Shire Receives Orphan Drug Designation for Gene Therapy Candidate SHP654 (BAX 888) for the Treatment of Hemophilia A

Shire Receives Orphan Drug Designation for Gene Therapy Candidate SHP654 (BAX 888) for the Treatment of Hemophilia A

October 25, 2017

SHP654 investigational new drug (IND) application accepted by the FDA

Lexington, MA – October 25, 2017 – Shire plc (LSE: SHP, NASDAQ: SHPG), the global biotechnology leader in rare diseases, today announced the U.S. Food and Drug Administration (FDA) awarded Orphan Drug Designation to Shire’s gene therapy candidate SHP654 (also designated as BAX 888), an investigational factor VIII (FVIII) gene therapy for the treatment of hemophilia A. The regulatory agency also granted Shire investigational new drug (IND) status for SHP654.

Orphan Drug Designation is intended to advance drug development for rare diseases.1 The FDA provides Orphan Drug Designation to drugs and biologics that are intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the U.S.1 Hemophilia A is the most common type of hemophilia, a bleeding disorder that causes longer-than-normal bleeding due to a lack of clotting factor VIII (FVIII) activity in the blood.2 It is estimated that approximately 14,000 people in the U.S. suffer from hemophilia A.3

“This important Orphan Drug Designation highlights Shire’s commitment to patients with rare diseases; and for hemophilia patients specifically our aim is to help them achieve zero bleeds,” says Paul Monahan, M.D., Senior Medical Director, Gene Therapy, Shire. “We know that hemophilia care is not one-size-fits-all and that every patient is unique, which is why we continue to focus on optimizing personal outcomes for hemophilia patients by developing innovations to transform care.”

Gene therapy is the delivery of a functional copy of the defective gene.4 For hemophilia, this is the gene for factor VIII or factor IX so the body can produce its own factor instead of relying on exogenous factor administration.5 The goal of hemophilia gene therapy is to provide a constant level of factor expression over several years and eliminate the peaks and troughs associated with factor replacement therapy.6 Shire is studying SHP654 as a potential treatment for hemophilia A patients through the delivery of a long-term, constant level of factor VIII expression.7

Shire also received FDA clearance for the IND application it submitted earlier this year to initiate a global multi-center study with SHP654 to evaluate the safety and optimal dose needed to boost factor VIII activity levels and affect hemophilic bleeding. The company anticipates that the SHP654 Phase 1/2 study will begin by the end of 2017.

About SHP654 (BAX 888)
Shire is developing SHP654, which includes technology acquired from Chatham Therapeutics, LLC, a spin-out of Asklepios Biopharmaceutical, Inc. SHP654 is an investigational factor VIII (FVIII) gene therapy intended to treat hemophilia A using a adeno-associated virus serotype 8 (AAV8) vector to deliver a codon-optimized, B-domain deleted FVIII (BDD-FVIII) specifically to a patient’s liver, where FVIII would then be produced and used to manage bleeds.7,8

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 activity in the blood.2 The severity of hemophilia A is determined by the amount of factor in the blood, with more severity associated with lower amounts of factor activity.9 More than half of patients with hemophilia A have the severe form of the condition.9 Hemophilia A primarily affects males, with an incidence of one in 5,000 male births.9,10


  1. U.S. Food and Drug Administration. Developing Products for Rare Diseases & Conditions FDA website. October 17, 2017
  2. World Federation of Hemophilia. “What is hemophilia?” World Federation of Hemophilia website. Accessed October 17, 2017.
  3. World Federation of Hemophilia. Report on the Annual Global Survey 2015. World Federation of Hemophilia website. Accessed October 17, 2017.
  4. U.S. Food and Drug Administration. What is Gene Therapy? FDA website Accessed October 17, 2017.
  5. National Hemophilia Foundation. Future Therapies. National Hemophilia Foundation website. Accessed October 17, 2017
  6. Herzog R. “Hemophilia Gene Therapy: Caught Between a Cure and an Immune Response.” Molecular Therapy. 2015;23(9):1411-1412.
  7. Falkner et al. “Development of SHP654 a highly efficient AAV8-based BDD-FVIII gene therapy vector for treatment of hemophilia A.” Available at:
  8. Hoellriegl et al. “Dose response and long-term expression of a human FVIII gene therapy construct in hemophilia A mice.” Available at:
  9. National Hemophilia Foundation. “Hemophilia A.” National Hemophilia Foundation website. Accessed October 17, 2017.
  10. Centers for Disease Control and Prevention. “Hemophilia.” Centers for Disease Control and Prevention website. Accessed October 17, 2017.

For further information please contact:

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About Shire
Shire is the leading global biotechnology company focused on serving people with rare diseases. 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.

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, 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.