CHMP recommends EU Marketing Authorization for Adynovi® [Antihemophilic factor (Recombinant), Pegylated] for adults and adolescents with Hemophilia A

If approved, ADYNOVI, built on ADVATE^® [Antihemophilic Factor (Recombinant)], would offer twice-weekly prophylactic dosing as well as on-demand control of bleeding episodes¹

Zug, Switzerland – November 13, 2017 – Shire plc (LSE: SHP, NASDAQ: SHPG), the world’s leading biotechnology company in rare diseases, announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending the granting of marketing authorization for ADYNOVI [Antihemophilic Factor (Recombinant), PEGylated], an extended half-life recombinant Factor VIII (rFVIII) treatment, for adults and adolescents ages 12 and older living with hemophilia A for on-demand and prophylactic use.¹

“This positive opinion marks an important step in providing adults and adolescents with hemophilia A in Europe with the potential for a new treatment option with a twice-weekly prophylaxis dosing schedule, so patients can manage their hemophilia A care with their physicians in the way that works best for them” said Howard B. Mayer, M.D., SVP and ad-interim Head, Global Research and Development, Shire.

The CHMP submission was based on outcomes from three Phase 3 clinical trials of patients with hemophilia A. These include a prospective, global, multi-centre, open label, non-randomized study of patients 12 to 65 years of age; a prospective, uncontrolled, open label, multi-centre study of patients 12 years of age and younger; and a study of perioperative control of hemostasis with interim study results from 15 patients with severe hemophilia A undergoing surgical procedures.^2,3,4  

Hemophilia A, a designated orphan disease by the European Commission (EC), is a rare bleeding disorder that causes longer-than-normal bleeding due to lack of clotting factor VIII (FVIII) in the blood.^5,6 Today, hemophilia A affects more than 150,000 people across the globe.⁷ It primarily affects males, with an incidence of one in 5,000 male births.⁸ Of the worldwide hemophilia patient population, an estimated 75 percent lack adequate treatment or access to treatment altogether.⁸

The CHMP’s Positive Opinion will be reviewed by the European Commission, which has the authority to grant marketing authorization in the EU.

About Hemophilia A
Hemophilia A, the most common type of hemophilia, is a rare bleeding disorder that causes longer-than-normal bleeding due to lack of clotting factor VIII (FVIII) in the blood.⁶ The severity of hemophilia A is determined by the amount of factor in the blood, with more severity associated with lower amounts of factor.⁹ More than half of patients with hemophilia A have the severe form of the condition.⁹

About ADYNOVI
ADYNOVI [Antihemophilic Factor (Recombinant), PEGylated] was first approved as ADYNOVATE^® by the Food and Drug Administration (FDA) in the U.S. followed by approval in Japan, Canada, and Colombia, and is approved as ADYNOVI in Switzerland.

For more information on ADYNOVI, please visit the EMA website.

U.S. IMPORTANT INFORMATION FOR ADYNOVATE

What is ADYNOVATE?

• ADYNOVATE is an injectable medicine that is used to help treat and control bleeding in children and adults with hemophilia A (congenital Factor VIII deficiency).
• Your healthcare provider may give you ADYNOVATE when you have surgery.
• ADYNOVATE can reduce the number of bleeding episodes when used regularly (prophylaxis). 

ADYNOVATE is not used to treat von Willebrand disease.

DETAILED IMPORTANT RISK INFORMATION

You should not use ADYNOVATE if you:

• Are allergic to mice or hamster protein
• Are allergic to any ingredients in ADYNOVATE or ADVATE [Antihemophilic Factor (Recombinant)]

Tell your healthcare provider if you are pregnant or breastfeeding because ADYNOVATE may not be right for you.

You should tell your healthcare provider if you:

• Have or have had any medical problems.
• Take any medicines, including prescription and non-prescription medicines, such as over-the-counter medicines, supplements or herbal remedies.
• Have any allergies, including allergies to mice or hamsters.
• Have been told that you have inhibitors to factor VIII (because ADYNOVATE may not work for you).

Your body may form inhibitors to Factor VIII. An inhibitor is part of the body’s normal defense system. If you form inhibitors, it may stop ADYNOVATE from working properly. Consult with your healthcare provider to make sure you are carefully monitored with blood tests for the development of inhibitors to Factor VIII.

You can have an allergic reaction to ADYNOVATE. Call your healthcare provider right away and stop treatment if you get a rash or hives, itching, tightness of the throat, chest pain or tightness, difficulty breathing, lightheadedness, dizziness, nausea or fainting.

The common side effects of ADYNOVATE are headache and nausea. Tell your healthcare provider about any side effects that bother you or do not go away.

For additional safety information, click here for Prescribing Information and discuss with your doctor.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

About ADVATE

ADVATE is currently approved in 69 countries worldwide, including the United States and 28 countries in the European Union.

EU IMPORTANT INFORMATION FOR ADVATE

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

Contraindications include hypersensitivity to the active substance or to any of the excipients listed in SmPC section 6.1 or to mouse or hamster proteins.

The ADRs that occurred in the highest frequency were development of neutralising antibodies to factor VIII (inhibitors), headache and pyrexia.

Hypersensitivity or allergic reactions have been observed rarely and may in some cases progress to severe anaphylaxis (including shock).

U.S. IMPORTANT INFORMATION FOR ADVATE

What is ADVATE?

• ADVATE is a medicine used to replace clotting factor (factor VIII or antihemophilic factor) that is missing in people with hemophilia A (also called “classic” hemophilia).
• ADVATE is used to prevent and control bleeding in adults and children (0-16 years) with hemophilia A. Your healthcare provider may give you ADVATE when you have surgery.
• ADVATE can reduce the number of bleeding episodes in adults and children (0-16 years) when used regularly (prophylaxis).

ADVATE is not used to treat von Willebrand disease.

For additional safety information, click here for Prescribing Information and discuss with your doctor.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

For further information please contact:

NOTES TO EDITORS

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.

www.shire.com

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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.

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References

1. European Medicines Agency. CHMP Summary of Opinion: Adynovi. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion_-_Initial_authorisation/human/004195/WC500238103.pdf. Last accessed November 2017.
2. Konkle BA, Stasyshyn O, Chowdary P, et al. Pegylated, full-length, recombinant factor VIII for prophylactic and on-demand treatment of severe hemophilia A. Blood. 2015;126:1078-85.
3. Mullins ES, Stasyshyn O, Alvarez-Román MT, et al. Extended half-life pegylated, full-length recombinant factor VIII for prophylaxis in children with severe haemophilia A. Haemophilia. 2017;23:238-246.
4. Brand B, Gruppo R, Wynn TT, et al. Efficacy and safety of pegylated full-length recombinant factor VIII with extended half-life for perioperative haemostasis in haemophilia A patients. Haemophilia. 2016;22:e251-8.
5. Orphanet. Rare disease registries in Europe. Orphanet Report Series: Rare Disease Collection, May 2017. Available at: http://www.orpha.net/orphacom/cahiers/docs/GB/Registries.pdf Last accessed October 2017.
6. World Federation of Hemophilia. What is hemophilia? Available at: http://www.wfh.org/en/page.aspx?pid=646 Last accessed October 2017. 
7. World Federation of Hemophilia. Report on the Annual Global Survey 2015. October 2016. Available at: https://www1.wfh.org/publication/files/pdf-1669.pdf Last accessed October 2017.
8. National Hemophilia Foundation. Fast facts. 2017. Available at: https://www.hemophilia.org/About-Us/Fast-Facts Last accessed October 2017.
9. National Hemophilia Foundation. Hemophilia A. Available at: https://www.hemophilia.org/Bleeding-Disorders/Types-of-Bleeding-Disorders/Hemophilia-A Last accessed October 2017.