Targeted therapy of short-bowel syndrome with teduglutide: the new kid on the block

Figures & data

Table 1 Clinical trials on teduglutide

Clinical study	Study objective	Subjects (n)	Study duration	Teduglutide dose	Outcomes
Phase II study (open-label, multicenter, pilot)^Citation19	To evaluate the safety, tolerability, and effect of multidose treatment with teduglutide in PN-dependent SBS patients	16	3 weeks	0.03 mg/kg daily or 0.10 or 0.15 mg/kg daily or twice daily	Decrease in fecal wet weight (711±734 g/day, P=0.001) and fecal energy loss (808±1,453 kJ/day, P=0.040) Increase in absolute wet weight (743±477 g/day, P<0.001) Increase in relative wet weight (22%±16%, P<0.001) Increase in urine wet weight (555±485 g/d, P>0.001) Increase in sodium excretion (53±40 mmol/day, P>0.001) Increase in intestinal (biopsies) – villus height (38%±45%, P=0.030) – crypt depth (22%±18%, P=0.010) – mitotic index (115%±108%, P=0.010)
Phase III study (first randomized, multicenter, placebo-controlled trial)^Citation6	To evaluate the efficacy, tolerability, safety, and PK of teduglutide in PN-dependent SBS patients	83	24 weeks	0.05 mg/kg/day and 0.10 mg/kg/day	≥20% reduction of weekly PS-volume requirement was noted in 16 of 35 (46%) in low-dose (0.05 mg/kg/day) group when compared with placebo (P=0.007) and in 8 of 32 (25%) in high-dose (0.10 mg/kg/day) group (P=0.161) Secondary outcomes: Increase in lean body mass, total body bone mineral content, intestinal villus height, and plasma citrulline (biomarker of enterocyte mass) levels was noted in both dose groups versus placebo
Phase III study – STEPS (double-blind, multicenter RCT)^Citation7	Confirmatory RCT on safety, efficacy, tolerability, and PK of teduglutide in PN-dependent SBS patients	86	24 weeks	0.05 mg/kg/day	≥20% reduction in weekly PS volume at week 20 through week 24 was noted in 63% (27 of 43) in the teduglutide group versus 30% (13 of 43) in the placebo group (P=0.002) Secondary outcomes: Teduglutide group had – higher mean PS-volume reduction of 4.4±3.8 L/week (32%±19%) versus 2.3±2.7 L/week (21%±25%) reduction in the placebo group (P>0.001) – greater reduction in percentage of patients with ≥1 day in the weekly need for PS (21 of 39 [54%]) versus (9 of 39 [23%], P=0.005)
Phase III study (randomized, multicenter, double-blind, open-label “extension” study)^Citation20	To evaluate the long-term safety and efficacy in PN-dependent SBS patients who had already received the drug for 24 weeks in the first Phase III trial	52	52 weeks	0.05 mg/kg/day and 0.10 mg/kg/day	≥20% reduction in PS volume was noted in 68% in the 0.05 mg/kg/day teduglutide group and 52% in the 0.10 mg/kg/day group Reduction of ≥1 day(s)/week of PN dependence was noted in 68% in the 0.05 mg/kg/day group versus 37% in the 0.10 mg/kg/day group

Abbreviations: PN, parenteral nutrition; SBS, short-bowel syndrome; PK, pharmacokinetics; PS, parenteral support; RCT, randomized controlled trial; STEPS, Study of Teduglutide Effectiveness in Parenteral nutrition dependent Short bowel syndrome subjects.

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