Bottom line
Apraglutide (FE 203799) is a next-generation GLP-2 receptor agonist engineered for once-weekly subcutaneous dosing in short bowel syndrome with intestinal failure (SBS-IF). It was developed by VectivBio (Ferring subsidiary) and acquired by Ironwood Pharmaceuticals in June 2023 (transaction value ~$1.1 billion). It has orphan drug designations in the US and EU. Phase 3 (STARS-021; NCT05216822) and a long-term extension (STARS-EXT) are ongoing or recently completed. The once-weekly dosing interval is the longest among GLP-2 analogs under development. STARS-021 primary completion was estimated in late 2025.
Identity and composition
| Field | Verified information |
|---|---|
| Preferred name | Apraglutide |
| Key aliases | FE 203799, V-203799 |
| Molecular/sequence identity | GLP-2 analog; multiple amino acid substitutions for extended half-life and DPP-4 resistance |
| Modifications/form | Subcutaneous solution; acetate salt |
| Stable identifiers | UNII: 5QG42Q7Q4V; CAS: 1295353-98-8; DrugBank: DB16699. No unambiguous exact-name PubChem compound was selected in this review. |
| Identity caveats | Distinct from teduglutide and glepaglutide, with different amino-acid substitutions and pharmacokinetics. A prior draft associated CID 137320520 without adequate verification; it is intentionally not used here. |
Development and approval status
| Jurisdiction | Status and indication | Product/source | As of |
|---|---|---|---|
| US (FDA) | Investigational; orphan drug designation for SBS | VectivBio/Ironwood | 2026 |
| EU (EMA) | Investigational; orphan designation | VectivBio/Ironwood | 2026 |
| UK (MHRA) | No marketing authorization | — | 2026 |
Mechanism and pharmacology
GLP-2 receptor agonist. Promotes intestinal mucosal growth, enhances absorptive capacity of the remnant bowel in SBS, reduces gastric emptying and secretion. Extended half-life enables once-weekly dosing, the longest dosing interval among GLP-2 analogs under development for SBS-IF. The mechanism is presumed similar to teduglutide and glepaglutide but with structure-based optimizations for DPP-4 resistance and reduced clearance.
Evidence by claim
| Claim/indication | Stage | Grade | Best human evidence | Main result | Important limitations |
|---|---|---|---|---|---|
| SBS-IF (PS reduction) | Phase 3 | C | Phase 2 (NCT03408132); Phase 3 STARS-021 (NCT05216822) | Phase 2 showed PS reduction in open-label portion | Full phase 3 published results not yet available at time of verification |
| Intestinal microbiota modulation | Exploratory | D | Microbiome substudy (PMID 41903849) | Early ecological changes in gut microbiota with apraglutide | Exploratory endpoint; clinical significance undetermined |
Key studies
| Study | Design/population | Exposure studied | Endpoints and result | Limitations |
|---|---|---|---|---|
| NCT03408132 (phase 2) | Open-label, SBS-IF, dose-ranging | Apraglutide SC once weekly, doses 5–40 mg | PS volume reduction; safety and tolerability | Small sample; no placebo comparator in some portions |
| STARS-021 (NCT05216822) | Phase 3, RCT, N=~120, SBS-IF | Apraglutide SC once weekly vs placebo | PS volume reduction from baseline; enteral autonomy | Primary completion ~2025; full results pending |
| STARS-EXT | Open-label extension | Continued apraglutide | Long-term safety and durability of response | Ongoing |
| Microbiome analysis (PMID 41903849) | Exploratory substudy of intestinal microbiota in SBS-IF | Apraglutide SC once weekly | Early ecological changes observed in gut microbiota | Exploratory; clinical relevance for SBS outcomes not yet determined |
Dose and administration evidence
Approved labeled regimen
No established or recommended human dose.
Studied regimens (not recommendations)
Phase 2: single SC doses up to 40 mg; multiple doses in range 5–40 mg SC once weekly
Phase 3 (STARS-021): weekly SC dose; exact dose arm not publicly confirmed in full
What is not established
No established or recommended human dose.
Safety
Established label risks
Not applicable (investigational).
Human-study signals
GI adverse events: nausea, abdominal pain, diarrhoea
Injection site reactions
Stoma enlargement / stoma-related events
Unknowns and product-quality risks
Long-term safety and immunogenicity profile
Comparative efficacy vs teduglutide and glepaglutide
Research-grade material not equivalent to pharmaceutical product
Interactions and special populations
No established drug interactions
No data in special populations
No pregnancy/lactation data
No paediatric studies
Regulatory, compounding, and sport notes
WADA: S0 — non-approved pharmacological substance. As an unapproved GLP-2 receptor agonist, apraglutide falls under WADA S0 (any pharmacological substance not addressed by other sections of the Prohibited List and not approved by any governmental regulatory authority for human therapeutic use).
Not scheduled
Orphan drug designation in US and EU
Any marketed vial is unapproved investigational material
Ironwood Pharmaceuticals acquired VectivBio in June 2023 for $1.1 billion, indicating significant investment in development
Evidence gaps
Phase 3 confirmatory data from STARS-021 awaited
No head-to-head comparison to teduglutide or glepaglutide
Long-term durability of intestinal adaptation and effect on enteral autonomy
Immunogenicity data limited to early-phase studies
Patient-reported outcome data not yet published
Search notes
Databases and registries: ClinicalTrials.gov, PubMed, Ironwood/VectivBio pipeline
Search terms: apraglutide, FE 203799, short bowel syndrome, GLP-2 analog
Last searched: 2026-08-06
Inclusion emphasis: Phase 2/3 trials, regulatory designations, company disclosures
Sources
ClinicalTrials.gov. Phase 2 Study of Apraglutide in SBS-IF. https://clinicaltrials.gov/study/NCT03408132
ClinicalTrials.gov. STARS-021 Phase 3 Study. https://clinicaltrials.gov/study/NCT05216822
ClinicalTrials.gov. STARS-EXT Extension Study. https://clinicaltrials.gov/study/NCT06222515
Ironwood Pharmaceuticals pipeline (apraglutide). https://www.ironwoodpharma.com/pipeline/
DrugBank DB16699. https://go.drugbank.com/drugs/DB16699
UNII 5QG42Q7Q4V. https://precision.fda.gov/uniisearch/srs/unii/5QG42Q7Q4V
Microbiome analysis in SBS with apraglutide (2025). Clin Nutr ESPEN. PMID 41903849. https://pubmed.ncbi.nlm.nih.gov/41903849/
Systemic pharmacokinetics of therapeutic peptides (apraglutide reviewed). Clin Pharmacokinet. 2025. PMID 41661442. https://pubmed.ncbi.nlm.nih.gov/41661442/
Ironwood Pharmaceuticals acquisition of VectivBio (June 2023). https://www.ironwoodpharma.com/pipeline/