B7-33 vs Apraglutide
Comprehensive side-by-side comparison of mechanisms, dosing, side effects, and research
Also: B7-33 relaxin, Single-chain relaxin-2 analog
B7-33 is a 27-amino-acid, single-chain peptide cut down from the B-chain of human relaxin-2, the hormone that loosens tissue during pregnancy. Relaxin itself has strong anti-scarring effects but is a complex two-chain molecule that is hard and expensive to make, so an Australian group (Hossain and colleagues, 2016) designed B7-33 as a simpler version. In rodent models it reduced heart and lung fibrosis about as well as full relaxin. It has never been tested in humans.
Also: FE 203799, Once-weekly GLP-2 analog
Apraglutide is a once-weekly GLP-2 analog for short bowel syndrome, originally from VectivBio and now owned by Ironwood Pharmaceuticals. Its phase 3 STARS trial hit its main goal in 2024, but in April 2025 Ironwood said the FDA wanted a confirmatory trial, partly because patients in STARS got less drug exposure than planned due to how doses were prepared and given. That new trial, STARS-2, started in June 2026, so approval is years away (a submission before end of 2029 has been mentioned).
Key Comparison Insights
- Both peptides belong to the Healing category, suggesting similar primary applications.
- Apraglutide has stronger research evidence (Human Trials) compared to B7-33 (Preclinical).
Detailed Comparison
| Attribute | B7-33 | Apraglutide |
|---|---|---|
| Category | Healing | Healing |
| FDA Status | Not FDA Approved | Not FDA Approved |
| Clinical Status | Pre I II III IV FDA | Pre I II III IV FDA |
| Mechanism of Action | B7-33 activates RXFP1, the relaxin receptor, but in an unusual way. In cells that naturally carry RXFP1 (like fibroblasts), it preferentially switches on the pERK1/2 pathway rather than the cAMP pathway, which made it the first described functionally selective (biased) RXFP1 agonist. Its anti-fibrotic action runs through RXFP1 paired with the angiotensin II type 2 receptor, increasing MMP-2, an enzyme that breaks down collagen. In other words, it pushes scar tissue to be broken down rather than built up. Two practical caveats: it binds RXFP1 poorly in standard engineered cell lines, so its potency depends heavily on the cell type, and it is short-lived in serum (roughly 6 minutes in lab tests), which is why researchers have tried fatty-acid versions to stretch its half-life. | Like teduglutide and glepaglutide, apraglutide activates GLP-2 receptors in the gut, signaling the intestinal lining to grow and absorb more. It was engineered for very low clearance and high plasma protein binding, which gives it a much longer half-life. In rat studies its IV half-life was about 159 minutes versus 19 for teduglutide and 16 for glepaglutide, and it kept more gut-growth activity when dosed less often. That is the basis for once-weekly dosing in humans. Same class caveat as the others: long-term stimulation of gut tissue growth carries a theoretical polyp and tumor risk that requires monitoring. |
| Common Dosing | No established human dose Once to twice daily in mouse studies | 2.5-5 mg once weekly by body weight (trial dose) Once weekly |
| Administration | Intraperitoneal or subcutaneous injection (including osmotic minipumps) in rodents | Subcutaneous injection once weekly |
| Typical Duration | 1-2 weeks in most rodent studies | 24-week primary endpoint, with treatment continued to week 48 and beyond in STARS |
| Best Time to Take | No evidence-based timing | Same day each week (trial schedule) |
Possible Side Effects May vary by individual |
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| Research Summary | The founding paper (Hossain et al., Chemical Science, 2016) reported that B7-33 prevented or reversed organ fibrosis and dysfunction in three rodent models of heart or lung disease with potency similar to full relaxin-2, and, unlike native relaxin, it did not promote prostate tumor growth in mice. That last point matters because relaxin has been linked to tumor growth. Later mouse work extended the findings: Devarakonda et al. (Journal of the American Heart Association, 2020) gave 0.25 mg/kg twice daily by injection after a heart attack and found smaller infarcts, better heart function, and less fibrosis at 7 days. A 2023 follow-up from the original group confirmed that B7-33 cannot be shortened further without losing receptor binding. Important context: the full hormone (serelaxin) went all the way to a large phase 3 trial in acute heart failure (RELAX-AHF-2) and failed both primary endpoints, a reminder that strong animal anti-fibrotic data in this family have not translated easily to people. For B7-33 itself there are no human studies, no human pharmacokinetics, and no human safety data. | STARS (NCT04627025) randomized 164 adults with SBS and intestinal failure 2:1 to weekly apraglutide (2.5 mg or 5 mg by body weight) or placebo. Topline results in February 2024: weekly parenteral support volume fell 25.5% versus 12.5% on placebo at week 24 (p=0.001). In stoma patients the gap was bigger (25.6% vs 7.8%), and 43% vs 27.5% gained at least one day a week off IV support. But the colon-in-continuity endpoints missed, and enteral autonomy at week 48 (12.5% vs 7.4%) was not significant. Discontinuation for side effects was low (3.6% vs 1.9%). While preparing the NDA, Ironwood found exposure in STARS was lower than intended because of dose preparation and administration, and in April 2025 said the FDA required a confirmatory trial. STARS-2 is a 24-week, placebo-controlled trial of about 124 patients (NCT07742735), started June 2026. So: a positive phase 3 on paper, with a dosing problem that undercuts confidence, and no approval in sight before the end of the decade. |
Frequently Asked Questions: B7-33 vs Apraglutide
What is the difference between B7-33 and Apraglutide?
B7-33 is a healing peptide that b7-33 is a 27-amino-acid, single-chain peptide cut down from the b-chain of human relaxin-2, the hormone that loosens tissue during pregnancy. relaxin itself has strong anti-scarring effects but is a complex two-chain molecule that is hard and expensive to make, so an australian group (hossain and colleagues, 2016) designed b7-33 as a simpler version. in rodent models it reduced heart and lung fibrosis about as well as full relaxin. it has never been tested in humans. Apraglutide is a healing peptide that apraglutide is a once-weekly glp-2 analog for short bowel syndrome, originally from vectivbio and now owned by ironwood pharmaceuticals. its phase 3 stars trial hit its main goal in 2024, but in april 2025 ironwood said the fda wanted a confirmatory trial, partly because patients in stars got less drug exposure than planned due to how doses were prepared and given. that new trial, stars-2, started in june 2026, so approval is years away (a submission before end of 2029 has been mentioned). The main differences lie in their mechanisms of action and clinical applications.
Which is better, B7-33 or Apraglutide?
Neither is universally "better" - the choice depends on your specific goals. B7-33 is typically used for healing purposes, while Apraglutide is used for healing. Always consult with a healthcare provider to determine which may be appropriate for your situation.
Can B7-33 and Apraglutide be used together?
Some peptide protocols combine multiple compounds for synergistic effects. However, using B7-33 and Apraglutide together should only be considered under medical supervision, as both compounds have their own side effect profiles and potential interactions. Research on their combined use may be limited.