The condition, also known as SBS, occurs when part of the small intestine is missing. Its hallmark is patients being unable to absorb enough nutrients into their body.
SBS is a life-threatening chronic disease. Those with severe cases can become dependent on daily parenteral support, or being fed intravenously rather than through their digestive system.
Since parenteral support requires tubes and pumps, drugs that are able to reduce the need for IV feeding can improve patients’ quality of life.
Glepaglutide mimics glucagon like peptide 2 (GLP-2), a hormone that the small intestine produces. Because GLP-2 promotes intestinal growth and regeneration, scientists are trying to develop therapies for gastrointestinal diseases around it.
Researchers decided to evaluate the effectiveness, safety and tolerability of three doses of glepaglutide in adults with SBS. The highest dose was 10 times larger than the middle dose and 100 times larger than the smallest.
Sixteen patients completed the trial (NCT02690025). Each received two doses. The first one was followed by a four-week break and then another dose.
The study’s primary objective was to see whether glepaglutide would improve patients’ intestinal absorption, or the small intestine’s ability to absorb nutrients from food.
One measure the researchers used to determine intestinal absorption was fecal weight, with the higher the weight meaning the less absorption. The largest glepaglutide dose reduced fecal weight by 30 percent, and the middle dose by 23 percent.
Other energy-uptake measures the team used were alterations in patients’ urine output and in their absorption of electrolytes and macronutrients, or nutrients the body needs in large amounts. The two largest doses of glepaglutide increased those measures, the researchers said.
Glepaglutide was also safe, and patients tolerated it well. Most of the adverse effects were mild to moderate. They included nausea, vomiting, abdominal pain, decreased appetite, and reactions at the sites where glepaglutide was injected.
“This is the most comprehensive Phase 2 trial conducted to date in patients with SBS,” Dr. Palle Bekker Jeppesen, the trial’s principal investigator, said in a press release.
“SBS is a severe chronic condition where patients need better treatments to improve intestinal absorption,” added Bekker, a gastroenterologist at the University of Copenhagen’s Rigshospitalet. “The results of this Phase 2 trial suggest the potential of glepaglutide to provide increases in both energy, fluid and electrolyte absorption.”
“We are very pleased with these Phase 2 findings,” said Adam Steensberg, an executive vice president at Zealand. “Zealand plans to advance glepaglutide through further clinical trials as quickly as possible. We now look forward to continuing our dialogue with U.S. and EU regulatory authorities, with the aim of taking glepaglutide into Phase 3 clinical development in 2018.”