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Shire submits investigational New Drug Application to FDA for Gene Therapy candidate SHP654 for treatment of Hemophilia A

Shire plc
Posted on: 06 Jul 17

Shire submits investigational New Drug Application to FDA for Gene Therapy candidate SHP654 for treatment of Hemophilia A

SHP654 aims to deliver sustained protection against bleeds for patients with hemophilia A

Lexington, Mass.   -   July 6, 2017   - Shire plc (LSE: SHP, NASDAQ: SHPG), the leading biotechnology company focused on serving people with rare diseases, today announced the submission of an investigational new drug (IND) application to the U.S. Food and Drug Administration (FDA) for SHP654, also designated as BAX 888, an investigational factor VIII (FVIII) gene therapy for the treatment of hemophilia A. SHP654 aims to protect hemophilia A patients against bleeds through the delivery of a long-term, constant level of factor expression. 1 The IND filing for SHP654 represents the latest step forward for Shire's gene therapy program, which shows promise for both hemophilia A and B populations.

"Shire is leveraging decades of scientific leadership in hemophilia to advance research in gene therapy for this community," said Paul Monahan, M.D., Senior Medical Director, Gene Therapy, Shire. "Drawing from our rich heritage, Shire is well equipped to sustainably support the development of gene therapies that aim to advance current standards of care and minimize the burden of this disease. SHP654 uses a proprietary technology platform designed to produce sustained levels of factor similar to the natural mechanisms of the body. Our goal with gene therapy for hemophilia is to uphold the highest standards for safety and efficacy."

Shire's gene therapy program for hemophilia A uses a recombinant adeno-associated virus serotype 8 (rAAV8) vector, which selectively targets the liver. 1,2 It involves the delivery of a functional copy of FVIII to the body's liver to enable its own production of FVIII, rather than relying on a factor-based treatment. 1 SHP654 uses the rAAV8 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. 1 The FVIII expression is further controlled in patients by incorporating the liver-specific transthyretin (TTR) promoter/enhancer. 1

The IND filing for SHP654 was based on the results of pre-clinical and phase 1 studies demonstrating the potential utility of this candidate, including the following that will be presented at the International Society on Thrombosis and Haemostasis (ISTH) 26th Biennial Congress in Berlin, Germany, from July 8 - 13, 2017:

  • Development of SHP654, a highly efficient AAV8-based BDD-FVIII gene therapy vector for treatment of hemophilia A . Session Title: Gene Therapy for Hemophilia: Clinical. Oral # OC 13.6.10th July, 17:45-19:00 CEST; Hall B 1
  • Integration site analysis in mice demonstrates excellent biosafety profile of a recombinant (r) FVIII adeno-associated virus (AAV8) gene therapy product. Session Title: Poster Session. Poster # PB 1094. 11th July, 12:00-13:15 CEST; Exhibition Hall 4.2 3
  • Dose response and long-term expression of a human FVIII gene therapy construct in hemophilia A mice. Session Title: Poster Session. Poster # PB 1101. 11th July, 12:00-13:15 CEST; Exhibition Hall 4.2 2
  • Nonclinical safety evaluation of a human FVIII gene therapy construct in mice. Session Title: Poster Session. Poster # PB 1099. 11th July, 12:00-13:15 CEST; Exhibition Hall 4.2 4

An IND is a request for FDA authorization to administer an investigational drug to humans. 5 Following the FDA's acceptance of the IND for SHP654, Shire will study SHP654 in a global multi-center study evaluating safety and examining the SHP654 doses required to boost factor VIII activity levels and affect hemophilic bleeding and will pursue bringing this innovation to markets worldwide.

About SHP654
Shire is developing SHP654 (BAX 888), 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 recombinant adeno-associated virus serotype 8 (rAAV8) 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. 1,2

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 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. 7 More than half of patients with hemophilia A have the severe form of the condition. 7 Approximately 25-30% of individuals with severe hemophilia A develop inhibitors. 8 Inhibitors are a serious medical problem that can occur when a person with hemophilia has an immune response to treatment with clotting factor concentrates. 9 Hemophilia primarily affects males, with an incidence of one in 5,000 male births. 7,10

References

  1. Falkner et al. "Development of SHP654 a highly efficient AAV8-based BDD-FVIII gene therapy vector for treatment of hemophilia A." International Society on Thrombosis and Haemostasis Congress. Berlin, Germany July 8-13, 2017. Available at: http://onlinelibrary.wiley.com/doi/10.1111/rth2.2017.1.issue-S1/issuetoc
  2. Hoellriegl et al. "Dose response and long-term expression of a human FVIII gene therapy construct in hemophilia A mice." International Society on Thrombosis and Haemostasis Congress. Berlin, Germany July 8-13, 2017. Available at: http://onlinelibrary.wiley.com/doi/10.1111/rth2.2017.1.issue-S1/issuetoc
  3. Hoellriegl et al. "Integration site analysis in mice demonstrates excellent biosafety profile of a recombinant ® FVIII adeno-associated virus (AAV8) gene therapy product." International Society on Thrombosis and Haemostasis Congress. Berlin, Germany July 8-13, 2017. Available at: http://onlinelibrary.wiley.com/doi/10.1111/rth2.2017.1.issue-S1/issuetoc
  4. Hoellriegl et al. "Nonclinical safety evaluation of a human FVIII gene therapy construct in mice." International Society on Thrombosis and Haemostasis Congress. Berlin, Germany July 8-13, 2017. Available at: http://onlinelibrary.wiley.com/doi/10.1111/rth2.2017.1.issue-S1/issuetoc
  5. U.S Food and Drug Administration. "Investigational New Drug (IND) or Device Exemption (IDE) Process (CBER)." U.S Food and Drug Administration website. https://www.fda.gov/biologicsbloodvaccines/developmentapprovalprocess/investigationalnewdrugindordeviceexemptionideprocess/default.htm . Accessed June 28, 2017.
  6. World Federation of Hemophilia. "What is hemophilia?" World Federation of Hemophilia website. http://www.wfh.org/en/page.aspx?pid=646 . Accessed June 23, 2017. 
  7. National Hemophilia Foundation. "Hemophilia A." National Hemophilia Foundation website. https://www.hemophilia.org/Bleeding-Disorders/Types-of-Bleeding-Disorders/Hemophilia-A .  Accessed June 23, 2017.
  8. World Federation of Hemophilia. "Who is at risk of developing inhibitors?" World Federation of Hemophilia website. http://www.wfh.org/en/page.aspx?pid=653 . Accessed June 23, 2017.
  9. World Federation of Hemophilia. "What are inhibitors?" World Federation of Hemophilia website. http://www.wfh.org/en/page.aspx?pid=651 . Accessed June 23, 2017.
  10. Centers for Disease Control and Prevention. "Hemophilia." Centers for Disease Control and Prevention website. http://www.cdc.gov/ncbddd/hemophilia/facts.html . Accessed June 29, 2017.

NOTES TO EDITORS

For further information please contact:

Investor Relations   
Ian Karp ikarp@shire.com +1 781 482 9018
Robert Coates rcoates@shire.com +44 1256 894874
 

Media
  
Molly Poarchmolly.poarch@shire.com+1 312 965 3413

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.

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, 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 may decrease its business flexibility and increase borrowing costs; 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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The issuer of this announcement warrants that they are solely responsible for the content, accuracy and originality of the information contained therein.

Source: Shire plc via GlobeNewswire
HUG#2118434
GlobeNewswire
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Last updated on: 07/07/2017

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