Mississauga, ON. (January 12, 2016) – Amgen Canada Inc., today announced that Health Canada has granted conditional* approval of BLINCYTO™ (blinatumomab) for the treatment of adults with Philadelphia chromosome-negative (Ph-) relapsed or refractory B precursor acute lymphoblastic leukemia (ALL). With this approval, BLINCYTO™ becomes the first Health Canada-approved bispecific CD19-directed CD3 T-cell engager (BiTE®) antibody construct product, and the first single-agent immunotherapy to be approved for the treatment of patients with Ph- relapsed or refractory B precursor ALL, a rare and rapidly progressing cancer of the blood and bone marrow.1-3
“Health Canada’s conditional* approval of BLINCYTO™ underscores the need for new treatment options for patients with relapsed or refractory B precursor ALL, who are often young adults,” said Clive Ward-Able, M.D., executive director of Research and Development at Amgen Canada Inc. “BLINCYTO™ is the first clinical and regulatory validation of the BiTE® platform, an innovative approach that helps the body’s own immune system fight cancer.”
The conditional approval is received under Health Canada’s Notice of Compliance with conditions (NOC/c) policy which allows for earlier marketing of promising drugs for serious conditions before the drugs have definitively demonstrated clinical efficacy. Amgen has undertaken commitments to complete confirmatory trials to convert the approval to a full NOC.
“BLINCYTO represents a new treatment option for ALL patients and the first major advance in more than two decades for patients with this form of acute leukemia,” said Dr. Andre Schuh, M.D., F.R.C.P.(C), Department of Medical Oncology and Hematology at UHN/Princess Margaret Hospital/Ontario Cancer Institute. “As a clinician, having more treatment options for ALL patients who are refractory to treatment or experience relapse is an important development.”
Acute lymphoblastic leukemia (ALL) is a rare and rapidly progressing cancer of the blood and bone marrow — the spongy tissue inside bones where blood cells are made.2 The disease originates from immature blood cells, rather than mature ones.2
ALL occurs when a bone marrow cell develops mutations or errors in its DNA and instructs the cell to continue growing and dividing. Patients with ALL have abnormal white blood cells (lymphoblasts) that crowd out healthy white blood cells, red blood cells and platelets.2
In Canada, approximately 400 cases of ALL are diagnosed each year, more than half of whom are children.3,4 There are several subtypes of ALL, and among each subtype the projected incidence is even smaller.3,5 Adult patients diagnosed with Ph-ALL are particularly young, with a median age of 34 to 39 years.5,6,7
About BLINCYTO™ (blinatumomab)
BLINCYTO™ is the first BiTE® antibody construct and the first single-agent immunotherapy to be approved by Health Canada for relapsed or refractory B-cell precursor ALL. BLINCYTO™ qualified under Priority Review, and is now granted conditional* approval in Canada for the treatment of Philadelphia chromosome-negative (Ph-) relapsed or refractory B 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.
Clinical Trial Results1
The safety and efficacy of BLINCYTO were evaluated in an open-label, multicenter, single-arm study. Eligible patients were ≥ 18 years of age with Philadelphia chromosome-negative relapsed or refractory B-precursor ALL (relapsed with first remission duration of £ 12 months in first salvage or relapsed or refractory after first salvage therapy or relapsed within 12 months of allogeneic hematopoietic stem cell transplant (HSCT), and had ³ 10% blasts in bone marrow). The primary endpoint was the rate of complete remission or complete remission with partial hematologic recovery (CR/CRh*) within 2 cycles of treatment with BLINCYTO. Eighty-one out of 189 (42.9%) patients achieved CR/CRh* within the first 2 treatment cycles with the majority of responses (64 out of 81) occurring within cycle 1 of treatment. Thirty-two out of 189 (16.9%) patients underwent allogeneic HSCT in CR/CRh* induced with BLINCYTO. Numerically, patients with prior allogeneic HSCT had similar response rates to those without prior HSCT, and older patients had similar response rates to younger patients.
Important Safety Information1
BLINCYTO™ can cause Cytokine Release Syndrome (CRS) and Neurological Toxicities.
Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving BLINCYTO™. Infusion related reactions may be clinically indistinguishable from the manifestation of CRS. Patient should be observed closely for infusion reactions as well as signs and symptoms associated with CRS. Interrupt or discontinune BLINCYTO™ as recommended. 1
Neurological toxicities, which may be severe, life-threatening, or fatal, occurred in patients receiving BLINCYTO™. The median time to onset of a neurologic event was 9 days. Monitor patients and interrupt or discontinue BLINCYTO™ as recommended. Advise patients to not drive, operate heavy machinery, or do other dangerous activities while receiving BLINCYTO™.1
Serious infections, some of which were life-threatening or fatal, have been observed with BLINCYTO™. The fatal infections included sepsis, pneumonia, Fusarium infection, pneumonia fungal, septic shock, Aspergillus infection, bronchopneumonia, Candida infection, Enterococcal bacteraemia, Escherichia sepsis and lung infection. Monitor signs, symptoms, and laboratory parameters and treat appropriately. 1
The most common adverse reactions (≥ 20 percent) were pyrexia (60 percent), headache (34 percent), febrile neutropenia (28 percent), peripheral edema (26 percent), nausea (24 percent), hypokalaemia (24 percent), constipation (20 percent), and anemia (20 percent). The most common serious treatment-emergent adverse events (≥ 2%) included febrile neutropenia, pyrexia, sepsis, pneumonia, device-related infection, neutropenia, confusional state, tremor, encephalopathy, overdose, headache, staphylococcal bacteremia and other infections. Please visit www.amgen.ca for full product monograph. 1
Medication errors have been reported with BLINCYTO™. It is important to strictly follow instructions for preparation (including admixing) and administration to prevent overdose and underdose. 1
As a leader in innovation, Amgen Canada understands the value of science. With main operations located in Mississauga, Ont.’s vibrant biomedical cluster, and its research facility in Burnaby, B.C., Amgen Canada has been an important contributor to advancements in science and innovation in Canada since 1991. The company contributes to the development of new therapies and new uses for existing medicines in partnership with many of Canada’s leading health-care, academic, research, government and patient organizations. To learn more about Amgen Canada, visit www.amgen.ca.
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*This conditional authorization reflects the promising nature of the clinical evidence, which must be verified with further studies. Products approved under Health Canada's NOC/c policy, have demonstrated promising benefit, are of high quality and possess an acceptable safety profile based on a benefit/risk assessment
1. BLINCYTO™ Product Monograph; December 9, 2015
2. Mayo Clinic. Definition of acute lymphocytic leukemia. http://www.mayoclinic.org/diseases-conditions/acute-lymphocytic-leukemia/basics/definition/con-20042915 . Accessed December 17, 2015
3. Canadian Cancer Society. What is acute lymphocytic leukemia? http://www.cancer.ca/en/cancer-information/cancer-type/leukemia-acute-lymphocytic-all/acute-lymphocytic-leukemia/?region=on. Accessed December 17, 2015
4. Canadian Cancer Society. Acute Lymphocitic Leukemia Statistics. http://www.cancer.ca/en/cancer-information/cancer-type/leukemia-acute-lymphocytic-all/statistics/?region=on. Accessed December 17, 2015
5. Katz AJ, Chia VM, Schoonen WM , et al. Acute lymphoblastic leukemia: an assessment of international incidence, survival, and disease burden. Cancer Causes Control. 2015; 26 (11): 1627-1642. Retrieved from: http://link.springer.com/article/10.1007%2Fs10552-015-0657-6.
6. Kenderian SS, Al-Kali A, Gangat A, et al. Monosomal karyotype in Philadelphia chromosome-negative acute lymphoblastic leukemia. Blood Cancer Journal. 2013:3(122): 1-2.
7. Faderl S et al. Outcome of Philadelphia chromosome-positive adult lymphoblastic leukemia. Leukemia and Lymphoma. 2000;36(3-4):263-273.