Shire Receives FDA Breakthrough Therapy Designation for SHP621 and SHP625, Investigational Products for Rare Gastrointestinal Conditions

LEXINGTON, Massachusetts, June 13, 2016 /PRNewswire/ --

Shire plc (LSE: SHP, NASDAQ: SHPG) today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for two investigational products for rare diseases: SHP621 (budesonide oral suspension, or BOS) for eosinophilic esophagitis (EoE), and SHP625 (maralixibat) for progressive familial intrahepatic cholestasis type 2 (PFIC2).

"Receiving Breakthrough Therapy Designation on two pipeline products this past week reflects the potential of our strong and innovative pipeline of more than 60 programs," said Flemming Ornskov, M.D., MPH, and CEO, Shire. "Shire is committed to bringing innovation to the rare and specialty areas we focus on. We persevere to see compounds through the many stages of development through their challenges and successes, and always keep patients with unmet needs top of mind."

EoE is a serious, chronic and rare disease that stems from an elevated number of eosinophils, a type of white blood cell, that infiltrate the walls of the esophagus. EoE is characterized by an inflammation of the esophagus that may lead to difficulty swallowing (dysphagia). The diagnosed prevalence of EoE ranges from approximately 15-55 cases per 100,000 persons, with high-end estimates reported by studies in Western regions.

PFIC refers to a group of autosomal-recessive liver disorders of childhood that disrupt bile formation and present with cholestasis. The symptoms of PFIC include severe itching of the skin (pruritus), and jaundice. PFIC is estimated to affect 1 in 50,000 to 1 in 100,000 births. PFIC2 is the most common type of PFIC, accounting for around half of cases.

According to the FDA, Breakthrough Therapy Designation is granted to a therapy that is intended to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on one or more clinically significant endpoints over current standard of care. Under the designation, the FDA provides intensive guidance, organizational commitment involving senior managers, and eligibility for rolling and priority review of the application; this process helps ensure patients have access to therapies as soon as possible, pending approval. Breakthrough Therapy Designation does not guarantee that FDA will ultimately approve BOS for EoE or maralixibat for PFIC2, and the timing of any such approval is uncertain.

"On behalf of patients in the United States with EoE and PFIC2, we are so pleased that the FDA has granted Breakthrough Therapy Designation to BOS and maralixibat," said Philip J. Vickers, Ph.D., Head of R&D, Shire. "We look forward to working with the agency to continue their development and, pending FDA approval, deliver these therapeutic options to the patients who need them most."

About SHP621 BOS  

BOS is a novel, topically active, oral viscous formulation of budesonide. BOS is formulated specifically for EoE; in an open-label clinical trial, orally administered viscous budesonide was more effective than nebulized or swallowed budesonide for improving esophageal eosinophil counts and endoscopic findings in adults with a new diagnosis of EoE.

Breakthrough Therapy Designation was granted based on the results from a Phase 2 trial in adolescents and adults (ages 11-40) with EoE. The co-primary endpoints were met and, compared with placebo, 12 weeks of budesonide oral suspension treatment significantly reduced both dysphagia symptoms and achieved higher proportion of subjects with histologic response (< 6 eos/hpf for all biopsies). There were no differences in cortisol levels, growth velocity (for age <18), or adverse events between the BOS and placebo groups. One subject on BOS developed esophageal candidiasis.

BOS has received orphan drug designation from the FDA. SHP621 BOS is currently in Phase 3; the clinical trial program investigating BOS in adolescents and adults ages 11-55 years with EoE was initiated in late 2015.

About EOE 

EoE is a chronic rare disease that has been increasingly recognized over the past decade. Although the exact cause of EoE is unknown, it is believed to be triggered by a variety of stimuli including certain foods and environmental allergens. In severe cases, it can lead to strictures causing food impaction (food getting stuck in the esophagus), and in children it can lead to poor growth or weight loss due to feeding difficulties. Current management of EoE includes a trial of proton pump inhibitors and, if not effective, the elimination of certain food from patient diets, and different steroid formulations. Currently, there are no therapeutic options specifically indicated for the treatment of EoE.

About SHP625 Maralixibat  

Maralixibat (LUM001) is being evaluated in several rare cholestatic liver diseases for both pediatric and adult populations. Preclinical models suggest that maralixibat is a potent, selective inhibitor of the apical sodium-dependent bile acid transporter (ASBT). ASBT inhibitors are designed to block bile acid reabsorption in the ileum and increases fecal bile acid excretion. Shire is developing maralixibat as an oral solution formulation for pediatric indications. Maralixibat was granted orphan designation by both the FDA and the European Medicines Agency (EMA). Maralixibat is currently in Phase 2 trials for PFIC.

The Breakthrough Therapy Designation for maralixibat in PFIC2 was supported by the interim results of Shire's Phase 2 single-arm, open-label study LUM001-501 (INDIGO) in pediatric patients with PFIC.

While the interim results of INDIGO demonstrated no statistically significant reduction in mean serum bile levels from baseline across the study population as a whole, a subpopulation of patients with PFIC2 showed decreases from baseline in serum bile acids, marked reductions in pruritus, and normalization of liver parameters in those patients with liver enzymes that were elevated at baseline.

Twelve of the 33 patients enrolled (36.4%) experienced a serious treatment-emergent adverse event, of whom 4 patients (12.1%) experienced a total of 5 serious treatment-emergent adverse events which were assessed by investigator as causally related to treatment (abdominal pain upper, diarrhea, cholangitis, blood bilirubin increased, and international normalized ratio increased).

About PFIC 

Three types of PFIC have been identified and related to mutations in hepatocellular transport system genes involved in bile formation. PFIC2 usually appears in the first months of life. Treatment options for PFIC are generally focused on surgical treatment, such as partial external biliary diversion (PEBD) or liver transplantation. PFIC is the cause of 10-15% of liver transplant indications in children. Currently, there are no therapeutic options specifically indicated for the treatment of PFIC.

About Shire 

Shire is the leading global biotechnology company focused on serving people with rare diseases and other highly specialized conditions. We have best-in-class products available in more than 100 countries across core therapeutic areas including Hematology, Immunology, Neuroscience, Lysosomal Storage Disorders, Gastrointestinal / Internal Medicine / Endocrine and Hereditary Angioedema; a growing franchise in Oncology; and an emerging, innovative pipeline in Ophthalmics.

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 the financial and strategic benefits of the combination with Baxalta, our 20x20 ambition that targets $20 billion in combined product sales by 2020, as well as other targets for future financial results, capital structure, performance and sustainability of the combined company, the combined company's 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 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.

FOR FURTHER INFORMATION PLEASE CONTACT:

Investor Relations
Sarah Elton-Farr, seltonfarr@shire.com, +44(0)1256-894157
Robert Coates, rcoates@shire.com , +44(0)1256-894874
Ian Karp, ikarp@shire.com, +1-781-482-9018

Media
Gwen Fisher, gfisher@shire.com , +1-781-482-9649
Clotilde Houzé, chouze@shire.com , +1-781-266-3567