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, May 18, 2017 /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 α4β7 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 α4β7 + 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. 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 

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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• 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;
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• 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;
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• 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.

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