Shire Pharmaceuticals Group Plc

The Lancet Publishes Phase 2 Results from Shire's Investigational Anti-MAdCAM Antibody Showing Significantly Increased Remission Rates in Patients with Moderate-to-Severe Ulcerative Colitis

Dublin (ots/PRNewswire) -

- Study met primary endpoint demonstrating significantly greater 
  remission rates in patients receiving anti-MAdCAM antibody (SHP647)
  compared to placebo in three of four tested dose groups 
- First study to investigate the potential role of anti-MAdCAM 
  antibody in the management of ulcerative colitis (UC) 
- SHP647 specifically targets a gastrointestinal (GI) endothelial 
  adhesion molecule known as mucosal addressin cell adhesion molecule
  1 (MAdCAM-1)  

Shire plc (LSE: SHP, NASDAQ: SHPG), the global leader in rare and specialty diseases, today announced publication in the May 17, 2017 issue of The Lancet the results from a Phase 2 study (NCT01620255) investigating PF-00547659 (now called SHP647), an anti-mucosal addressin cell adhesion molecule 1 (MAdCAM-1) antibody, investigated in the treatment of moderate-to-severe ulcerative colitis in adults. Ulcerative colitis is a chronic, relapsing and remitting inflammatory disorder of the gastrointestinal tract that mainly affects the colon.[1] It is not uncommon for patients with ulcerative colitis to fail to respond to, or lose response to, available therapies.[2],[3] Therefore, there is a need to develop new therapies.[3]

In this Phase 2 study, called TURANDOT, SHP647, the first anti-MAdCAM antibody in clinical development, met its primary endpoint demonstrating significantly greater remission rates in patients receiving anti-MAdCAM antibody compared to placebo in three of four tested dose groups. Shire continues to work toward the initiation of a pivotal Phase 3 trial for SHP647 in the second half of 2017. The Company licensed the global rights to all indications for PF-00547659 (SHP647) from Pfizer Inc. (NYSE: PFE) in June 2016, adding to Shire's established and leading gastrointestinal (GI) portfolio.

The interaction between endothelial MAdCAM-1 and ?4?7 integrin has been implicated in the pathogenesis of ulcerative colitis.[3] SHP647 is a fully human monoclonal antibody that directly targets MAdCAM-1, thereby blocking tissue homing of activated ?4?7 + leukocytes.[4]

"The TURANDOT trial is the first study to investigate a new biologic, an anti-MAdCAM antibody, as a potential treatment for ulcerative colitis, a chronic intestinal disease with high unmet need," said Prof. Séverine Vermeire, MD, Department of Gastroenterology, University Hospital Leuven, Belgium and TURANDOT lead investigator. "These statistically significant results demonstrate the role that cell adhesion plays in ulcerative colitis and suggest that inhibition of cell adhesion mediated by MAdCAM may result in a potential treatment for patients suffering with this disease."

"For patients with ulcerative colitis, there is a critical need for new treatment options," said Philip Vickers, Ph.D, Global Head of Research & Development at Shire. "In line with Shire's commitment to researching and developing therapeutic advances for patients with GI conditions, we are encouraged by the statistically significant results of the TURANDOT trial and the potential for our anti-MAdCAM antibody to become an important therapeutic option for patients with ulcerative colitis."

About TURANDOT

The 12-week, multicenter, double blind, placebo-controlled, parallel-group study enrolled 357 patients with ulcerative colitis, who failed at least one previous treatment, who were randomized to receive SHP647 across four different dosing groups of 7.5 mg, 22.5 mg, 75 mg, and 225 mg or placebo. The study met the primary endpoint, which was the proportion of patients achieving disease remission at week 12 compared to placebo. Results showed that remission rates at week 12 were highest in patients receiving 22.5 mg (12/72, 16.7%) and 75 mg (11/71, 15.5%) of SHP647 and were significantly greater than placebo in three of the four SHP647 treatment groups. The study also met its secondary endpoints at week 12, which included the proportion of patients with a clinical response, and the proportion of patients with mucosal healing in the treatment groups compared to placebo. SHP647 appeared to be well tolerated in this patient population. As this trial was only 12 weeks in duration, these safety data should be interpreted with some degree of caution, a larger patient population treated for a longer period will be needed to fully assess the safety of SHP647 in patients with UC.[5] See additional safety data below.

The complete publication can be found at The Lancet (http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)30930-3/fulltext?elsca1=tlxpr). The study results were previously presented at Digestive Disease Week 2015.[6] Shire continues to work toward the initiation of a pivotal Phase 3 trial for SHP647 in Q3 2017.

TURANDOT Safety Data

The frequencies of subjects with permanent or temporary discontinuations due to treatment-emergent adverse events (TEAEs) were low (<5%). Overall, the frequencies of serious adverse events (SAEs) were low (5.9% of the total population). One (1) death (due to adenocarcinoma of the colon) occurred during the study in the SHP647 7.5 mg group, which was considered by the data monitoring committee as unlikely to be associated with the study drug. A larger patient population treated for a longer period will be needed to fully assess the safety of SHP647 in patients with UC.

About Ulcerative Colitis

Ulcerative colitis is a chronic, idiopathic, relapsing and remitting inflammatory disorder of the gastrointestinal tract that mainly affects the colon.[1] Symptoms can be debilitating and include frequent recurring diarrhea, rectal bleeding, fever, and abdominal pain.[7]

Ulcerative colitis is a cause of significant morbidity globally, with incidence and prevalence continuing to increase over time.[8] The disease can affect people of any age; however, the peak age of onset is 30-40 years.[9]

References

1. Ford AC, et al. BMJ. 2013;346:f432
2. Ghosh S, et al. Ther Adv Gastroenterol. 2010;3:239-258
3. Allocca M, et al. Expert Rev Clin Immunol. 2014;10:885-95
4. Pullen N, et al. Br J Pharmacol. 2009;157:281-93
5. Vermeire S, et al. Lancet. 2017 
http://dx.doi.org/10.1016/S0140-6736(17)30930-3
6. Reinisch W, et al. Gastroenterology. 2015;148:S1193
7. Ordás I, et al. Lancet. 2012;380:1606-19
8. Molodecky NA, et al. Gastroenterology. 2012;142:46-54
9. Cosnes J, et al. Gastroenterology. 2011;140:1785-94 

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;
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  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
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  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 
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  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;
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  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.

Contact:

please contact:
Investor Relations
Ian Karp
ikarp@shire.com
+1-781-482-9018

Robert Coates
rcoates@shire.com
+44(0)1256-894874

Media
Lisa Adler
lisa.adler@shire.com
+1-617-588-8607

Debbi Ford
debbi.ford@shire.com
+1-617-949-9083



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