ARA-290

What it is

ARA-290 (cibinetide) is an 11-amino-acid synthetic peptide modelled on the helix B surface of erythropoietin, also called pyroglutamate helix B surface peptide. It was designed to keep erythropoietin's tissue-protective signalling without stimulating red blood cell production, and has been studied in Phase 2 trials of small nerve fibre loss in sarcoidosis, painful neuropathy in type 2 diabetes, and diabetic macular oedema. It is not an approved medicine in any market.

How it works

ARA-290 selectively activates the innate repair receptor, a complex of the erythropoietin receptor and the beta common receptor (CD131) that is induced by injury or inflammation, rather than the erythropoietin receptor homodimer that drives red cell production. Despite a plasma half-life of about 2 minutes, it is reported to trigger sustained anti-inflammatory and repair effects in animal models.

Regulatory status

1. Cosmetic ingredient
2. Research compound
3. In clinical trials
4. Approved medicine

Not approved as a medicine by the FDA or the EMA. Some are registered in individual countries. Supplied for laboratory research only.

What published research is studying

• Small nerve fibre loss and neuropathic pain in sarcoidosis (Phase 2 and Phase 2b)
• Corneal nerve fibre regrowth measured by corneal confocal microscopy as a surrogate endpoint
• Metabolic control and painful neuropathy in type 2 diabetes (Phase 2)
• Diabetic macular oedema (small Phase 2 study)

Key findings

1. 01

   In a randomised, double-blind pilot trial in 22 patients with sarcoidosis and small fibre neuropathy symptoms, 4 weeks of intravenous ARA-290 reduced the small fibre neuropathy screening list score by 11.5 points versus 2.9 with placebo, while pain and fatigue scores improved equally in both groups.

   Heij L et al., Mol Med 2012
2. 02

   In a blinded, placebo-controlled trial in patients with sarcoidosis-associated small nerve fibre loss, 28 days of daily subcutaneous ARA-290 improved neuropathic symptoms and was associated with increased corneal small nerve fibre density and greater 6-minute walk test distance.

   Dahan A et al., Mol Med 2013
3. 03

   In a 28-day Phase 2b randomised trial in 64 patients with sarcoidosis-associated small nerve fibre loss and neuropathic pain, only the 4 mg arm showed a significant placebo-corrected gain in corneal nerve fibre area (697 µm², p = 0.012), and the placebo-corrected pain reduction in participants with moderate to severe pain did not reach significance (p = 0.157).

   Culver DA et al., Invest Ophthalmol Vis Sci 2017
4. 04

   In a Phase 2 placebo-controlled trial in type 2 diabetes with painful neuropathy, 28 days of daily subcutaneous ARA-290 was associated with improved HbA1c and lipid profiles across a 56-day observation period and with significant improvement in PainDetect neuropathic symptom scores.

   Brines M et al., Mol Med 2015
5. 05

   In a 12-week Phase 2 study in 9 patients with diabetic macular oedema (8 completed), cibinetide produced no mean improvement in visual acuity or central retinal thickness, and no serious adverse events were reported.

   Lois N et al., J Clin Med 2020

How strong is the evidence?

Common questions