Shire's SHP626 (Volixibat) Receives FDA Fast Track Designation for an Investigational Treatment for Adults Who Have Nonalcoholic Steatohepatitis (NASH) With Liver Fibrosis

LEXINGTON, Massachusetts, July 29, 2016 /PRNewswire/ --

Shire plc (LSE: SHP, NASDAQ: SHPG) today announced that the United States Food and Drug Administration (FDA) has granted Fast Track designation for SHP626 (volixibat) for an investigational treatment of adults who have nonalcoholic steatohepatitis (NASH) with liver fibrosis. Shire is developing SHP626 as a once daily, orally-administered inhibitor of the apical sodium dependent bile acid transporter (ASBT), a protein which is primarily responsible for recycling bile acids from the intestine to the liver. NASH is a serious, chronic liver disease for which there are currently no approved drugs.

"Shire's development plan for SHP626 is designed to address the unmet need in the treatment of adult patients who have NASH with liver fibrosis," said Philip J. Vickers, Ph.D., Head of R&D, Shire. "This Fast Track designation is further recognition of the critical need to develop new, effective therapeutic options for patients with this serious condition."

The FDA Fast Track Designation for SHP626 in NASH was supported by preclinical and Phase 1 studies. The FDA's Fast Track is a process 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 SHP626 for NASH or the timing of any such approval.

Shire will initiate its Phase 2 trial with SHP626 as a randomized, placebo-controlled, double-blind study to evaluate the safety, tolerability and efficacy of three doses of volixibat over 48-weeks in adult patients with NASH. The Phase 2 study will be conducted in the U.S., Canada and the United Kingdom.

Additional information on the SHP626 Phase 2 study can be found on clinicaltrials.gov:

https://clinicaltrials.gov/ct2/show/NCT02787304?term=volixibat&rank=1

SHP626 has been evaluated in preclinical and Phase 1 studies, in which the safety, tolerability and preliminary activity of SHP626 compared to placebo in healthy volunteers, as well as in overweight and obese volunteers, was assessed. The most common adverse events occurring in Phase 1 trials of SHP626 were gastrointestinal in nature, predominantly diarrhea. While this occurred in most patients, it was not considered serious. There was one serious adverse event reported that was considered related to SHP626, alanine aminotransferase elevation, that led to discontinuation of drug.

About Nonalcoholic Steatohepatitis (NASH) 

NASH is a type of nonalcoholic fatty liver disease (NAFLD), characterized by inflammation and the accumulation of fat in the liver, for which there are currently no approved drugs. It can be severe and lead to fibrosis, cirrhosis, liver failure and liver cancer. There is a steady rise in the prevalence of NASH in the U.S. and globally, and the disease is typically associated with obesity, type 2 diabetes, hypertension, high cholesterol and triglycerides. NASH is currently the second leading cause of liver transplantation in adults in the U.S., and is estimated to become the leading cause for liver transplantation if the current trajectory continues.

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:

• disruption from the acquisition and integration of Baxalta Incorporated ("Baxalta") may make it more difficult to conduct business as usual or maintain relationships with patients, physicians, employees or suppliers;
• the company may not achieve some or all of the anticipated benefits of Baxalta's spin-off from Baxter International, Inc. ("Baxter") and the acquisition may have an adverse impact on Baxalta's existing arrangements with Baxter, including those related to transition, manufacturing and supply services and tax matters;
• the failure to achieve the strategic objectives with respect to the acquisition of Baxalta may adversely affect the company's financial condition and results of operations;
• products and product candidates may not achieve commercial success;
• product sales from ADDERALL XR and INTUNIV are subject to generic competition;
• the failure to obtain and maintain reimbursement, or an adequate level of reimbursement, by third-party payers in a timely manner for the company's products may affect future revenues, financial condition and results of operations, particularly if there is pressure on pricing of products to treat rare diseases;
• supply chain or manufacturing disruptions may result in declines in revenue for affected products and commercial traction from competitors; regulatory actions associated with product approvals or changes to manufacturing sites, ingredients or manufacturing processes could lead to significant delays, an increase in operating costs, lost product sales, an interruption of research activities or the delay of new product launches;
• the successful development of products in various stages of research and development 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 the company's ability to sell or market products profitably, and fluctuations in buying or distribution patterns by such customers can adversely affect the company's revenues, financial condition or results of operations;
• investigations or enforcement action by regulatory authorities or law enforcement agencies relating to the company'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;
• adverse outcomes in legal matters, tax audits and other disputes, including the company'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;
• Shire is undergoing a corporate reorganization and was the subject of an unsuccessful acquisition proposal and the consequent uncertainty could adversely affect the company's ability to attract and/or retain the highly skilled personnel needed to meet its strategic objectives;
• failure to achieve the strategic objectives with respect to Shire's acquisition of NPS Pharmaceuticals Inc. or Dyax Corp. ("Dyax") may adversely affect the company's financial condition and results of operations;
• the company 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 the company's revenues, financial condition or results of operations;
• the company may be unable to retain and hire key personnel and/or maintain its relationships with customers, suppliers and other business partners;
• difficulties in integrating Dyax or Baxalta into Shire may lead to the company not being able to realize the expected operating efficiencies, cost savings, revenue enhancements, synergies or other benefits at the time anticipated or at all; and
• other risks and uncertainties detailed from time to time in Shire's, Dyax's or Baxalta's filings with the Securities and Exchange Commission, including those risks outlined in "ITEM 1A: Risk Factors" in Shire's and Baxalta's Annual Reports on Form 10-K for the year ended December 31, 2015.

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 republish revised forward-looking statements to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events.

S15059 07/2016

INTSP/EXA/GBU/16/001

For further information please contact: 

Investor Relations
Sarah Elton-Farr, seltonfarr@shire.com , +44-1256-894157
Ian Karp, ikarp@shire.com, +1-781-482-9018
Robert Coates, rcoates@shire.com, +44-1256-894874

Media
Gwen Fisher, gfisher@shire.com, +1-484-595-9836
Debbi Ford, debbi.ford@shire.com, +1-617-949-9083