New Data From Shire Aim To Help Close the Diagnosis and Treatment Gap for People With Hemophilia

ZUG, Switzerland, February 1, 2017 /PRNewswire/ --

Shire presentations at EAHAD 2017 underscore the company's leadership in improving global standards of care

Shire plc (LSE: SHP, NASDAQ: SHPG), the leading biotechnology company focused on serving individuals with rare diseases, presented its new estimate of the Global Annual Bleed Rate (GABR), an effort to build on current global metrics to measure the global burden of hemophilia.^[1] The GABR aims to identify regions of the world with the greatest need for improved diagnosis and access to approved treatment options for hemophilia patients.^[1] This initial presentation of the GABR model is one of 12 presentations from Shire at the 10th Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD), February 1-3, 2017 in Paris, France.

Initial findings from the GABR research presented at EAHAD show the incidence of hemophilia may be more than three times current global estimates and a bleeding episode occurs every three to 15 seconds worldwide.^[1] This finding builds on existing data showing only 25 percent of people living with hemophilia receive adequate treatment.^[2] The comprehensive findings from the model, which will be published in 2017, aim to help highlight the significant unmet needs that remain while expanding and improving strategies for hemophilia care around the world. (Estimating the Global Annual Bleed Rate in Haemophilia, http://onlinelibrary.wiley.com/doi/10.1111/hae.13150/full#hae13150-sec-0190.)^[1]

"We know thousands of hemophilia patients continue to bleed regularly, particularly in the most undertreated regions of the world, which impacts their joint health, quality of life and ability to work or go to school," said Alok Srivastava, MD, co-author of the GABR research and professor of medicine at the Christian Medical College, Vellore in India. "We must continue to invest in data collection, particularly patient reported outcomes such as ABR, to understand the true patient experience and drive important conversations about improving standards of care globally."

"Hemophilia patients across the world have complex needs and treatment goals that cannot be met with a one-size-fits-all approach," said Leonard Valentino, M.D., Global Head of Hematology Medical Affairs, Shire. "As the global leader in rare hematology, Shire is committed to innovative research on behalf of this community to help us focus efforts on improving care for patients."

Additional Shire Data at EAHAD 

Shire also presented data at EAHAD confirming the safety and efficacy profile of its factor replacement portfolio of treatments for patients with hemophilia. Notably, Shire presented new data from an analysis of a sequence identical analogue of one investigational agent, emicizumab, in combination with approved bypassing agents, FEIBA^® [Anti-Inhibitor Coagulant Complex] and recombinant (r)FVIIa, both treatments for hemophilia patients who develop an inhibitor.^[3] Results found a multi-fold increase in thrombin generation, indicating a potential thrombotic risk, for patients who receive the investigational agent combined with FEIBA or rFVIIa. (Synergistic Effects of a Procoagulant Bispecific Antibody and FEIBA or Factor VIIa on Thrombin Generation, http://onlinelibrary.wiley.com/doi/10.1111/hae.13158/full#hae13158-sec-0058.) ^[3]

In addition, Shire presented an update on its safety database describing 40 years of real-world safety experience with the bypassing agent FEIBA.^[4] A global review of safety databases for adverse event reports of FEIBA received from 1975 through July 2016 confirms the safety profile of FEIBA, showing that the reporting rate of treatment-associated thrombo-embolic events (TEEs) associated with FEIBA is comparable with previously reported data. (Four Decade Cumulative Review of Thrombo-Embolic Events Reported with the Use of Activated Prothrombin Complex Concentrate in Congenital Haemophilia, http://onlinelibrary.wiley.com/doi/10.1111/hae.13150/full#hae13150-sec-0012.)^[4]

About Hemophilia 

Hemophilia is a challenging chronic disease that causes longer-than-normal bleeding due to absent or deficient clotting factor in the blood.^[5] Hemophilia A is more common than hemophilia B;^[5] hemophilia A affects about 150,000 people, whereas hemophilia B affects about 30,000 people worldwide.^[6]

People with hemophilia, working closely with their healthcare professionals, can live healthy lives with proper care and adequate treatment.^[2] Treatment regimens typically include on-demand and/or regular prophylactic infusions of factor replacement therapy to control or prevent the risk of bleeding.^[5],[7]

Inhibitors are a rare but serious complication in patients with hemophilia.^[8] They form when the body's immune system attacks the molecules in factor therapy, causing it to be ineffective.^[8] Bypassing agents help bypass the inhibitor to help the body form a clot and stop bleeding.^[8]

About the Global Annual Bleed Rate (GABR) Model 

In collaboration with renowned hemophilia experts, Shire estimated the GABR to create a more comprehensive view of the burden of bleeding on hemophilia patients worldwide.^[1] By evaluating currently-available hemophilia data on prevalence and level of treatment, a literature-based model was developed to estimate the GABR at both the country and global levels. A full report of the GABR model is expected to be published later in 2017.^[1]

Safety Statement 

Please consult the FEIBA Summary Product Characteristics (SPC) before prescribing, particularly in relation to dosing and treatment monitoring.

Contraindications are hypersensitivity to the product, disseminated intravascular coagulation (DIC) and acute thrombosis or embolism (including myocardial infarction).

The Adverse Drug Reactions (ADRs) occurring in the highest frequency (common, ≥ 1/100 to <1/10) were hypersensitivity, headache, dizziness, hypotension, rash, hepatitis B surface antibody positive.

Other symptoms of hypersensitivity reactions to plasma-derived products include lethargy and restlessness.

Detailed Safety Statement  

Please consult the FEIBA Summary Product Characteristics (SPC) before prescribing, particularly in relation to dosing and treatment monitoring.

Contraindications 

Hypersensitivity to the product or any of the components, disseminated intravascular coagulation (DIC) and acute thrombosis or embolism (including myocardial infarction).

Special warnings and precautions for use 

Thromboembolic events, including disseminated intravascular coagulation (DIC), venous thrombosis, pulmonary embolism, myocardial infarction, and stroke, have occurred in the course of treatment with FEIBA. At the first signs or symptoms of thromboembolic events, the infusion should be stopped immediately and appropriate diagnostic and therapeutic measures initiated.

FEIBA can precipitate allergic-type hypersensitivity reactions; these reactions can be severe and can be systemic (e.g., anaphylaxis with urticaria and angioedema, bronchospasm, and circulatory shock). Other infusion reactions, such as chills, pyrexia, and hypertension have also been reported.

If clinically significant changes in blood pressure or pulse rate, respiratory distress, coughing or chest pain occur, the infusion is to be discontinued immediately and appropriate diagnostic and therapeutic measures are to be initiated.

In vitro tests, such as aPTT, whole blood clotting time (WBCT) may not correlate with the clinical picture.

Appropriate vaccination (hepatitis A and B) should be considered for patients in regular/ repeated receipt of human plasma-derived products including FEIBA.

Adverse Reactions 

   
    Common

    (greater than or
    equal to1/100 to  Hypersensitivity, Headache, Hypotension, Rash, Hepatitis B
    <1/10)            surface antibody positive.
    Not known         Disseminated intravascular coagulation (DIC), Increase of
                      inhibitor titer (anamnestic response),Urticaria, Anaphylactic
                      reaction, Paresthesia, Hypoaesthesia, Thrombotic stroke,
                      Embolic stroke, Somnolence, Dizziness, Dysgeusia, Cardiac
                      infarction, Tachycardia, Thrombosis, Venous thrombosis,
                      Arterial thrombosis, Embolism, Hypotension, Hypertension,
                      Flushing, Pulmonary embolism, Bronchospasm, Wheezing, Cough,
                      Dyspnea, Vomiting, Diarrhea, Abdominal discomfort, Nausea,
                      Sensation of numbness in the face, Angioedema, Urticaria,
                      Pruritus, Pain at the injection site, Malaise, Feeling hot,
                      Chills, Pyrexia, Chest pain, Chest discomfort, Blood pressure
                      decreased.

SHIRE and the Shire Logo are registered trademarks of Shire Pharmaceutical Holdings Ireland Limited or its affiliates.

FEIBA is a registered trademark of Baxalta Incorporated, a wholly owned, indirect subsidiary of Shire plc.

References 

1. Thompson C. et al. "Estimating the Global Annual Bleed Rate in Haemophilia." European Association for Haemophilia and Allied Disorders. Paris, France. February 1-3, 2017. Available at: http://onlinelibrary.wiley.com/doi/10.1111/hae.13150/full#hae13150-sec-0190
2. World Federation of Hemophilia. "About Bleeding Disorders: Treatment." World Federation of Hemophilia website. http://www.wfh.org/en/page.aspx?pid=642 . Accessed January 12, 2017.
3. Hartmann R. et al. "Synergistic Effects of a Procoagulant Bispecific Antibody and FEIBA or Factor VIIA on Thrombin Generation." European Association for Haemophilia and Allied Disorders. Paris, France. February 1-3, 2017. Available at: http://onlinelibrary.wiley.com/doi/10.1111/hae.13158/full#hae13158-sec-0058
4. Crea R. et al. "Four Decade Cumulative Review of Thrombo-Embolic Events Reported with the Use of Activated Prothrombin Complex Concentrate in Congenital Haemophilia." European Association for Haemophilia and Allied Disorders. Paris, France. February 1-3, 2017. Available at: http://onlinelibrary.wiley.com/doi/10.1111/hae.13150/full#hae13150-sec-0012
5. World Federation of Hemophilia. "What is hemophilia?" World Federation of Hemophilia website. http://www.wfh.org/en/page.aspx?pid=646. Accessed January 12, 2017
6. World Federation of Hemophilia. Report on the Annual Global Survey 2015. World Federation of Hemophilia website. http://www1.wfh.org/publication/files/pdf-1669.pdf. Accessed January 12, 2017.
7. National Hemophilia Foundation. "Hemophilia A". National Hemophilia Foundation website. https://www.hemophilia.org/Bleeding-Disorders/Types-of-Bleeding-Disorders/Hemophilia-A. Accessed January 12, 2017.
8. World Federation of Hemophilia. "What are inhibitors?" World Federation of Hemophilia website. http://www.wfh.org/en/page.aspx?pid=651. Accessed January 12, 2017.

NOTES TO EDITORS  

About Shire  

Shire is the leading global biotechnology company focused on serving people with rare diseases and other highly specialized conditions. We strive to develop best-in-class products, many of which are available in more than 100 countries, across core therapeutic areas including Hematology, Immunology, Neuroscience, Ophthalmics, Lysosomal Storage Disorders, Gastrointestinal / Internal Medicine / Endocrine and Hereditary Angioedema; and a growing franchise in Oncology.

Our employees come to work every day with a shared mission: to develop and deliver breakthrough therapies for the hundreds of millions of people in the world affected by rare diseases and other high-need conditions, and who lack effective therapies to live their lives to the fullest.

http://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, 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 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 combined 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 with respect to Shire's acquisition of NPS Pharmaceuticals, Inc., Dyax Corp. ("Dyax") or Baxalta Inc. ("Baxalta") 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 the 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 may decrease its business flexibility and increase borrowing costs;
• difficulties in integrating Dyax or Baxalta into Shire may lead to the combined company not being able to realize the expected operating efficiencies, cost savings, revenue enhancements, synergies or other benefits at the time anticipated or at all; and
• other risks and uncertainties detailed from time to time in Shire's filings with the Securities and Exchange Commission, including those risks outlined in "ITEM 1A: Risk Factors" in Shire's Quarterly Report on Form 10-Q for the quarter ended June 30, 2016.

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.

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