C tier · mixed
It has the cleanest development record of the non-approved compounds here - registered phase 2 and 2b randomised trials with objective histological endpoints and an FDA orphan designation - but it never reached phase 3 and development appears to have stalled.
ara-290
ARA-290 is an 11-residue peptide engineered from the helix B surface of erythropoietin to activate the innate repair receptor without erythropoietic activity. Randomised phase 2 trials in sarcoidosis-associated small fibre neuropathy and type 2 diabetes reported improvements in symptoms and in objectively measured corneal nerve fibre metrics, but no phase 3 trial has been conducted.
// we supply this one
available as a research reagent
≥ 99% HPLC · lyophilised powder · batch certificate published. Grade C above is our own and is not adjusted because we stock it.
the explanation
ARA-290 is a small piece designed from the surface of the natural hormone EPO, engineered to protect and repair nerves without the blood-thickening effect EPO has. Mid-stage trials in patients with nerve damage showed measurable regrowth of tiny corneal nerve fibres, but the drug never progressed to the large final-stage trials needed for approval.
regulatory status
not approved; FDA orphan drug designation
Granted US FDA orphan drug designation for sarcoidosis in July 2016 by Araim Pharmaceuticals after completing a phase 2b dose-ranging trial, but no phase 3 programme has been reported and no marketing approval exists in any jurisdiction.
how it works · proposed mechanism
ARA-290 was deliberately engineered to split EPO's tissue-protective activity away from its blood-forming activity.
Innate repair receptor selectivity
It binds the EPOR-beta common receptor heterocomplex rather than the homodimeric EPO receptor that drives red cell production. This is the design feature that avoids EPO's polycythaemia and thrombosis risk.
Small fibre regeneration
Human trials measured increases in corneal nerve fibre area and intraepidermal GAP-43-positive regenerating fibres. These are objective structural endpoints rather than patient-reported outcomes.
Anti-apoptotic tissue protection
Animal work reports reduced apoptosis and inflammation across nerve, kidney, cardiac and wound models. In diabetic mice it improved wound healing with increased VEGF, phospho-Akt and phospho-eNOS.
Immune modulation
In experimental autoimmune neuritis it suppressed lymphocyte proliferation and shifted T cell differentiation. This suggests the effect is not purely neurotrophic.
what’s reported
evidence shape
5 sourcesThe composition of the cited literature by study type. This describes the shape of the evidence, not its quality — and it does not by itself set the grade.
⚠ the catch
Every human trial ran for only 28 days of treatment, so nothing is known about durability, and the programme stalled after phase 2b without a phase 3 despite orphan designation nearly a decade ago. In the phase 2b trial the corneal nerve fibre benefit reached significance only in the highest dose group, and the diabetes trial's nerve fibre effect appeared only in the subgroup with the worst baseline values.
key published findings
- Phase 2b randomised trial (Investigative Ophthalmology and Visual Science, 2017, n=64, 28 days) reported a placebo-corrected corneal nerve fibre area increase of 697 µm² in the 4 mg group at day 28 (P=0.012) and increased intraepidermal GAP-43-positive fibres (P=0.035).
- Randomised double-blind trial in sarcoidosis-associated small fibre neuropathy (Molecular Medicine, 2013, 28 days) reported improved neuropathic symptoms, increased corneal small nerve fibre density, improved temperature sensitivity and improved 6-minute walk test performance.
- Phase 2 randomised controlled trial in type 2 diabetes (Molecular Medicine, 2015; 20(1):658-66, 28 days treatment plus 28 days follow-up) reported improved HbA1c and lipid profiles over 56 days and significant PainDetect improvement, with corneal nerve fibre density increasing only in subjects whose baseline was more than 1 SD below normal, and no change in placebo.
- Preclinical study in genetically diabetic mice (Biochimica et Biophysica Acta Molecular Basis of Disease, 2018) found cibinetide improved wound healing with increased VEGF, phospho-Akt, phospho-eNOS and nitrite/nitrate and reduced malondialdehyde.
- Araim Pharmaceuticals received US FDA orphan drug designation for ARA 290 in sarcoidosis on 5 July 2016 following completion of the phase 2b dose-ranging trial.
limitations of the evidence
- No phase 3 trial has been conducted and the development programme appears inactive despite orphan designation in 2016.
- All human trials were 28-day treatment studies in small populations, leaving durability, long-term safety and clinically meaningful function unaddressed.
- Key efficacy signals were confined to specific dose groups or to baseline-defined subgroups, raising the possibility of chance findings.
identity
| full name | Cibinetide, an 11-amino-acid erythropoietin helix-B surface peptide |
| category | Healing & Repair |
| modality | peptide |
| formula | C51H84N16O21 |
| molar mass | 1257.32 g/mol |
| cas | 1208243-50-8 |
| sequence | QEQLERALNSS |
laboratory handling
| storage | Lyophilised powder is typically stored at -20 °C protected from light; reconstituted laboratory solutions are refrigerated at 2-8 °C for short-term use or aliquoted and frozen to avoid repeated freeze-thaw. |
| solubility | Water-soluble; reconstituted in sterile water, saline or aqueous buffer for laboratory work. |
| co-studied with | Studied largely as a monotherapy against placebo on top of existing standard care, and is not conventionally co-administered with other research peptides. |
Handling information describes laboratory practice for a research reagent. It is not a preparation guide for use in humans.
the receipts
5 citedInvestigative Ophthalmology and Visual Science · 2017 · peer-reviewed
Molecular Medicine · 2013 · peer-reviewed
Molecular Medicine · 2015 · peer-reviewed
Biochimica et Biophysica Acta - Molecular Basis of Disease · 2018 · preclinical
PR Newswire (company announcement) · 2016 · press release
Sources marked tertiary or press release are the weakest citations on this page.
others in Healing & Repair