Teduglutide, A Novel Analog of Glucagon-like Peptide 2 (GLP-2), Is Effective and Well Tolerated in Reducing Parenteral Support (PS) Volume in Short Bowel Syndrome-Intestinal Failure (SBS-IF) Subjects: Results from a 24-week, Placebo-Controlled Phase 3 Trial: 247

Purpose: Teduglutide, a dipeptidyl peptidase-IV degradation-resistant analog of human GLP-2, repairs and restores functional and structural integrity of the intestinal mucosa, increasing villous height and crypt depth. The purpose of this study was to evaluate teduglutide 0.05 mg/kg/d given subcutaneously (SC) when compared with placebo on its ability to reduce the PS volume (IV fluids, nutrients, or both) in SBS-IF subjects dependent on PS. Methods: Eighty-six SBS-IF subjects, dependent on PS for ≥1 year, were enrolled in a randomized, double-blind, placebo-controlled, parallel-group, multinational, multi-center, 2-stage study. After an initial optimization/stabilization period of PS and urine volume, subjects were randomized to teduglutide 0.05 mg/kg/d SC or placebo for 24 weeks. A responder was defined as a subject who experienced a 20% to 100% reduction from baseline in weekly PS volume at weeks 20 and 24. The primary efficacy endpoint of the study compared the percentage of responders on teduglutide vs placebo. Results: Seventy-eight SBS-IF subjects completed the study (teduglutide 0.05 mg/kg/d, n=39; placebo, n=39). In intention-to-treat (ITT) population, 63% (27/43) of SBS-IF subjects on teduglutide 0.05 mg/kg/d were responders vs 30% (13/43) receiving placebo (p=0.002). Significant response was seen in the teduglutide subjects as early as week 8 and increased through week 24 compared with placebo in SBS-IF subjects. At week 24, teduglutide reduced mean weekly PS volume by 4.4 L/wk (12.9 L/wk at baseline), whereas PS volume reduction with placebo was 2.3 L/wk (13.2 L/wk at baseline; p≤0.001). Significantly more teduglutide-treated subjects were able to reduce the number of infusion days per week by 1 or more days than placebo (21/39 subjects, 54% vs 9/39 subjects, 23%; p=0.0047). Teduglutide was well tolerated; of the 8 discontinued, 3 of 4 in placebo group and 2 of 4 in teduglutide group were due to adverse events (AEs). AEs were found in 83% (35/42) treated with teduglutide vs 79% (34/43) in subjects treated with placebo. The most common AEs were abdominal pain, nausea, gastrointestinal stoma complications, and abdominal distension. Conclusion: Teduglutide 0.05 mg/kg/d SC, was effective and well tolerated in reducing weekly PS volume. Independence from PS, characterized by fewer days per week of PS infusion, was significantly greater with teduglutide. Disclosure: Dr. O'Keefe - Advisory Board Member: NPS Pharmaceuticals 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. Seidner - Grant/Research Support: NPS Pharmaceuticals, Consultant: Abbott Laboratories, Consultant: B. Braun Dr. Heinze - Employee: Nycomed GmBH Dr. Joelsson - Employee: NPS Pharmaceuticals.