Apraglutide: once weekly, one more trial to go

Apraglutide is a long-acting GLP-2 analogue designed for once weekly injection. It was developed by VectivBio, which Ironwood Pharmaceuticals agreed to buy in May 2023. Ironwood describes it as a once weekly, long-acting synthetic GLP-2 analogue for rare gastrointestinal diseases. Its lead use is short bowel syndrome with intestinal failure (SBS-IF). It is not approved anywhere.

The STARS trial

STARS was a global, double-blind, placebo-controlled phase 3 trial. Adults with SBS-IF were randomised 2:1 to once weekly apraglutide or placebo, split by anatomy: those with a stoma and those whose remaining colon is still connected (colon-in-continuity). The primary endpoint was the relative change in weekly parenteral support volume at week 24. Topline results came in February 2024; the full paper was published online in Clinical Gastroenterology and Hepatology in September 2026.

The pattern matters. The benefit was clear in people with a stoma. In people with a colon still in continuity, the 48 week results did not separate significantly from placebo. That is consistent with biology: an intact colon makes its own GLP-2 and absorbs fluid, so there is less to gain. The authors reported apraglutide as well tolerated.

The primary endpoint is a relative (percentage) change, while teduglutide's STEPS and glepaglutide's EASE-1 reported responders and absolute litres. That is one reason the three cannot be compared side by side.

Why once weekly matters

People with intestinal failure already spend several nights a week attached to an infusion. Teduglutide adds a daily injection, dosed by weight and mixed from powder. A once weekly injection removes six injections a week. That is the commercial case for apraglutide, and Ironwood's own description calls it the first GLP-2 analogue to show a statistically significant cut in weekly parenteral support with once weekly dosing. That is a company claim; the clinical value of fewer injections has not been tested against daily teduglutide in a trial.

The programme also includes smaller studies. STARS Nutrition, a phase 2 metabolic balance study in people with a colon in continuity, enrolled 10. A phase 1 study of apraglutide's effect on gastric emptying enrolled 42. Neither changes the efficacy picture, but both feed the safety file.

Why the FDA wants a second trial

Ironwood began a rolling new drug application in early 2025. On 14 April 2025 it announced that a pharmacokinetic analysis had shown the exposure and dose delivered in STARS were lower than planned, because of how the dose was prepared and administered. After talking with the FDA, the company said, it became clear a confirmatory phase 3 trial would be needed for approval. Ironwood said the STARS data would remain part of any future application.

Put plainly: the trial worked, but patients may not have received the dose the label would specify, so the FDA wants to see the intended dose tested.

STARS-2

Ironwood met the FDA in late 2025 to agree the design. In its May 2026 results release, it described STARS-2 as a 24 week, global, randomised, double-blind, placebo-controlled trial with the primary endpoint of relative change from baseline in actual weekly parenteral support volume, and said site initiations were planned for the second quarter of 2026. ClinicalTrials.gov lists STARS-2 as recruiting, with an estimated 124 participants receiving once weekly apraglutide or placebo. No STARS-2 results exist yet.

Patients from STARS continue in an open-label extension, STARS Extend, which the registry lists with 158 participants and the status active, not recruiting.

Graft-versus-host disease

Apraglutide has also been tested in steroid-refractory gastrointestinal acute graft-versus-host disease, a complication of stem cell transplant in which donor immune cells attack the gut. The phase 2 STARGAZE trial had safety as its primary objective. In March 2024 Ironwood reported that apraglutide was well tolerated through day 91 and that exploratory lower GI responses were maintained, without giving response rates in the release. The ClinicalTrials.gov record lists the trial as terminated, with 31 participants enrolled and the reason given as a company decision. Treat this as an exploratory safety study, not evidence of benefit.

Where it stands

For the other GLP-2 analogues, see teduglutide, the approved daily option, and glepaglutide, the twice weekly one recommended in the EU.

What to log

For anyone in a trial or on a GLP-2 analogue later, the useful record is the weekly injection, site, intravenous volumes, weight and labs on one timeline. Peptide AI's dose log, injection site rotation and bloodwork tracking cover that.