Health Canada Approves Amgen's BLINCYTO (blinatumomab) For The Treatment Of Relapsed Or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia

BLINCYTO is the First-and-Only Bispecific CD19-Directed CD3 T-Cell Engager (BiTE^®) Immunotherapy Approved by Health Canada

MISSISSAUGA, ON, Jan. 12, 2016 /CNW/ - 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."

About ALL

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

About Amgen
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.

Forward-Looking Statements

This news release contains forward-looking statements that are based on management's current expectations and beliefs 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, including Amgen'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'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 January 12, 2016 and expressly disclaims any duty to update information contained in this news release.

No forward-looking statement can be guaranteed and actual results may differ materially from those Amgen Inc. and its subsidiaries (which are collectively referred to as we, or us) project. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for us and our partners to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and we expect similar variability in the future. We develop product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as we may have believed at the time of entering into such relationship. Also, we or others could identify safety, side effects or manufacturing problems with our products after they are on the market. Our business may be impacted by government investigations, litigation and product liability claims. If we fail to meet the compliance obligations in the corporate integrity agreement between us and the U.S. government, we could become subject to significant sanctions. We depend on third parties for a significant portion of our manufacturing capacity for the supply of certain of our current and future products and limits on supply may constrain sales of certain of our current products and product candidate development.

In addition, sales of our products (including products of our wholly-owned subsidiaries) are affected by the reimbursement policies imposed by third-party payers, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and healthcare cost containment as well as legislation affecting pharmaceutical pricing and reimbursement. Government and others' regulations and reimbursement policies may affect the development, usage and pricing of our products. In addition, we compete with other companies with respect to some of our marketed products as well as for the discovery and development of new products. We believe that some of our newer products, product candidates or new indications for existing products, may face competition when and as they are approved and marketed. Our products may compete against products that have lower prices, established reimbursement, superior performance, are easier to administer, or that are otherwise competitive with our products. In addition, while we and our partners routinely obtain patents for products and technology, the protection of our products offered by patents and patent applications may be challenged, invalidated or circumvented by our competitors and there can be no guarantee of our or our partners' ability to obtain or maintain patent protection for our products or product candidates. We cannot guarantee that we will be able to produce commercially successful products or maintain the commercial success of our existing products. Our stock price may be affected by actual or perceived market opportunity, competitive position, and success or failure of our products or product candidates. Further, the discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations. Our efforts to integrate the operations of companies we have acquired may not be successful.

The scientific information discussed in this news release related to our product candidates is preliminary and investigative. Such product candidates are not approved by Health Canada, and no conclusions can or should be drawn regarding the safety or effectiveness of the product candidates.

*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

References

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.

SOURCE Amgen Canada