New Formulation of ONCASPAR® (pegaspargase) Receives Marketing Authorization in Europe for Patients with Acute Lymphoblastic Leukemia (ALL)
Freeze-dried, or lyophilized, formulation aims to improve supply management
by providing the same dosing regimen as liquid ONCASPAR,
but with a three-times longer shelf life of up to 24 months
Zug, Switzerland - December 13, 2017 - Shire plc (LSE: SHP, NASDAQ: SHPG), the global leader in rare diseases, today announced that the European Commission (EC) granted Marketing Authorization for lyophilized ONCASPAR (pegaspargase), as a component of antineoplastic combination therapy in acute lymphoblastic leukemia (ALL) in pediatric patients from birth to 18 years, and in adult patients. The approval - which authorizes Shire to market lyophilized ONCASPAR in the 28 member states of the European Union (EU), as well as Iceland, Liechtenstein and Norway - follows a positive opinion adopted by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) on October 12.
"This approval underscores Shire's commitment to patients with acute lymphoblastic leukemia through continued research and evolution of asparaginase therapy," said Howard B. Mayer, M.D., SVP and ad-interim Head, Global Research and Development, Shire. "With this lyophilized formulation, we aim to make pegylated asparaginase, part of the pediatric standard therapy in acute lymphoblastic leukemia, available to patients in countries where liquid ONCASPAR is not currently offered. Additionally, with extended shelf life up to 24 months, treatment centers will have flexibility in inventory management to help ensure continuous treatment supply for patients."
Lyophilized ONCASPAR builds on more than a decade of data and research with liquid ONCASPAR, a pegylated asparaginase, and works the same way as the liquid formulation. By depleting serum L-asparagine levels and thereby interfering with protein synthesis, ONCASPAR deprives lymphoblasts of L-asparagine, resulting in cell death.,,
The new lyophilized formulation offers the same dosing regimen as liquid ONCASPAR, but with a three-times longer shelf life than the liquid formulation. Asparaginase is a critical component of the treatment regimen for ALL patients as it is a proven approach to inducing leukemic cell death.,,
Shire expects lyophilized ONCASPAR to be available in European markets beginning in the first half of 2018.
About Acute Lymphoblastic Leukemia
Acute lymphoblastic leukemia (ALL) is a cancer of the white blood cells and is characterized by an overproduction and accumulation of lymphoblasts, immature white blood cells. ALL is the most common type (~75%) of cancer among children diagnosed with leukemia. ALL can be curable within certain pediatric patient populations, with a five-year overall survival rate of 96% in children treated with regimens including ONCASPAR.
In Europe, ONCASPAR is indicated as a component of antineoplastic combination therapy in acute lymphoblastic leukemia (ALL) in pediatric patients from birth to 18 years, and adult patients.
Safety Information in Europe
ONCASPAR is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients, in patients with severe hepatic impairment, and in patients with a history of serious thrombosis, pancreatitis, or serious hemorrhagic events with prior L-asparaginase therapy.
Anaphylaxis or serious allergic reactions can occur; therefore, patients should be observed for 1 hour after administration having resuscitation equipment ready. Discontinue ONCASPAR in patients with serious allergic reactions. There have been reports of adverse reactions of pancreatitis. If pancreatitis is suspected ONCASPAR should be discontinued. ONCASPAR should also be discontinued in patients with serious thrombotic events.
Combination therapy with ONCASPAR can result in hepatic toxicity and central nervous system toxicity. In the presence of symptoms of hyperammonemia (e.g. nausea, vomiting, lethargy, irritation), ammonia levels should be monitored closely.
Very common adverse reactions reported in clinical trial data and the post-marketing experience of ONCASPAR in ALL patients include: hyperglycemia, pancreatitis, diarrhea, abdominal pain, nausea; hypersensitivity, urticaria, anaphylactic reactions; weight decreased; decreased appetite; rash.
Common adverse reactions include: febrile neutropenia, anemia, thrombosis; vomiting, stomatitis; hepatotoxicity, fatty liver; infections, sepsis; amylase increased, alanine aminotransferase increased, blood bilirubin increased, blood albumin decreased, neutrophil count decreased, platelet count decreased, activated partial thromboplastin time prolonged, prothrombin time prolonged, hypofibrinogenemia; hypertriglyceridemia, hyperlipidemia, hypercholesterolemia; pain in extremities; seizure, peripheral motor neuropathy, syncope; hypoxia; thrombosis.
For further information please contact:
|Ian Karpfirstname.lastname@example.org||+1 781 482 9018|
|Robert Coatesemail@example.com||+44 203 549 0874|
|Gwen Fisherfirstname.lastname@example.org||+1 781 482 9649|
|Annabel Cowperemail@example.com||+41 44 878 6638|
NOTES TO EDITORS
Shire is the global leader in serving patients with rare diseases. We strive to develop best-in-class therapies across a core of rare disease areas including hematology, immunology, genetic diseases, neuroscience, and internal medicine with growing therapeutic areas in ophthalmics and oncology. Our diversified capabilities enable us to reach patients in more than 100 countries who are struggling to live their lives to the fullest.
We feel a strong sense of urgency to address unmet medical needs and work tirelessly to improve people's lives with medicines that have a meaningful impact on patients and all who support them on their journey.
Statements included herein that are not historical facts, including without limitation statements concerning future strategy, plans, objectives, expectations and intentions, the anticipated timing of clinical trials and approvals for, and the commercial potential of, inline or pipeline products, are forward-looking statements. Such forward-looking statements involve a number of risks and uncertainties and are subject to change at any time. In the event such risks or uncertainties materialize, Shire's results could be materially adversely affected. The risks and uncertainties include, but are not limited to, the following:
- Shire's products may not be a commercial success;
- increased pricing pressures and limits on patient access as a result of governmental regulations and market developments may affect Shire's future revenues, financial condition and results of operations;
- Shire conducts its own manufacturing operations for certain of its products and is reliant on third party contract manufacturers to manufacture other products and to provide goods and services. Some of Shire's products or ingredients are only available from a single approved source for manufacture. Any disruption to the supply chain for any of Shire's products may result in Shire being unable to continue marketing or developing a product or may result in Shire being unable to do so on a commercially viable basis for some period of time;
- the manufacture of Shire's products is subject to extensive oversight by various regulatory agencies. Regulatory approvals or interventions associated with changes to manufacturing sites, ingredients or manufacturing processes could lead to, among other things, significant delays, an increase in operating costs, lost product sales, an interruption of research activities or the delay of new product launches;
- certain of Shire's therapies involve lengthy and complex processes, which may prevent Shire from timely responding to market forces and effectively managing its production capacity;
- Shire has a portfolio of products in various stages of research and development. The successful development of these products is highly uncertain and requires significant expenditures and time, and there is no guarantee that these products will receive regulatory approval;
- the actions of certain customers could affect Shire's ability to sell or market products profitably. Fluctuations in buying or distribution patterns by such customers can adversely affect Shire's revenues, financial conditions or results of operations;
- Shire's products and product candidates face substantial competition in the product markets in which it operates, including competition from generics;
- adverse outcomes in legal matters, tax audits and other disputes, including Shire's ability to enforce and defend patents and other intellectual property rights required for its business, could have a material adverse effect on the Company's revenues, financial condition or results of operations;
- inability to successfully compete for highly qualified personnel from other companies and organizations;
- failure to achieve the strategic objectives, including expected operating efficiencies, cost savings, revenue enhancements, synergies or other benefits at the time anticipated or at all with respect to Shire's acquisitions, including NPS Pharmaceuticals Inc., Dyax Corp. or Baxalta Incorporated may adversely affect Shire's financial condition and results of operations;
- Shire's growth strategy depends in part upon its ability to expand its product portfolio through external collaborations, which, if unsuccessful, may adversely affect the development and sale of its products;
- a slowdown of global economic growth, or economic instability of countries in which Shire does business, as well as changes in foreign currency exchange rates and interest rates, that adversely impact the availability and cost of credit and customer purchasing and payment patterns, including the collectability of customer accounts receivable;
- failure of a marketed product to work effectively or if such a product is the cause of adverse side effects could result in damage to Shire's reputation, the withdrawal of the product and legal action against Shire;
- investigations or enforcement action by regulatory authorities or law enforcement agencies relating to Shire's activities in the highly regulated markets in which it operates may result in significant legal costs and the payment of substantial compensation or fines;
- Shire is dependent on information technology and its systems and infrastructure face certain risks, including from service disruptions, the loss of sensitive or confidential information, cyber-attacks and other security breaches or data leakages that could have a material adverse effect on Shire's revenues, financial condition or results of operations;
- Shire incurred substantial additional indebtedness to finance the Baxalta acquisition, which has increased its borrowing costs may decrease its business flexibility; and
a further list and description of risks, uncertainties and other matters can be found in Shire's most recent Annual Report on Form 10-K and in Shire's subsequent Quarterly Reports on Form 10-Q, in each case including those risks outlined in "ITEM 1A: Risk Factors", and in Shire's subsequent reports on Form 8-K and other Securities and Exchange Commission filings, all of which are available on Shire's website.
All forward-looking statements attributable to us or any person acting on our behalf are expressly qualified in their entirety by this cautionary statement. Readers are cautioned not to place undue reliance on these forward-looking statements that speak only as of the date hereof. Except to the extent otherwise required by applicable law, we do not undertake any obligation to update or revise forward-looking statements, whether as a result of new information, future events or otherwise.
 Lyophilized Oncaspar Summary of Product Characteristics. European Medicines Agency.
 Oncaspar (pegaspargase) Summary of Product Characteristics. (SmPC) EU 1/2016.
 Wilson GJ, Bunpo P, Cundiff JK, et al. The eukaryotic initiation factor 2 kinase GCN2 protects against hepatotoxicity during asparaginase treatment. Am J Physiol Endocrinol Metab. 2013;305:E1124-1133.
 Story MD, Voehringer DW, Stephens LC, et al. L-Asparagainse kills lymphoma cells by apoptosis. Cancer Chemother Pharmacol. 1993;32:129-133.
 What is Childhood Leukemia? American Cancer Society. Available at: https://www.cancer.org/cancer/leukemia-in-children/about/what-is-childhood-leukemia.html. Accessed November 21, 2017.
 Place AE, Stevenson KE, Vrooman LM, et. al. Intravenous pegylated asparaginase versus intramuscular native Escherichia coli L-asparaginase in newly diagnosed childhood acute lymphoblastic leukaemia (DFCI 05-001): a randomised, open-label phase 3 trial. Lancet Oncol. 2015;16:1677-90.
The issuer of this announcement warrants that they are solely responsible for the content, accuracy and originality of the information contained therein.
Source: Shire plc via Globenewswire