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

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Monday, December 03, 2018

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CAMBRIDGE, Mass. - 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, 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 myPKFiTTM 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.

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

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.


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

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.


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


For more information on ADVATE, please visit

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 Accessed October 2018.
5. ADVATE Prescribing Information.


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Source: Shire Pharmaceuticals
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