Shire Receives FDA Fast Track Designation for Recombinant ADAMTS13 (SHP655) for Treatment of Hereditary Thrombotic Thrombocytopenic Purpura

LEXINGTON, Massachusetts, March 22, 2017 /PRNewswire/ --

Shire plc (LSE: SHP, NASDAQ: SHPG) today announced that the United States Food and Drug Administration (FDA) has granted Fast Track designation for recombinant ADAMTS13 (SHP655 - historically known as BAX930) for treatment of acute episodes of hereditary thrombotic thrombocytopenic purpura (hTTP) in patients with a constitutional deficiency of the von Willebrand factor-cleaving (VWF) protease ADAMTS13. Hereditary thrombotic thrombocytopenic purpura is a life-threatening congenital disease caused by a deficiency in the enzyme ADAMTS13 which can cause clotting in the microvasculature with associated organ morbidities.^[1],[[4]]

"As the leader in rare disease, Shire is committed to providing an innovative pipeline of world class therapeutics to the patients that need them most," said Philip J. Vickers, Ph.D., Head of R&D, Shire. "Today's confirmation from FDA that SHP655 for hereditary thrombotic thrombocytopenic purpura has been granted Fast Track designation reaffirms the significant unmet need that exists for this patient population and provides hope of reducing morbidity in patients with hTTP."

FDA's Fast Track designation is supported by preclinical data and a Phase 1 study. The FDA's Fast Track process is designed to facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet medical need. However, it does not guarantee that the FDA will ultimately approve SHP655 or the timing of any such approval.

Shire will initiate its Phase 3 trial with SHP655 as a randomized, open-label, 2-period crossover study with a single arm continuation to evaluate the safety and efficacy of SHP655 in the treatment and prevention of acute TTP events in patients with severe hereditary ADAMTS13 deficiency.^[2] This global study will be conducted in the U.S., Europe, and Japan.^[3]

Additional information on the SHP655 Phase 1 study can be found on clinicaltrials.gov: https://clinicaltrials.gov/ct2/show/NCT02216084?term=BAX930&rank=1

The Phase 1 data included results from 15 patients with severe hTTP who completed the multicenter study. Each patient received a single dose of SHP655 in one of three dosing cohorts. The activity PK parameters, including terminal half-life, were comparable to those estimated from fresh frozen plasma (FFP) studies and demonstrated dose proportionality with respect to Cmax and AUC.^[[4]] No serious adverse events were reported. In the highest dosing cohort, three subjects reported three possibly related adverse events, nausea, flatulence and decreased VWF antigen and VWF activity; all of these reported adverse events resolved without medication. Immunogenicity tests performed at screening, pre-dose and upon study completion, were negative in all subjects.^[4]

About Hereditary Thrombotic Thrombocytopenic Purpura (hTTP)  

Hereditary Thrombotic Thrombocytopenic Purpura (hTTP) is a life-threatening congenital disease caused by a deficiency in the enzyme ADAMTS13. This deficiency can cause clotting in the microvasculature with associated organ morbidities.^[[1]],[[4]] Mortality is high if untreated. Currently, between 3,000 to 4,000 patients worldwide have hTTP^[5], and there are no approved treatment options although various other treatments are used off label and have a range of severe complications for patients.^[6] If approved, SHP655 (historically known as BAX 930) would be the world's first recombinant ADAMTS13 enzyme replacement therapy.

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

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, 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 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, including expected operating efficiencies, cost savings, revenue enhancements, synergies or other benefits at the time anticipated or at all with respect to Shire's acquisition of 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 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.

1. Furlan M, Lämmle B. Aetiology and pathogenesis of thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome: the role of von Willebrand factor-cleaving protease. Best Pract.Res.Clin.Haematol. 2001;14:437-454.

2. Clinical Study Protocol; A phase 3, randomized, controlled study of prophylactic and on-demand treatment of hTTP with BAX 930 (rADAMTS13), February 2017; 1-104.

3. Clinical Development Plan (SHP655); BAX 930/ rADAMTS13 Hereditary Thrombotic Thrombocytopenic Purpura. July 2015; 1-4.

4. Full Clinical Study Report 281101. BAX930 (rADAMTS13). June 2016; 1-238.

5. Mansouri Taleghani M. et al. Hereditary thrombotic thrombo -cytopenic purpura and the hereditary TTP registry. Schattauer 2013; 1-6.

6. Pandey S, Vyas G. Adverse effects of plasma transfusion; TRANSFUSION 2012;52:65S-79S

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SOURCE Shire plc