S2211 Phase 3, Double-Blind, Randomized STARS Trial of Apraglutide Once-Weekly in Patients with Short Bowel Syndrome and Intestinal Failure (SBS-IF): Subgroup Analyses by Baseline Demographics and SBS Disease Characteristics

Introduction:
Patients with short bowel syndrome (SBS) and intestinal failure depend on parenteral support (PS) to meet nutritional and/or fluid requirements, based on remnant bowel anatomy. Apraglutide (APRA), a long-acting glucagon-like peptide-2 (GLP-2) analog administered subcutaneously (SC) once-weekly, stimulates intestinal adaptation and reduce PS requirements, as shown in the pivotal STARS trial. Here we present subgroup analyses from this trial evaluating the treatment effect of APRA vs placebo (PBO) by baseline (BL) demographic and SBS disease-specific characteristics.

Methods:
STARS was a global, Phase 3, double-blind, PBO-controlled trial (NCT04627025) evaluating efficacy and safety of APRA (5 mg if patient ≥50 kg, 2.5 mg if patient< 50kg) or matching PBO (randomization 2:1), stratified by residual intestinal anatomy (stoma or colon-in-continuity). The primary endpoint was relative change from BL in actual PS weekly volume at Week (wk) 24 in the overall population. Reduction of additional ≥1 day/wk off PS from BL was a key secondary endpoint. This subgroup analysis examined the primary endpoint by demographics: gender, age (< 65 and ≥65 years old), body weight (< 50 and ≥50 years old), region (European Union, United States, or rest of the world), race (Asian, white, or other), ethnicity (Hispanic/Latino or not); and SBS disease characteristics: PS volume (< 12 and ≥12 L), length of remnant small intestine (< 80 cm and ≥80 cm), and time from SBS diagnosis (< 65.7 and ≥65.7 months) at BL. Analyses used a mixed effect model for repeated measures (MMRM).

Results:
The primary endpoint was met at wk 24 (n=163; overall population), with a significantly larger reduction in weekly PS volume from BL with APRA vs PBO (-25.5% vs -12.5%, P =0.001). These results have been presented previously. Subgroup analyses showed consistent treatment effect for APRA vs PBO across all subgroups in the overall population (Figure 1). A similar magnitude of effect was observed regardless of body weight, with differences of -16.0% (P =0.188) and -14.1% (P =0.001) in patients weighing < 50 kg (reflects the 2.5 mg dose) and ≥50 kg (reflects the 5 mg dose). Similar magnitude of effect was also seen regardless of whether PS volume at BL was < 12L or ≥12L (-13.6% [P =0.054] and -13.4% [P =0.002]).

Conclusion:
In the overall population of the STARS trial, subgroup analyses of the primary endpoint by BL demographics and SBS disease characteristics showed consistent treatment effect of APRA.