acute form of leukemia.”
Approval from the EC grants a centralized conditional marketing authorization with unified labeling in the 28 countries that are members of the EU. Norway, Iceland and Liechtenstein, as members of the European Economic Area (EEA), will take corresponding decisions on the basis of the decision of the EC. Conditional license requires the license to be renewed every year and it will be converted to full standard license once post-licensing commitments have been fulfilled.
BLINCYTO was granted orphan drug designation by the European Medicines Agency in 2009 for the treatment of ALL.
About Study ‘211
Study ‘211 evaluated BLINCYTO in an open-label, multicenter, single-arm Phase 2 study. Eligible patients were at least 18 years of age with Ph- relapsed or refractory B-precursor ALL relapsed with first remission duration of less than or equal to 12 months in first salvage, or relapsed or refractory after first salvage therapy, or relapsed within 12 months of allogeneic hematopoietic stem cell transplantation (HSCT), and had at least 10 percent blasts in bone marrow.
The primary endpoint was the CR/CRh* rate within two cycles of BLINCYTO. Of the 189 patients evaluated in the trial, 42.9 percent (81/189; 95 percent CI, 35.7 - 50.2) achieved CR or CRh* within two cycles of treatment with BLINCYTO with the majority of responses (79 percent [64/81]) occurring within the first cycle of treatment. In a prespecified exploratory analysis, 82.2 percent (60/73) of minimal residual disease (MRD) evaluable patients with CR/CRh* also had an MRD response. The most common adverse reactions (greater than 20 percent) were infusion-related reactions (67.2 percent), infections (63 percent), pyrexia (59.8 percent), headache (34.4 percent), febrile neutropenia (28 percent), peripheral edema (25.9 percent), nausea (24.3 percent), hypokalemia (23.8 percent), constipation (20.6 percent) and anemia (20.1 percent). The most serious adverse reactions that occurred during BLINCYTO treatment included: infections (31.7 percent), neurologic events (16.4 percent), neutropenia/febrile neutropenia (15.3 percent), cytokine release syndrome (0.5 percent) and tumor lysis syndrome (0.5 percent).
About Study ‘206
Study ‘206 evaluated the safety and efficacy of BLINCYTO in an open-label, multicenter, dose-escalation Phase 2 study of 36 patients, who were at least 18 years of age with B-precursor ALL relapsed after at least induction and consolidation or having refractory disease with greater than 5 percent blasts in bone marrow, had an Eastern Cooperative Oncology Group (ECOG) performance status of at most 2, had a life expectancy of at least 12 weeks, and who did not have autologous HSCT within six weeks prior to start of treatment, allogeneic HSCT within three months prior to start of treatment, or previous treatment with BLINCYTO. The CR/CRh* rate was 69.4 percent (25/36) with 15 patients achieving CR (41.7 percent; 95 percent CI, 25.5 percent - 59.2 percent), and 10 patients achieving CRh* (27.8 percent; 95 percent CI, 14.2 percent - 45.2 percent). Of the patients with hematologic CR, 88 percent (22/25) also had MRD responses. Overall safety results from this study were consistent with the known BLINCYTO safety profile.
About Adult ALL in the Europe
The incidence of adult ALL in European countries is generally between 0.6 to 0.9 per 100,000 persons per year.5 In adult ALL, approximately 75 percent is B-precursor ALL, of which between 75-80 percent is Ph- and roughly half of adults will experience relapse or refractory disease.5 Thus, with a population projection of 416 million adults in the EU,6 it is estimated that the incidence of adult Ph- relapsed or refractory B-precursor ALL in the EU is approximately 900 patients per year.4
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.
About BiTE® Technology
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.
Important EU Product Safety Information
This product is subject to additional monitoring in the EU and EEA. All suspected adverse reactions should be reported in accordance with the national reporting system.
The adverse reactions described in this section were identified in the pivotal clinical study (N=189).The most serious adverse reactions that may occur during blinatumomab treatment include: infections (31.7%), neurologic events (16.4%), neutropenia/febrile neutropenia (15.3%) cytokine release syndrome (0.5%), and tumor lysis syndrome (0.5%). The most common adverse reactions were: infusion-related reactions (67.2%), infections (63.0%), pyrexia (59.8%), headache (34.4%), febrile neutropenia (28%), peripheral edema (25.9%), nausea (24.3%), hypokalaemia (23.8%), constipation (20.6%), anaemia (20.1%), cough (18.5%), diarrhea (18.0%), tremor (17.5%), neutropenia (17.5%), abdominal pain (16.9%), insomnia (15.3%), fatigue (15.3%), and chills (15.3%).
Please refer to the Summary of Product Characteristics for full European prescribing information.
This safety information is specific to the current U.S. approved indication.
BLINCYTO® is indicated for the treatment of Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).
This indication is approved under accelerated approval. Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials.
U.S. IMPORTANT SAFETY INFORMATION
WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES
BLINCYTO® is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.
Warnings and Precautions
U.S. Dosage and Administration Guidelines
Please see full U.S. Prescribing Information and medication guide for BLINCYTO at www.BLINCYTO.com.
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