{"id":"ara-290","name":"ARA-290 (cibinetide)","aliases":["cibinetide","ARA 290","pyroglutamate helix B surface peptide","pHBSP"],"url":"https://lyoresearch.com/compounds/ara-290","class":{"id":"immune-peptides","name":"Immune, antimicrobial and repair-signal peptides","url":"https://lyoresearch.com/classes/immune-peptides"},"summary":"ARA-290 is a short peptide copied from a surface of the erythropoietin molecule that signals tissue protection but not red-cell production. Its developer has run small randomised trials in small-fibre neuropathy, mostly in sarcoidosis: in a 64-person, 28-day phase 2, the 4 mg dose measurably increased nerve fibres in the cornea and skin, while pain improved on placebo as much as on drug. No phase 3 has been completed and it is not approved anywhere. The grey market sells it for pain, healing and inflammation on the strength of that early signal.","overall_grade":"C","overall_grade_meaning":"weak human evidence","human_trials":"Phase 2 RCTs in sarcoidosis neuropathy (n=64) and diabetes; no phase 3","regulatory_status":"Not approved; investigational","molecule":{"formula":"C51H84N16O21","molecular_weight":"1257.3","cas":"1208243-50-8","pubchem_cid":91810664,"note":null},"pharmacokinetics":{"basis":"none","route":"Intravenous and subcutaneous in the trials, which report no PK","half_life":"No human pharmacokinetic data located","licensed_regimen":null,"product":null,"source":{"title":"Heij L, et al. Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy: a randomized, double-blind pilot study. Mol Med 2012","url":"https://pubmed.ncbi.nlm.nih.gov/23168581/"}},"outcomes":[{"outcome":"Nerve fibre regeneration (sarcoidosis small-fibre neuropathy)","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"1 phase 2b RCT (n=64, 28 days)","evidence":"Corneal nerve fibre area rose significantly on the 4 mg dose but not on 1 mg or 8 mg, and regenerating skin fibres increased at 4 mg — a surrogate signal, in a short trial, with a non-monotonic dose response.","references":[{"citation":"Culver DA, Dahan A, Bajorunas D, et al. Cibinetide improves corneal nerve fiber abundance in patients with sarcoidosis-associated small nerve fiber loss and neuropathic pain.","where":"Invest Ophthalmol Vis Sci, 2017","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Culver+cibinetide+corneal+nerve+fiber+sarcoidosis+2017"}],"verbatim":{"text":"The placebo-corrected mean change from baseline CNFA (μm2) at day 28 was 109 (95% confidence interval [CI], -429, 647), 697 (159, 1236; P = 0.012), and 431 (-130, 992) in the 1, 4, and 8 mg groups, respectively.","citation":"Culver DA, Dahan A, Bajorunas D, et al. Cibinetide improves corneal nerve fiber abundance in patients with sarcoidosis-associated small nerve fiber loss and neuropathic pain.","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Culver+cibinetide+corneal+nerve+fiber+sarcoidosis+2017"}},{"outcome":"Neuropathic pain","grade":"C","grade_meaning":"weak human evidence","effect_size":"not measurable","adverse":false,"human_studies":"Same trial + earlier phase 2","evidence":"Pain improved in every arm including placebo; the placebo-corrected difference in the 4 mg group did not reach significance.","references":[{"citation":"Culver DA, Dahan A, Bajorunas D, et al. Cibinetide improves corneal nerve fiber abundance in patients with sarcoidosis-associated small nerve fiber loss and neuropathic pain.","where":"Invest Ophthalmol Vis Sci, 2017","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Culver+cibinetide+corneal+nerve+fiber+sarcoidosis+2017"}],"verbatim":{"text":"Pain improved significantly in all groups, with subjects having moderate-severe pain reporting a clinically meaningful placebo-corrected decrease in pain intensity in the 4 mg group (P = 0.157).","citation":"Culver DA, Dahan A, Bajorunas D, et al. Cibinetide improves corneal nerve fiber abundance in patients with sarcoidosis-associated small nerve fiber loss and neuropathic pain.","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Culver+cibinetide+corneal+nerve+fiber+sarcoidosis+2017"}},{"outcome":"Diabetic neuropathy and metabolic control","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"1 small phase 2","evidence":"A 28-day trial in type 2 diabetes with neuropathy reported improved HbA1c and neuropathic symptoms; small, short, not replicated.","references":[{"citation":"Brines M, Dunne AN, van Velzen M, et al. ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes.","where":"Mol Med, 2015","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Brines+ARA+290+type+2+diabetes+neuropathic+symptoms+2015"}]},{"outcome":"Healing, recovery, inflammation (grey-market uses)","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None","evidence":"Extrapolated from the mechanism and from animal work. No human trial.","references":[]},{"outcome":"Adverse effects","grade":"C","grade_meaning":"weak human evidence","effect_size":"not measurable","adverse":true,"human_studies":"Phase 2 trials","evidence":"Well tolerated in the short trials, with no effect on haemoglobin — the point of the design. No long-term data.","references":[{"citation":"Culver DA, Dahan A, Bajorunas D, et al. Cibinetide improves corneal nerve fiber abundance in patients with sarcoidosis-associated small nerve fiber loss and neuropathic pain.","where":"Invest Ophthalmol Vis Sci, 2017","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Culver+cibinetide+corneal+nerve+fiber+sarcoidosis+2017"}]}],"regions":[{"region":"European Union","status":"Unauthorised medicinal product","note":"Investigational only; orphan designation. Supplying it for human use outside a trial is an offence."},{"region":"United States","status":"Not approved","note":"Investigational; orphan designation for sarcoidosis neuropathy. Sold as a 'research chemical'."},{"region":"United Kingdom","status":"Unlicensed medicine","note":"No MHRA licence."},{"region":"Australia","status":"Prescription-only / unapproved","note":"Not on the ARTG."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"A non-approved substance under the non-approved-substances class; it is designed not to stimulate red cells, but that does not exempt it."}],"faq":[{"q":"Does ARA-290 help nerve pain?","a":"In the largest trial, pain improved on placebo as much as on the drug. What improved on the drug — at one dose — was the number of nerve fibres measured in the cornea and skin, which is a surrogate that may or may not matter to how a person feels."},{"q":"Is ARA-290 like EPO?","a":"It is a fragment of EPO chosen to keep the tissue-protective signal and drop the red-cell signal. In trials it did not raise haemoglobin, which was the design goal."},{"q":"Is it approved?","a":"No. It has orphan designations and phase 2 data, and no phase 3 result. It is not approved anywhere and is prohibited in sport as a non-approved substance."}],"references":[{"cite":"Culver DA, Dahan A, Bajorunas D, et al. Cibinetide improves corneal nerve fiber abundance in patients with sarcoidosis-associated small nerve fiber loss and neuropathic pain.","where":"Invest Ophthalmol Vis Sci, 2017","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Culver+cibinetide+corneal+nerve+fiber+sarcoidosis+2017","note":"Phase 2b; 64 patients; 28 days."},{"cite":"Brines M, Dunne AN, van Velzen M, et al. ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes.","where":"Mol Med, 2015","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Brines+ARA+290+type+2+diabetes+neuropathic+symptoms+2015","note":"Small 28-day phase 2."}],"last_reviewed":"2026-09-10","literature_searched_to":"2026-09-10","changelog":[{"date":"2026-09-10","note":"Initial publication. Grade C on phase 2 surrogate data; pain did not separate from placebo."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"}