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BLINCYTO Almost Doubled Median Overall Survival in High-Risk Patients With B-Cell Precursor Acute Lymphoblastic Leukemia Compared to Standard of Care Chemotherapy
BLINCYTO is the First-and-Only Bispecific CD19-Directed CD3 T Cell Engager (BiTE®) Immunotherapy to Demonstrate Overall Survival Benefit in Patients With Philadelphia Chromosome-Negative Relapsed or Refractory Acute Lymphoblastic Leukemia
Results Published in The New England Journal of Medicine
THOUSAND OAKS, Calif. (March 1, 2017) – Amgen (NASDAQ:AMGN) today announced the New England Journal of Medicine published results from the Phase 3 TOWER study evaluating the efficacy of BLINCYTO® (blinatumomab) versus standard of care (SOC) chemotherapy in high-risk adult patients with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL), one of the most aggressive B-cell malignancies. Results from the analysis showed that median overall survival (OS) was 7.7 months (95 percent CI: 5.6, 9.6) for BLINCYTO versus four months (95 percent CI: 2.9, 5.3) for SOC (hazard ratio [HR] for death=0.71; p=0.012). The TOWER study is the confirmatory study for the Phase 2 trial that supported the U.S. Food and Drug Administration’s (FDA) accelerated approval designation for BLINCYTO in 2014.
BLINCYTO is a bispecific CD19-directed CD3 T cell engager (BiTE®) antibody construct. It is the first bispecific antibody construct from Amgen's BiTE® platform, which helps the body’s immune system target cancer cells and represents an entirely new area of oncology research. BiTE® antibody constructs are currently being investigated for their potential to treat a wide variety of cancers.
“Historically, patients with relapsed or refractory ALL have a poor prognosis, with an overall survival of just four months on standard of care chemotherapy," said Max S. Topp, M.D., professor and head of Hematology, University Hospital of Wuerzburg, Germany. "Findings from this head-to-head study showed that BLINCYTO almost doubled the median overall survival from four to 7.7 months, offering these high-risk patients a much needed alternative to chemotherapy that is both innovative and effective.”
The survival benefit for BLINCYTO was independent of allogeneic stem cell transplant (alloSCT), as the median OS, censored at the time of alloSCT, was 6.9 months for BLINCYTO versus 3.9 months for SOC. Improvement in OS was generally consistent regardless of age, prior salvage therapy or prior alloSCT. The magnitude of this benefit appeared greatest in earlier lines of salvage. Neutropenia and infection greater than or equal to grade 3 appeared less frequently with BLINCYTO compared to SOC, while neurological events appeared at a similar rate between arms.
"Adults with Ph- relapsed or refractory B-cell precursor ALL are in critical need of new treatment options," said Hagop M. Kantarjian, M.D., professor and chair of the Department of Leukemia at The University of Texas MD Anderson Cancer Center, Houston. “Results from the TOWER study reinforce the potential of this single agent bispecific T cell engager immunotherapy, which helped a higher percentage of patients achieve minimal residual disease response versus standard of care chemotherapy, highlighting the depth and quality of remissions achieved.”
Evaluation of key secondary endpoints showed that remission rates were also higher for BLINCYTO versus SOC. In the BLINCYTO group, 34 percent of patients achieved complete remission versus 16 percent in the SOC group. Patients receiving BLINCYTO also had a higher rate of combined complete remission or complete remission with partial or incomplete hematologic recovery (44 percent versus 25 percent).
Among patients with complete remission or complete remission with partial or incomplete hematologic recovery, 76 percent in the BLINCYTO group versus 48 percent in the SOC group achieved minimal residual disease (MRD) negative status, a measure of eradication of residual disease at the molecular level. Also among these patients, the median duration of remission was 7.3 months in the BLINCYTO group versus 4.6 months in the SOC group. For the key secondary efficacy endpoint of event-free survival, six month estimates in the BLINCYTO and chemotherapy groups were 30.7 percent and 12.5 percent, and the HR was 0.55 (95 percent CI: 0.43, 0.71), favoring BLINCYTO.
“As the first study of an immunotherapy to demonstrate overall survival benefit in adult patients with Ph- relapsed or refractory B-cell precursor ALL, TOWER represents an important advance in the understanding of this aggressive, ultra-orphan disease," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “As demonstrated by the data published today in the New England Journal of Medicine, BLINCYTO has proven to improve overall survival, extend remission rates and reduce minimal residual disease in these high-risk patients who previously have had limited effective options.”
Safety results among subjects who received BLINCYTO were comparable to those seen in the Phase 2 studies in adult patients with Ph- relapsed or refractory B-cell precursor ALL. For the most common adverse events (greater than or equal to 10 percent incidence rate) in the BLINCYTO arm, only three events (cough, pyrexia, cytokine release syndrome) occurred at an incidence rate that was at least 5 percent higher for BLINCYTO compared to SOC chemotherapy.
ALL is a rare and rapidly progressing cancer of the blood and bone marrow.1,2 Adult patients diagnosed with Ph- B-cell precursor ALL are often young, with a median age at diagnosis of 34-39.3,4 Currently, there is no broadly accepted standard treatment regimen for adult patients with relapsed or refractory ALL beyond chemotherapy.5 Adults with relapsed or refractory ALL typically have a very poor prognosis, with a median OS of three to five months.6
About the TOWER Study
The TOWER study was a Phase 3, randomized, open-label study investigating the efficacy of BLINCYTO versus SOC chemotherapy in 405 adult patients with Ph- relapsed or refractory B-cell precursor ALL. Patients were randomized in a 2:1 ratio to receive BLINCYTO (n=271) or treatment with investigator choice of one of four protocol-defined SOC chemotherapy regimens (n=134). The primary endpoint was OS. Key secondary endpoints included complete remission within 12 weeks, the combined endpoint of complete remission plus complete remission with partial or incomplete hematologic recovery and event-free survival. Other secondary endpoints included remission duration, MRD remission (
<10–4), alloSCT rate and adverse event rates.
The TOWER study is the confirmatory trial for BLINCYTO. Click here to read about the trial on ClinicalTrials.gov.
About Adult ALL
In the United States (U.S.), the incidence of adult ALL is approximately 0.9 per 100,000 persons per year.7 The incidence of adult ALL in European countries is generally between 0.6 to 0.9 per 100,000 persons per year.7 In adult ALL, approximately 75 percent is B-cell precursor ALL, of which 75-80 percent is Ph- and roughly half will be refractory to treatment or experience relapse.7 In the U.S., the incidence of adult Ph- relapsed or refractory B-cell precursor ALL was approximately 650 patients in 2015 and in the European Union (EU), the estimated incidence is approximately 1,200 patients per year.7,8
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 FDA, 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 EU for the treatment of adults with Ph- relapsed or refractory B-cell 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
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 Prescribing Information, including Boxed WARNINGS and Medication Guide, for BLINCYTO® at www.BLINCYTO.com.
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.
About Amgen's Commitment to Oncology
Amgen Oncology is committed to helping patients take on some of the toughest cancers, such as those that have been resistant to drugs, those that progress rapidly through the body and those where limited treatment options exist. Amgen's supportive care treatments help patients combat certain side effects of strong chemotherapy, and our targeted medicines and immunotherapies focus on more than a dozen different malignancies, ranging from blood cancers to solid tumors. With decades of experience providing therapies for cancer patients, Amgen continues to grow its portfolio of innovative and biosimilar oncology medicines.
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and leverages its 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.
For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.
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