Clinical Trials

Date: 2017-05-18

Type of information: Publication of results in a medical journal

phase: 2

Announcement: publication of results in The Lancet

Company: Shire (UK - USA)

Product: SHP647 (PF-00547659)

Action mechanism:

monoclonal antibody. SHP647/PF-00547659 is a fully-human monoclonal antibody that is designed to directly target a gastrointestinal endothelial adhesion molecule known as mucosal addressin cell adhesion molecule 1 (MAdCAM-1), that binds to the alpha4beta7 integrin on lymphocytes. The interaction between endothelial MAdCAM-1 and ?4?7 integrin has been implicated in the pathogenesis of ulcerative colitis.3 SHP647 directly targets MAdCAM-1, thereby blocking tissue homing of activated ?4?7 + leukocytes.
Shire licensed the global rights to all indications for PF-00547659 (SHP647) from Pfizer in June 2016.

Disease: ulcerative colitis

Therapeutic area: Autoimmune diseases - Inflammatory diseases - Digestive diseases

Country: Croatia, Czech Republic, Norway, Sweden, UK

Trial details:

The 12-week, multicenter, double blind, placebo-controlled, parallel-group study (TURANDOT 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 ulcerative colitis. (NCT01620255)

Latest news:

• On May 18, 2017, Shire announced publication in the May 17, 2017 issue of The Lancet the results from a Phase 2 study 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. In the TURANDOT study, SHP647 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 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 ulcerative colitis.