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

  • 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)

DUBLIN, Ireland I May 18, 2017 I 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

  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

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.

SOURCE: Shire

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