U.S. FDA Accepts Shire’s Biologics License Application for Calaspargase Pegol (Cal-PEG) for Acute Lymphoblastic Leukemia (ALL)

U.S. FDA Accepts Shire’s Biologics License Application for Calaspargase Pegol (Cal-PEG) for Acute Lymphoblastic Leukemia (ALL)

February 28, 2018
  • If approved, Cal-PEG could provide a new PEGylated asparaginase first-line treatment for patients with ALL as well as an extended shelf life helping ensure availability to patients
  • ALL accounts for approximately 75 percent of childhood leukemia in the U.S.1

Cambridge, Mass. – February 28, 2018 – Shire plc (LSE: SHP, NASDAQ: SHPG), the global biotechnology leader in rare diseases, today announced that the U.S. Food and Drug Administration (FDA) has accepted the Biologics License Application (BLA) for Calaspargase Pegol (Cal-PEG; SHP663). The investigational-stage compound is being reviewed as a component of a multi-agent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia (ALL). The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of December 22, 2018 for Cal-PEG.

Shire is developing SHP663 based on more than a decade of data, research and experience with ONCASPAR® (pegaspargase), which is approved in the United States as a first-line treatment for patients with ALL.2 The mechanism of action of ONCASPAR is thought to be based on selective killing of leukemic cells due to the depletion of plasma asparagine, an amino acid that certain tumor cells depend on for growth and development.2 Asparagine depletion remains a cornerstone of ALL treatment regimens. Cal-PEG is also thought to be based on plasma L-asparagine depletion. The totality of the clinical trial data submitted to the FDA for review, as part of the BLA, included a comparable safety profile and efficacy outcomes to ONCASPAR. If approved, Cal-PEG could provide a treatment that has an extended shelf life beyond that of the current PEGylated asparaginase treatment, helping ensure availability to patients.

“Today’s FDA acceptance of the Cal-PEG BLA is an important milestone as we work to help address the unmet needs for rare and underserved cancers,” said Andreas Busch, Ph.D., Head of Research and Development at Shire. “Developing Cal-PEG underscores our commitment to evolving the standard of care in ALL, including taking innovative steps to improve treatment options for patients.”

The BLA filing is supported by data obtained in ALL patients treated with calaspargase pegol first-line as a component of a multi-agent chemotherapeutic regimen.

Acute Lymphoblastic Leukemia (ALL)
ALL is a cancer of the white blood cells and is characterized by an excess of lymphoblasts, an immature white blood cell. Lymphoblasts are normally found in the bone marrow but can be found in the blood and other locations in people with ALL. ALL accounts for about 75 percent of childhood leukemia in the U.S. and around 78 percent in Europe;1,3 however, it can be a curable disease.4

About Calaspargase Pegol
Calaspargase Pegol (Cal-PEG) is under review with the U.S. Food and Drug Administration (FDA) as a component of a multi-agent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia (ALL).

In the United States, ONCASPAR (pegaspargase) is indicated as a component of a multi-agent chemotherapeutic regimen for first-line treatment of patients with acute lymphoblastic leukemia (ALL) and for the treatment of patients with ALL and hypersensitivity to native forms of L-asparaginase.2

Select Important Safety Information2
ONCASPAR is contraindicated in patients with a history of: serious allergic reactions to ONCASPAR, history of the following with prior L-asparaginase therapy: serious thrombosis, pancreatitis or serious hemorrhagic events.

ONCASPAR Warning & Precautions include:

  • Anaphylaxis and Serious Allergic Reactions – observe patients for 1 hour after administration; discontinue if serious allergic reactions occur
  • Thrombosis – discontinue if serious thrombotic events occur
  • Pancreatitis – evaluate for pancreatitis in patients with abdominal pain; discontinue in patients with pancreatitis
  • Glucose Intolerance – monitor serum glucose
  • Coagulopathy and Hepatotoxicity – perform appropriate monitoring

The most common adverse reactions with ONCASPAR (≥2%) are allergic reactions (including anaphylaxis), hyperglycemia, pancreatitis, central nervous system (CNS) thrombosis, coagulopathy, hyperbilirubinemia and elevated transaminases. Hyperlipidemia (hypercholesterolemia and hypertriglyceridemia) has been reported in patients exposed to ONCASPAR.

For additional safety information, click for the full Prescribing Information:

For further information please contact:

Investor Relations  
Christoph Brackmann[email protected]+41 795 432 359
Sun Kim[email protected]+1 617 588 8175
Robert Coates[email protected]+44 203 549 0874
Gwen Fisher[email protected]+1 484 595 9836
Linda Calandra[email protected]+1 917 697 7543

About Shire

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.


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  • Shire’s products may not be a commercial success;
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  • the nature of producing plasma-based therapies may prevent Shire from timely responding to market forces and effectively managing its production capacity;
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  • failure to successfully execute or attain strategic objectives from Shire’s acquisitions and growth strategy may adversely affect the 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, could have negative consequences for Shire’s business and increase the risk of non-payment by Shire’s customers;
  • changes in foreign currency exchange rates and interest rates could have a material adverse effect on Shire’s operating results and liquidity;
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  • Shire faces risks relating to the expected exit of the United Kingdom from the European Union;
  • Shire incurred substantial additional indebtedness to finance the Baxalta acquisition, which has increased its borrowing costs and may decrease its business flexibility;
  • Shire's ongoing strategic review of its Neuroscience franchise may distract management and employees and may not lead to improved operating performance or financial results; there can be no guarantee that, once completed, Shire's strategic review will result in any additional strategic changes beyond those that have already been announced; 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 “ITEM1A: 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.

1 American Cancer Society. About Childhood Leukemia. Available at: https://www.cancer.org/cancer/leukemia-in-children/about/key-statistics.html.
2 ONCASPAR [package insert]. Cambridge, MA. Baxalta US, Inc.: 2017 Available at: http://www.shirecontent.com/PI/PDFs/ONCASPAR_USA_ENG.pdf.
3 Cancer Research UK. Children’s Leukaemia Incidence. Available at: http://www.cancerresearchuk.org/health-professional/cancer-statistics/childrens-cancers/incidence#heading-Four.
4 American Cancer Society. Survival Rates for Childhood Leukemias. Available at: https://www.cancer.org/cancer/leukemia-in-children/detection-diagnosis-staging/survival-rates.html.