Introduction
SBS-IF is a severe organ failure condition with life-long PS dependence. Glucagon-like peptide-2 (GLP-2) stimulates intestinal adaptation resulting in increased absorptive capacity of nutrients and fluids. Apraglutide (APRA) is a novel long-acting synthetic GLP-2 analog in development for SBS-IF.
Aims & Methods
We performed a pre-defined interim analysis of a phase 2 study in SBS-IF-CiC to investigate the safety and efficacy of 4W APRA treatment based on metabolic balance studies (MBS). STARS Nutrition is a 52W phase 2 study in adult patients with SBS-IF-CiC receiving once-weekly subcutaneous APRA injections. Metabolic balance studies were performed at baseline and 4w with stable PS, followed by a 48w PS adjustment period. During MBS, fluid intake was kept constant (individual predefined drinking menu). Duplicates of meals and fluids (wet weight intake), urine and feces (fecal wet weight output) were collected. Safety was the primary endpoint. Secondary endpoints included changes in fecal wet weight output, urinary output, wet weight and energy absorption. Data are presented as mean (95% CI). P-values <0.05 were considered significant (Wilcoxon matched-pairs signed rank test).
Results
Nine patients were included and comprise the full study population. APRA was well tolerated (no dose discontinuation or interruption). Fecal wet weight output decreased significantly by 253 (-437 – -68) g/day (p=0.012). Relative wet weight absorption increased by 9 (1 – 18) % (p=0.039). There was a numeric increase in urinary output (p=0.129). No significant changes in energy absorption were observed.
Conclusion
These initial short-term results of APRA in SBS-IF-CiC support safety and efficacy in increasing relative but not absolute wet weight absorption. One-year treatment outcomes are awaited to assess the full effect on wet weight, energy, and macronutrient absorption.
Disclosure
FJ has received grants/research support/honoraria or consultation fees from Baxter, Fresenius Kabi, Nestlé Health Sciences, BBraun, Theradial, Mayoli, Biocodex, mobile 3econsulting, NPS Pharmaceuticals, Shire, Takeda, Therachon, VectivBio and Zealand Pharma.
PBJ has received grants/research support/honoraria or consultation fees from Albumedix A/S, ArTara Therapeutics, Bainan Biotech, Baxter, Coloplast, Ferring, Fresenius Kabi, GLyPharma, Naia Pharma, NPS Pharmaceuticals, Shire, Takeda, The Novo Nordisk Foundation, Therachon, VectivBio and Zealand Pharma.
TV has served on the speaker bureau for Fresenius Kabi, Remedus, Takeda, and VectivBio. TV has provided clinical advice to Baxter, Shire, Takeda, VectivBio, Zealand Pharma. TV has received research grants from Takeda and VectivBio.
This research was supported by VectivBio. FB, CL and OK are employees of VectivBio.