Key takeaways:
- At 1 year, apraglutide reduced parenteral support volume by 52% in patients with short bowel syndrome with intestinal failure and colon-in-continuity.
- The treatment had an acceptable safety profile.
Treatment with apraglutide resulted in a 52% reduction in weekly parenteral support volume at 1 year among nine patients with short bowel syndrome with intestinal failure and colon-in-continuity, according to data presented at UEG week.
“Since the last decade, disease-modifying treatments for patients with [short bowel syndrome with intestinal failure (SBS-IF)] have been introduced, and these are analogs of glucagon-like peptide-2, or GLP-2,” Astrid Verbiest, a PhD student at the University of Leuven Translational Research Center for Gastrointestinal Disorders, said during her presentation. “These GLP-2 analogs are hypothesized to boost the intestinal adaptation. Teduglutide is the first developed and marketed GLP-2 analog and is a short-acting GLP-2 analog.”
She continued, “From the clinical studies of teduglutide we have seen limited efficacy in patients with SBS-IF [and colon-in-continuity (CiC)]; however, real-world data now suggest that patients with SBS with remaining colon-in-continuity could benefit from treatment with GLP-2 analogs. Apraglutide is an investigational long-acting GLP-2 analog that is currently in development for SBS-IF.”
In the multicenter, open-label, phase 2 STARS Nutrition trial, Verbiest and colleagues assessed the safety and efficacy of apraglutide in reducing parenteral support (PS) needs at 52 weeks in patients with SBS-IF-CiC. They enrolled nine adults (mean age, 46.8 years; 78% women), who were given once-weekly subcutaneous injections of 5 mg apraglutide and evaluated at baseline and weeks 4 and 48.
Verbiest noted that within the first 4 weeks of treatment, researchers could not reduce PS; however, there was a 48-week PS adjustment after this time.
“During this period, patients had to perform a 48-hour urine collection every month while adhering to their predefined individual drinking menu,” she said. “If we could see an increase of at least 10% in their mean daily urinary output, we could reduce parenteral support.”
Participants had an average small bowel length of 19 cm, with 79% of the colon still in continuity, and averaged 9.9 liters of PS per week, distributed over 5 days, with an energy content of around 8,000 kcal.
The study’s primary endpoint was safety, and secondary endpoints included changes in PS weekly volume, energy content and days off; and proportion of clinical responders (PS reduction of 20%) and patients who achieved an additional 1 day or more off PS per week.
According to Verbiest, all nine patients experienced adverse events during the study, with a total of 127 events, the most common of which were nasopharyngitis, vomiting, diarrhea and injection site reaction. Three patients experienced serious adverse events and one, who developed obstructive cholangitis and interrupted dosing for 1 week, was treatment-related.
After 24 weeks of treatment, weekly PS volume significantly dropped by 40%, which was maintained with a 52% reduction at 1 year; a similar trend was reported for weekly PS energy. Participants’ body weight stabilized over the course of the study.
Further, after 8 weeks of treatment with apraglutide, three patients were considered clinical responders, which improved to seven patients at week 24. At 1 year, all nine patients were clinical responders, Verbiest noted, and seven patients could achieve at least 1 day off PS.
“What is more interesting to see is that on average at baseline, patients were on 5 days of parenteral support per week and after 1 year of treatment with apraglutide, the patients could gain 2 days off parenteral support,” she said.
Additionally, two patients achieved enteral autonomy, Verbiest continued, “meaning that they could stop their parenteral support infusions completely after 1 year of treatment.”