Apraglutide

Safety Summary

Across the Phase 1/2 and Phase 2 SBS studies, treatment-related adverse events were usually mild to moderate and were dominated by GI/stoma effects and fluid-balance effects, including decreased stoma output, stoma complications, nausea, flatulence, polyuria, edema, abdominal pain, vomiting, and mild injection-site reactions (PMID 35233802; PMID 34287970; PMID 39461299). No treatment-related serious adverse events were reported in the randomized 4-week Phase 2 crossover trial PMID 34287970. One treatment-related SAE of abdominal pain was reported in the open-label Phase 1/2 study PMID 35233802. In the 52-week CiC study, 127 AEs were reported, mostly mild to moderate; one severe treatment-related SAE of acute obstructive cholangitis occurred in a patient with pre-existing asymptomatic cholecystolithiasis, requiring ERCP and cholecystectomy PMID 39461299. The full text of the CiC study notes that GLP-2 has been linked to gallbladder hypomotility contributing to bile stasis, and that liver function test monitoring is warranted during GLP-2 analog therapy PMID 39461299. A network meta-analysis found no significant safety difference between apraglutide and control groups; catheter-related bloodstream infection was the most common AE across GLP-2 analogs PMID 38663565. In Phase 1 studies, apraglutide was generally well tolerated with no serious adverse events or immunogenicity observed.