Amgen Presents Data From Pivotal Phase 2 Study Of BLINCYTO (blinatumomab) Immunotherapy In Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia

December 9, 2014 |

16 min read

THOUSAND OAKS, Calif., Dec. 8, 2014 /PRNewswire/ -- Amgen (NASDAQ: AMGN) today announced that new data from a pivotal Phase 2 study evaluating BLINCYTO (blinatumomab) for the treatment of adult patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (ALL) was presented at the 56^th American Society of Hematology (ASH) Annual Meeting and Exposition.

In one analysis from the ‘211 study, 40 percent of patients treated with BLINCYTO who achieved a complete remission (CR) or complete remission with partial hematologic recovery (CRh) were enabled to proceed to allogeneic hematopoietic stem cell transplant (HSCT). Additionally, a secondary analysis from the study found that 82 percent of patients who had a CR or CRh also had a minimal residual disease (MRD) response, a measure used to predict disease recurrence in patients with ALL.

“The data from the ‘211 study expand the evidence of Amgen’s BiTE^® immunotherapy as an advance in the management of this difficult-to-treat cancer, and importantly, served as the basis for the recent U.S. Food and Drug Administration (FDA) approval of BLINCYTO,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “In this study, BLINCYTO helped patients bridge to a stem cell transplant after achieving a remission, a key goal in the management of ALL, and achieved MRD response in patients, an important parameter in predicting relapse.”

In the study, the most frequent grade >3 adverse events (AEs) occurring in >5 percent of patients were febrile neutropenia (25 percent), neutropenia (16 percent), anemia (14 percent), pneumonia (9 percent), thrombocytopenia (8 percent), hyperglycemia (8 percent), leukopenia (8 percent), alanine aminotransferase increased (7 percent), hypokalemia (7 percent), pyrexia (7 percent), sepsis (6 percent), hypophosphatemia (5 percent). Grade > 3 neurologic events occurred in 13 percent of patients, and grade > 3 cytokine release syndrome occurred in 2 percent of patients.

ASH Abstract 965: Allogeneic Hematopoietic Stem Cell Transplantation Following anti-CD19 BiTE^® Blinatumomab in Adult Patients with Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia
In one analysis of the ‘211 study, 40 percent of patients treated with BLINCYTO who achieved a CR or CRh were enabled to proceed to HSCT, including both patients who had received prior HSCT and patients who had not received prior HSCT. Additionally, the analysis found that responses to BLINCYTO were similar between patients who had received prior HSCT and patients who had not received HSCT (45 percent versus 42 percent, respectively).

ASH Abstract 3704: An Evaluation of Molecular Response in a Phase 2 Open-Label, Multicenter Confirmatory Study in Patients With Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia Receiving Treatment with the BiTE^® antibody construct Blinatumomab
A secondary analysis of the study demonstrated that, among patients receiving BLINCYTO who had a CR or CRh and had evaluable MRD data (n=73), 82 percent had an MRD response, with 70 percent of those patients achieving a complete MRD response. Median overall survival was longer among patients who had a CR or CRh and an MRD response compared to patients who didn’t have an MRD response (11.5 months [95 percent CI, 8.5 not estimable] versus 6.7 months [95 percent CI, 2.0 not estimable], respectively).

In the U.S., more than 6,000 cases of ALL will be diagnosed in 2014, and in the European Union, it is estimated that more than 7,000 cases of ALL are diagnosed each year.^1,2 In adult patients with relapsed or refractory ALL, median overall survival is just three to five months.³

‘211 Phase 2 Trial Design
The single arm, open-label, multicenter Phase 2 trial evaluated the safety and efficacy of BLINCYTO in adult patients with Philadelphia chromosome-negative (Ph-) B-precursor ALL who had relapsed or were refractory following treatment with standard front-line chemotherapy or allogeneic stem cell transplant. Patients received up to five four-week cycles of intravenous BLINCYTO treatment. The primary endpoint of the study was the rate of CR/CRh within the first two treatment cycles. Secondary endpoints include duration of CR and CRh, relapse-free survival, overall survival, HSCT realization rate, 100-day mortality rate and adverse events.

About BLINCYTO (blinatumomab)
BLINCYTO is the first BiTE® antibody construct and the first single-agent immunotherapy to be approved by the U.S. FDA.⁴ 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 acute lymphoblastic leukemia (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.

Important U.S. Product Information
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.

IMPORTANT SAFETY INFORMATION

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.

Contraindications
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 are 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. Follow instructions for preparation (including admixing) and administration in the PI strictly to minimize medication errors (including underdose and overdose).

Adverse Events
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%) and constipation (20%).

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 Prescribing Information and medication guide for BLINCYTO at www.BLINCYTO.com.

About Amgen
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 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 the world’s largest independent biotechnology company, 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.

Forward-Looking Statements
This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen Inc. and its subsidiaries (Amgen, we or us) and are subject to a number of risks, uncertainties and assumptions that could cause actual results to differ materially from those described. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission (SEC) reports filed by Amgen Inc., including Amgen Inc.'s most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and Form 8-K. Please refer to Amgen Inc.'s most recent Forms 10-K, 10-Q and 8-K for additional information on the uncertainties and risk factors related to our business. Unless otherwise noted, Amgen is providing this information as of Dec. 8, 2014, and expressly disclaims any duty to update information contained in this news release.

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CONTACT: Amgen
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¹ American Cancer Society. “Leukemia-Acute Lymphocytic.” Available at: http://www.cancer.org/cancer/leukemia-acutelymphocyticallinadults/detailedguide/leukemia-acute-lymphocytic-key-statistics. Accessed October 20, 2014.

² Gatta G, Maarten van der Zwan J, Casali P, et. al. Rare cancers are not so rare: The rare cancer burden in Europe. Eur J Cancer. 2011;47:2493-2511.

³Advani A.S. New immune strategies for the treatment of acute lymphoblastic leukemia: Antibodies and chimeric antigen receptors. Hematology Am Soc Hematol Educ Program. 2013;2013:131-7. Retrieved from: http://asheducationbook.hematologylibrary.org/content/2013/1/131.long. Accessed October 20, 2014.

⁴ NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Acute Lymphoblastic Leukemia. Version 1.2014. Available at: https://www.nccn.org/store/login/login.aspx?ReturnURL=http://www.nccn.org/professionals/physician_gls/pdf/all.pdf. Accessed on November 24, 2014.