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THE FIRST-AND-ONLY BISPECIFIC CD19-DIRECTED CD3 T CELL ENGAGER (BiTE®) IMMUNOTHERAPY
Amgen Astellas BioPharma K.K. (Headquarters, Tokyo; President and Representative Director: Steve Sugino, “Amgen Astellas”) and Astellas Pharma Inc. (Headquarters, Tokyo; President and CEO: Kenji Yasukawa, Ph.D., “Astellas”) announced that Ministry of Health, Labour and Welfare has granted marketing approval for antineoplastic drug/bispecific antibody product
BLINCYTO® Drip Infusion 35μg (generic name: blinatumomab (Genetical Recombination)) for the treatment of relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).
BLINCYTO is the first-and-only bispecific T cell engager (BiTE®) immunotherapy construct approved globally. It is also the first approved immunotherapy from Amgen's BiTE® platform, an innovative approach that helps the body's immune system target cancer cells.
“Today’s approval of BLINCYTO marks a significant milestone that reinforces our commitment to addressing unmet medical needs of patients and physicians in Japan,” said Steve Sugino, president and representative director of Amgen Astellas. “As our first oncology treatment approved in Japan, we are proud to provide a much needed innovative treatment option for adults and children with relapsed or refractory B-cell ALL, one of the most aggressive B-cell malignancies.”
Hitoshi Kiyoi, M.D., Ph.D., professor of internal medicine, hematology and oncology, Nagoya University Graduate School of Medicine said, “The standard therapy for relapsed or refractory B-cell ALL has not been established in Japan and therefore different chemotherapy regimens have been selected, depending on the condition and background of each patient. BLINCYTO is a much needed and important new treatment option for patients with relapsed or refractory B-cell ALL, as demonstrated by the efficacy and survival benefit seen in the TOWER Study and it may enable effective bridging to allogenic hematopoietic stem cell transplant.”
The approval is based on data from multiple global studies, including the Phase 3 TOWER study and Japan Phase 1b/2 Horai study. In the TOWER study, BLINCYTO demonstrated a superior improvement in median overall survival (OS) versus standard of care (SOC) chemotherapy. Median OS was 7.7 months (95 percent CI: 5.6, 9.6) for BLINCYTO versus 4.0 months (95 percent CI: 2.9, 5.3) for SOC (HR for death=0.71; p=0.012). Safety results among subjects who received BLINCYTO were comparable to those seen in the previous Phase 2 studies of BLINCYTO in adult patients with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor ALL. In the TOWER study, major adverse reactions were pyrexia (39.0 percent), decrease in neutrophil count (14.6 percent), cytokine release syndrome (13.5 percent), febrile neutropenia (10.9 percent), headache (10.1 percent), elevated liver enzyme (10.1 percent) and decrease in platelet count (10.1 percent). In the Phase 1b/2 Horai study, BLINCYTO was administered to 35 Japanese adult and pediatric patients with relapsed or refractory B-cell precursor ALL. The safety results from the Horai study were comparable to those seen in the global studies, including TOWER. In the Horai study, major adverse reactions in adult patients were cytokine release syndrome (46.2 percent), pyrexia (46.2 percent), decrease in neutrophil count (38.5 percent) and decrease in platelet count (34.6 percent), and major adverse reactions in pediatric patients were elevated liver enzyme (66.7 percent), pyrexia (66.7 percent), cytokine release syndrome (55.6 percent) and abdominal pain (44.4 percent).
“As proof-of-concept for our unique bispecific T-cell engager technology, BLINCYTO has laid the groundwork for Amgen to deliver on our passion of addressing cancer by exploring numerous biologic pathways and therapeutic modalities,” said David M. Reese, M.D., executive vice president of Research and Development at Amgen. “This innovation is a good example of how we provide new options and hope to patients with serious illnesses like cancer. In bringing BLINCYTO to Japanese patients, we reinforce our commitment to deliver novel cancer therapies on behalf of patients worldwide.”
BLINCYTO is now approved in 57 countries, including the United States (U.S.), all member countries in the European Union (EU), and the European Economic Area, Canada and Australia.
About the TOWER Study
The TOWER study was a Phase 3, randomized, active-controlled, open-label study investigating the efficacy of BLINCYTO versus SOC chemotherapy in 405 adult patients with Ph- relapsed or refractory B-cell precursor ALL. The study enrolled a difficult-to-treat patient population which included patients with one or more relapses or refractory disease. In the BLINCYTO arm, this included 35 percent of patients that had relapsed post-allogenic hematopoietic stem cell transplant (alloHSCT) and excluded those with late first relapse (≥12 months after initial remission). Patients were randomized in a 2:1 ratio to receive BLINCYTO (n=271) or treatment with investigator choice of SOC chemotherapy (n=134). The determination of efficacy was based on OS. These results were published in The New England Journal of Medicine.1
About the Horai Study
The Horai study is a Phase 1b/2, single-arm, open-label study evaluating the safety and efficacy of BLINCYTO in Japanese adult and pediatric patients with relapsed or refractory B-cell precursor ALL. The primary endpoint for the Phase 1b portion was incidence of dose-limiting toxicities; the primary endpoint for the Phase 2 portion was complete remission or complete remission with partial hematologic recovery within 12 weeks of treatment with BLINCYTO. Secondary endpoints include duration of response, OS and relapse-free survival. An extension of the study is ongoing. For more information about this trial, please visit www.clinicaltrials.gov under trial identification number NCT02412306.
About ALL in Japan
ALL is a rapidly progressing cancer of the blood and bone marrow that occurs in both adults and children.2,3Japan is reported to have approximately 5,000 ALL patients, and it is estimated that of these, there are around 520 patients with relapsed or refractory ALL annually.4-7Adults with relapsed or refractory ALL typically have a very poor prognosis, with a median OS of three to five months.8Prognosis for children with ALL who are refractory or experience a relapse is extremely poor, and post-relapse survival is only achieved in 40-50 percent of patients. 9-11
BiTE®antibody constructs are a novel immuno-oncology technology that can be engineered to target any tumor antigen expressed by any type of cancer. The modified antibodies are designed to kill malignant cells using the patient's own immune system by bridging T cells to tumor cells. BiTE®antibody constructs help connect the T cells to the targeted cell, with the intent of causing T cells to inject toxins which trigger cancer cell death (apoptosis). Amgen is developing BiTE®antibody constructs to uniquely (or specifically) target numerous hematologic malignancies and solid tumors.
BLINCYTO is a bispecific CD19-directed CD3 T cell engager (BiTE®) immunotherapy that binds to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of effector T cells. BLINCYTO was granted breakthrough therapy and priority review designations by the U.S. Food and Drug Administration (FDA) in 2014, and carries full approval in the U.S. for the treatment of relapsed or refractory B-cell precursor ALL in adults and children. In the U.S., BLINCYTO is also approved under accelerated approval for the treatment of adults and children with B-cell precursor ALL in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1 percent.
BLINCYTO is approved in the EU for the treatment of Ph- relapsed or refractory B-cell precursor ALL in adults and children.
Important Japan Product Information
Relapsed or refractory B-cell acute lymphoblastic leukemia
Dosage and Administration:
In general, BLINCYTO®is administered as continuous intravenous infusion with the following dosing regimen for 28 days followed by a 14-day treatment-free interval. This constitutes one cycle and is repeated up to 5 cycles. After that, BLINCYTO® is administered with the following dosing regimen for 28 days followed by a 56-day treatment-free interval. This constitutes one cycle and is repeated up to 4 cycles. Of note, dose of BLINCYTO® can be reduced as appropriate depending on patient’s condition.
For more information, see the latest Japan Package Inserts.
About Amgen Astellas BioPharma
Amgen Astellas BioPharma K.K.（http://www.aabp.co.jp/jp/） is a Japanese company that began operations on October 1, 2013, to provide breakthrough-science-based medicines to help address unmet medical needs of patients in Japan. The company is a joint venture between Amgen, one of the world’s leading independent biotechnology companies, and Astellas Pharma Inc., a leading Tokyo-based R&D oriented global pharmaceutical company. AABP has grown into an organization with over 400 employees and comprehensive functions to be fully operational as a marketing authorization holder in Japan. The joint venture will become a wholly-owned Amgen affiliate as soon as 2020.
Astellas Pharma Inc., based in Tokyo, Japan, is a company dedicated to improving the health of people around the world through the provision of innovative and reliable pharmaceutical products. For more information, please visit our website at https://www.astellas.com/en.
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.
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.
For more information, follow us on www.twitter.com/amgenoncology
Cautionary Notes (Astellas)
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