EU panel backs glepaglutide for adults with short bowel syndrome

The European Medicines Agency’s human medicines committee has recommended authorization of glepaglutide, a peptide therapy intended to reduce the burden of intravenous support for adults with short bowel syndrome. The opinion was adopted September 17 and published September 18, moving Zealand Pharma’s proposed medicine, Zeydovio, closer to a European Commission decision.

The recommendation matters for patients whose remaining intestine cannot absorb enough fluid and nutrients. Reducing their dependence on parenteral support could ease a demanding part of daily disease management. As of September 20, however, EMA still listed the European Commission decision as pending; the committee recommendation does not itself authorize marketing.

A treatment aimed at intestinal absorption

Short bowel syndrome commonly follows surgical removal of a substantial portion of the intestine. Some patients require ongoing parenteral support—fluids or nutrition delivered intravenously—to meet their needs.

Glepaglutide is a long-acting analogue of glucagon-like peptide-2, or GLP-2. EMA describes its effects on intestinal tissue growth and function, including promotion of the intestinal lining. The recommended indication covers adults with short bowel syndrome who have stabilized after a period of intestinal adaptation following surgery.

For this population, the practical goal is to reduce the amount of support required and potentially the number of days spent receiving it. Those outcomes address treatment burden directly; they do not establish longer survival or a general benefit against aging.

What the randomized trial found

The pivotal EASE-1 study was an international, double-blind, placebo-controlled phase 3 trial involving 106 patients with short bowel syndrome and intestinal failure. Participants required parenteral support at least three days weekly and were assigned to two glepaglutide schedules or placebo for 24 weeks.

The primary endpoint was change in weekly parenteral-support volume. The twice-weekly treatment group recorded an average reduction of 5.13 liters per week, compared with 2.85 liters for placebo. The between-group difference was statistically significant.

A reduction of at least one support day per week occurred in 51.4% of that treatment group, versus 19.4% with placebo. Five patients in the twice-weekly group completely discontinued support, compared with none receiving placebo. Most treated participants therefore still required some support. The once-weekly group did not show statistically significant benefits over placebo on the primary or key secondary endpoints.

These are earlier findings, published online in December 2024 and in Gastroenterology’s April 2025 issue. The current development is the regulatory recommendation, rather than a newly reported trial result.

Safety and remaining questions

EMA lists common adverse effects including injection-site reactions, complications involving gastrointestinal stomas, abdominal pain, nausea, vomiting, and fluid retention or overload. Its opinion specifies specialist supervision for treatment initiation. A reduction in intravenous requirements must therefore be considered alongside treatment risks and ongoing monitoring needs.

The placebo comparison supports a treatment effect over 24 weeks, but the modest study size limits conclusions about uncommon harms. It also does not establish superiority to another active medicine or demonstrate that reduced support translates into fewer serious complications over many years.

Zealand says the regulatory package also included interim extension-study results and a mechanistic study examining intestinal absorption. The company expects results from the longer-term extension trials to be presented at scientific meetings in 2027; that planned presentation should not be mistaken for a new, fully available comparative dataset today.

The company also reports that the confirmatory phase 3 EASE-5 trial is recruiting to support a U.S. regulatory submission. For Europe, the next milestone is the Commission’s decision and, if authorization follows, publication of the detailed prescribing information. The evidence currently supports a potential reduction in support burden for a defined intestinal-failure population, with longer-term outcomes still requiring scrutiny.