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

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


Lexington, MA – October 25, 2017 –Shire (LSE: SHP, NASDAQ: SHPG), the global biotechnology leader in rare diseases, today announced the 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.


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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.

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