ARA-290

Overview

ARA-290 (Cibinetide) is a synthetic 11-amino-acid peptide derived from the helix-B surface of erythropoietin (EPO), developed by Araim Pharmaceuticals. It selectively activates the innate repair receptor (IRR) for anti-inflammatory, tissue-protective, and neuroprotective signaling without stimulating erythropoiesis. ARA-290 is not FDA-approved; it has received FDA Fast Track and Orphan Drug designations for sarcoidosis-associated small fiber neuropathy and remains in clinical development as of April 2026.

Mechanism of Action

ARA-290 selectively binds the innate repair receptor (IRR), a heterodimer of EPOR and the beta common receptor (CD131/βcR). Unlike EPO, it does not engage the homodimeric EPOR and therefore does not stimulate erythropoiesis. IRR activation engages JAK2/STAT3, PI3K/Akt, and MAPK pathways, promoting anti-apoptotic gene expression, dampening NF-κB-driven proinflammatory cytokines (TNF-α, IL-6), and supporting Schwann cell survival and axonal regeneration in damaged tissues.

Research Summary

Dahan et al. (Molecular Medicine, 2013, PMID 24136731) conducted a blinded placebo-controlled trial of 28 days of subcutaneous ARA 290 in sarcoidosis patients with documented small nerve fiber loss; treatment improved neuropathic symptoms, increased corneal nerve fiber density on confocal microscopy, altered thermal thresholds, and improved 6-minute walk distance. Brines et al. (Molecular Medicine, 2015, PMID 25387363) reported a placebo-controlled trial of 4 mg daily SubQ ARA 290 for 28 days in type 2 diabetes: the active arm showed improvements in HbA1c, lipid profile, and PainDetect neuropathic symptom scores, with recovery of intraepidermal nerve fiber measurements versus no change on placebo. Heij et al. (2012) and additional Phase 2 work have supported the tissue-protective signal. ARA-290 has not advanced to Phase 3 registration trials and is not FDA-approved.

Dosing Information

Reported Side Effects

• Injection site reactions (erythema, mild pain)
• Headache
• Mild nausea
• Upper respiratory tract symptoms

Research References

• ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density (2013)
• ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes (2015)