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Initial Data from Shire Collaboration Identifies Key Biomarkers That Affect Bleeding Patterns, Response to Treatment for Hemophilia A


Data from iPATH Collaboration to be presented at the American Society of Hematology’s 60th Annual Meeting

Cambridge, Mass. – December 1, 2018 – Shire plc (LSE: SHP, NASDAQ: SHPG), RCSI (The Royal College of Surgeons in Ireland), and Science Foundation Ireland (SFI), in collaboration with the Irish Haemophilia Society, today presented new data, from the novel clinical study called The Irish Personalised Approach to the Treatment of Haemophilia (iPATH), illustrating key drivers to implementing truly personalized care for people with hemophilia A during the 60th American Society of Hematology (ASH) Annual Meeting in San Diego, California.

Standard of care treatment for hemophilia A currently is prophylaxis with recombinant factor VIII (rFVIII) replacement therapy, an approach designed to minimize bleeding episodes using a weight-based dosing strategy.1 However, the half-life of factor VIII may vary markedly between individual patients, meaning some patients experience FVIII levels too low for sufficient protection from bleeds much earlier than others.2 As a result, even with prophylactic treatment, some people continue to experience bleeding events.2 This approach can be improved by integrating FVIII pharmacokinetics (PK) to produce an individualized treatment regimen.2

In a poster (Poster #1190) presented today at the ASH meeting, captured as part of the ongoing iPATH study, researchers found important biomarkers that influence bleeding risk in people with hemophilia, including a link between type O blood group and shorter half-life, and a link between age and longer half-life.2 The study also supports the feasibility of using limited, 2-sample PK profiling to capture accurate PK curves that can then be utilized to guide individualized, PK-guided prophylaxis.2 The 2-sample PK profiling was done through the use of myPKFiT for ADVATE® [Antihemophilic Factor (Recombinant)], a free web-based, Rx software for use with hemophilia A patients 16 and older weighing at least 45 kilograms and treated with ADVATE.3

The four-year iPATH program is open to all Irish children and adults with moderate or severe hemophilia.4 The study is supported by a Science Foundation Ireland (SFI) Strategic Partnership initiative and involves scientific researchers in RCSI, Trinity College Dublin (TCD) and Shire.4 The iPATH partnership includes the Irish Haemophilia Society, and clinical researchers based in St James’s Hospital Dublin, Our Lady’s Children’s Hospital Crumlin, Cork University Hospital and University Hospital Galway.4

“This research offers important insights about how we can apply personalized treatment planning for hemophilia as part of routine clinical care. By understanding the link between clinical parameters such as age or blood type, we can appreciate differences in PK and thus response to prophylactic care,” said study lead Professor James O’Donnell, Director of the Irish Centre for Vascular Biology, RCSI, and a Consultant Hematologist at the National Coagulation Center in St James’ Hospital, Dublin. “Importantly, this also supports the accuracy of simplified, 2-sample PK profiling, giving clinicians confidence that they can generate a reliable PK curve to guide individualized PK-guided dosing and minimize bleeds for their patients.”

“Every single bleed matters for people with hemophilia. Particularly if a joint or muscle bleed remains untreated, each one can lead to other long term consequences. So a core objective of this research is to better understand the specific characteristics of individuals that affect how and when they are likely to bleed,” said Peter Turecek, Senior Director, Global Medical Affairs, Shire. “If we can individualize treatment schedules by estimating PK curves through myPKFiT for ADVATE, we can further personalize treatment with the goal of getting as close as possible to zero bleeds.”

“I am very pleased to see such promising research results arising from the iPATH collaboration, a partnership that will positively impact treatment for patients of hemophilia around the world,” said Professor Mark Ferguson, Director General of Science Foundation Ireland and Chief Scientific Adviser to the Government of Ireland. “Improving medical approaches to this debilitating disease is crucial, and at Science Foundation Ireland we recognize the importance of funding scientific research that helps us to achieve that. I am confident that this research will provide further insights which will inform best practice for the future of hemophilia treatment, and I look forward to our continued work with Shire and RCSI.”

About the iPATH Collaboration

The Irish Personalised Approach to the Treatment of Haemophilia (iPATH) study is an ongoing collaboration investigating new personalized treatment approaches by tailoring care based on the needs of individual patients.4 Patients in Ireland with hemophilia are registered at a single National Coagulation Centre where data on the use of factor concentrates and bleeding rates have already been collected.4 This provides a unique opportunity to conduct a hemophilia study aimed at better understanding the underlying biology of hemophilia with the goal of developing a personalized approach to hemophilia care that can then potentially be extended to the global hemophilia community.4 This clinical study approach also has the potential to be adapted for other diseases.4

myPKFiT for ADVATE Indications for Use

The myPKFiT software is intended for use by licensed healthcare professionals (HCPs) who are familiar with hemophilia care. The myPKFiT software can be used to generate ADVATE dosage amount and frequency recommendations for routine prophylaxis for an individual patient 16 years of age and older and body weight of 45 kg or greater, using that patient's age and body weight information and local laboratory FVIII one-stage clotting activity measurements of sparse samples collected from that patient.3

A minimum of two sparse sampling points are required at the recommended 3-4 hours (± 30 minutes) and at 24-32 hours (±1 hour) post-infusion.

HCPs will also be able to evaluate various prophylaxis dose regimens tailored to an individual patient's needs and treatment plan.

The software output may be used to guide decisions on appropriate ADVATE dose and infusion intervals to maintain FVIII activity levels at or above a user specified minimum FVIII activity level between 1% to 3% above natural baseline for an individual patient in accordance with the FDA-approved dosing recommendations provided in the ADVATE Prescribing Information (PI).

myPKFiT should only be used to evaluate prophylactic dosing regimens for hemophilia A patients treated with ADVATE, as per the ADVATE Prescribing Information (PI).

myPKFiT for ADVATE is not indicated for the treatment of von Willebrand disease. myPKFiT for ADVATE should not be used for patients who have developed neutralizing antibody (inhibitor) to FVIII products.

myPKFiT for ADVATE software is Rx Only. For safe and proper use of the myPKFiT for ADVATE software, please refer to the complete instructions for use in the User Manual.

About ADVATE

ADVATE is a full-length (derived from the complete FVIII gene) recombinant FVIII product that is processed without any blood-based additives.5

ADVATE is currently approved in 69 countries worldwide, including the United States, Canada, 28 countries in the European Union, Algeria, Argentina, Australia, Brazil, Brunei, Chile, China, Colombia, Ecuador, Hong Kong, Iceland, India, Iraq, Israel, Japan, Kuwait, Macau, Malaysia, Mexico, Morocco, New Zealand, Norway, Panama, Puerto Rico, Qatar, Russia, Saudi Arabia, Serbia, Singapore, South Korea, Suriname, Switzerland, Taiwan, Tunisia, Turkey, Ukraine, Uruguay, and Venezuela.

ADVATE [Antihemophilic Factor (Recombinant)] Important Information

Indications

ADVATE is a recombinant antihemophilic factor indicated for use in children and adults with hemophilia A (congenital factor VIII deficiency) for:

  • Control and prevention of bleeding episodes.
  • Perioperative management.
  • Routine prophylaxis to prevent or reduce the frequency of bleeding episodes.

ADVATE is not indicated for the treatment of von Willebrand disease.

DETAILED IMPORTANT RISK INFORMATION

CONTRAINDICATIONS

Patients who have life-threatening hypersensitivity reactions, including anaphylaxis, to mouse or hamster protein or other constituents of the product.

WARNINGS & PRECAUTIONS

Hypersensitivity Reactions

Allergic-type hypersensitivity reactions, including anaphylaxis, have been reported with ADVATE. Symptoms include dizziness, paresthesia, rash, flushing, facial swelling, urticaria, dyspnea, pruritus, and vomiting. Discontinue ADVATE if hypersensitivity symptoms occur and administer appropriate emergency treatment.

Neutralizing Antibodies

Neutralizing antibodies (inhibitors) have been reported following administration of ADVATE predominantly in previously untreated patients (PUPs) and previously minimally treated patients (MTPs). Monitor all patients for the development of factor VIII inhibitors by appropriate clinical observation and laboratory testing. If expected plasma factor VIII activity levels are not attained, or if bleeding is not controlled with an expected dose, perform an assay that measures factor VIII inhibitor concentration.

ADVERSE REACTIONS

  • Serious adverse reactions seen with ADVATE are hypersensitivity reactions, including anaphylaxis, and the development of high-titer inhibitors necessitating alternative treatments to factor VIII.
  • The most common adverse reactions observed in clinical trials (>5% of subjects) were pyrexia, headache, cough, nasopharyngitis, arthralgia, vomiting, upper respiratory tract infection, limb injury, nasal congestion, and diarrhea.

Please see accompanying ADVATE full Prescribing Information available at http://www.shirecontent.com/PI/PDFs/ADVATE_USA_ENG.pdf

For more information on ADVATE, please visit www.ADVATE.com.

References:

  1. Valentino, LA et. Al. A randomized comparison of two prophylaxis regimens and a paired comparison of on-demand and prophylaxis treatments in hemophilia A management. Journal of Thrombosis and Haemostasis. 2012 Mar; 10(3): 359-367.
  2. Lavin, M et al. The Irish personalized approach to the treatment of haemophilia (iPATH) – determinants of inter-individual variation in FVIII pharmacokinetics, poster #1190. Presented at American Society of Hematology Annual Meeting 2018 on December 1st.
  3. myPKFiT Device User Manual. Baxter Healthcare Corporation; 2015.
  4. Shire. Newsroom. Novel clinical study collaboration announced designed to improve clinical care for hemophilia patients through innovative personalized treatment. Accessible at https://www.shire.com/en/newsroom/2017/december/5c9igj. Accessed October 2018.
  5. ADVATE Prescribing Information.

For further information please contact:

Investor Relations

Christoph Brackmannchristoph.brackmann@shire.com+41 41 288 41 29
Sun Kimsun.kim@shire.com+1 617 588 8175
Scott Burrowsscott.burrows@shire.com+41 41 288 4195
Media
Katie Joycekjoyce@shire.com+1 781 482 2779
Linda Calandralinda.calandra@shire.com+1 917 697 7543

NOTES TO EDITORS

About Shire

Shire is the global biotechnology leader serving patients with rare diseases and specialized conditions. We seek to push boundaries through discovering and delivering new possibilities for patient communities who often have few or no other champions. Relentlessly on the edge of what’s next, we are serial innovators with a diverse pipeline offering fresh thinking and new hope. Serving patients and partnering with healthcare communities in over 100 countries, we strive to be part of the entire patient journey to enable earlier diagnosis, raise standards of care, accelerate access to treatment, and support patients. Our diverse portfolio of therapeutic areas includes Immunology, Hematology, Genetic Diseases, Neuroscience, Internal Medicine, and Ophthalmics.

Championing patients is our call to action - it brings the opportunity - and responsibility - to change people’s lives.

www.shire.com

Forward-Looking Statements

Statements included herein that are not historical facts, including without limitation statements concerning future strategy, plans, objectives, expectations and intentions, projected revenues, 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 depends on third parties to supply certain inputs and services critical to its operations including certain inputs, services and ingredients critical to its manufacturing processes. 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;
  • the nature of producing plasma-based therapies 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;
  • failure to comply with laws and regulations governing the sales and marketing of its products could materially impact Shire’s revenues and profitability;
  • Shire’s products and product candidates face substantial competition in the product markets in which it operates, including competition from generics;
  • Shire’s patented products are subject to significant 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 Shire’s revenues, financial condition or results of operations;
  • Shire may fail to obtain, maintain, enforce or defend the intellectual property rights required to conduct its business;
  • Shire faces intense competition for highly qualified personnel from other companies and organizations;
  • failure to successfully execute or attain strategic objectives from Shire’s acquisitions and growth strategy 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, 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;
  • Shire is subject to evolving and complex tax laws, which may result in additional liabilities that may adversely affect Shire’s financial condition or results of operations;
  • if a marketed product fails to work effectively or causes adverse side effects, this could result in damage to Shire’s reputation, the withdrawal of the product and legal action against Shire;
  • 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 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;
  • the potential uncertainty among our employees, customers, suppliers, and other business partners resulting from the announcement by Takeda Pharmaceutical Company Limited on May 8, 2018 of a recommended offer for Shire under the UK Takeover Code; 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.

About RCSI

RCSI is ranked among the top 250 (top 2%) of universities worldwide in the Times Higher Education World University Rankings (2019) and its research is ranked first in Ireland for citations. It is an international not-for-profit health sciences institution, with its headquarters in Dublin, focused on education and research to drive improvements in human health worldwide. RCSI has been awarded Athena SWAN Bronze accreditation for positive gender practice in higher education.

About Science Foundation Ireland

Science Foundation Ireland funds oriented basic and applied research in the areas of science, technology, engineering, and mathematics (STEM) which promotes and assists the development and competitiveness of industry, enterprise and employment in Ireland. The Foundation also promotes and supports the study of and engagement with STEM and promotes an awareness and understanding of the value of STEM to society and, in particular, to the growth of the economy. See www.sfi.ie.

Science Foundation Ireland runs the #BelieveInScience campaign to promote the potential that science and discovery offer Ireland, today and in tomorrow’s world. The #BelieveInScience campaign sees Science Foundation Ireland work in partnership with the Irish research community to share a mutual passion for science with the public; to promote an understanding of the ability of science, technology, engineering and maths (STEM) to create positive change in the world and to drive a sustainable economy in Ireland.

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