Teduglutide (TED) for the Treatment of Short Bowel Syndrome-Intestinal Failure (SBS-IF) Subjects Yields Further Reductions in Parenteral Support (PS): An Interim Assessment of a 2-Year, Open-label, Phase 3 Trial (STEPS2)

Abstract

Purpose: TED, a dipeptidyl peptidase-IV degradation-resistant analog of human GLP-2, helps to restore functional and structural integrity of the intestinal mucosa. In a 24-week, placebo-controlled, phase 3 trial, significant mean PS volume reduction of 4.4 L/wk for TED vs 2.3 L/wk for placebo (PLA) was achieved in patients with SBS-IF (STEPS). STEPS2 is an openlabel, multi-center, multi-national, 2-year study that examines TED 0.05mg/kg/day for subjects who had participated in STEPS. The primary objective of this study is to collect long-term safety and tolerability data. In addition, PS volume changes from STEPS baseline continue to be monitored. Methods: 76 of the 78 subjects who completed STEPS enrolled in STEPS2. 37 subjects had received TED while 39 had received PLA. Baseline PS volume was 12.9 L/wk and 13.21 L/wk for the TED and PLA, respectively. Additionally, 12 subjects (baseline PS volume 13.3 L/wk) who completed optimization and stabilization in STEPS had direct rollover into STEPS2. These preliminary interim results of tolerability and presence of TED antibodies are based on subjects who have completed at least month 6 in STEPS2. Results: 12 subjects have discontinued from the extension trial, 9 for an adverse event (AE). The most commonly reported AEs are gastrointestinal (22%, consisting of abdominal pain, distension, nausea, vomiting), general disorder (13%, consisting of edema, injection site-related events such as swelling and redness, pyrexia), and infection (12%, consisting of catheter related infections, urinary tract infection, viral infection). The type frequency and intensity of AEs was not different when compared to results of STEPS. Reductions in PS volume continue to be observed in study participants. 3 subjects (2 TED/TED and 1 PLA/TED, STEPS/STEPS2) have been completely weaned off PS after 6.5, 8, and 9 months of exposure to TED, respectively. To date, no neutralizing antibodies to TED have been observed. Conclusion: This preliminary 6 month assessment of STEPS2 shows continued TED treatment is well tolerated in the majority of subjects. No unexpected safety signal regarding AEs has been observed to date. Further reduction in PS volume was observed in 3 subjects who were completely weaned off of PS. Disclosure: Dr. Schwartz - No financial relationship to disclose Dr. Seidner - Grant/Research Support: NPS Pharmaceuticals, Consultant: Abbott Laboratories, Consultant: B. Braun Dr. Jeppesen - Consultant: NPS Pharmaceuticals, Consultant: Nycomed GmbH Dr. Pertkiewicz - Consultant: NPS Pharmaceuticals, Member of Advisory Board: Nutricia Scientific Foundation, Lectures at Teaching Workshops Dr. Youssef - Employee: NPS Pharmaceuticals Dr. Heinze - Employee: Nycomed GmBH.Table 1: Summary of subjects weaned off of PS STEPS2