ARA-290 / Cibinetide
Evidence: B — Meaningful Human EvidenceRepair / Tissue Healing
Key facts
- Research areaRepair / Tissue Healing
- Study records146 human
- Study-at-a-Glance1published summaries
- Last updated2026-07-30
Evidence Snapshot
What this grade covers
A for identity and current FDA category status; B/C for small indication-specific human trials and surrogate findings; D/E for established neuropathy treatment, broad tissue repair, metabolic treatment, approval, safety, or dosing.
Regulatory Context
Investigational erythropoietin-derived peptide; not FDA-approved.
In Plain English
A quick, research-focused overview. It does not replace, and cannot outrank, the detailed evidence below.
What is it?
ARA-290, later developed as cibinetide, is an erythropoietin-derived peptide engineered to activate tissue-protective signaling without stimulating red-blood-cell production. Several small phase 2 studies evaluated neuropathic symptoms, corneal nerve measures, metabolic endpoints, and diabetic macular edema.
Why are researchers interested in it?
ARA-290/cibinetide was designed from the helix-B surface of erythropoietin. It is studied as a selective agonist of the innate repair receptor, commonly described as a heteromer involving the erythropoietin receptor and beta-common receptor, with proposed anti-inflammatory and tissue-protective signaling that lacks conventional erythropoietic activity.
What does the evidence look like?
Evidence grade B. Evidence types and limitations are separated below.
Biggest things to know
Published human studies were small and short; long-term safety is not established.
Research Takeaway
ARA-290 and cibinetide are names for the same 11-amino-acid nonerythropoietic peptide derived from an erythropoietin helix and designed to engage tissue-protective innate-repair signaling without stimulating red-cell production.
Evidence boundary: This identity must not be conflated with erythropoietin itself.
See all 6 evidence claims →Quick Summary
ARA-290, later developed as cibinetide, is an erythropoietin-derived peptide engineered to activate tissue-protective signaling without stimulating red-blood-cell production. Several small phase 2 studies evaluated neuropathic symptoms, corneal nerve measures, metabolic endpoints, and diabetic macular edema.
Mechanism & Research Overview
ARA-290/cibinetide was designed from the helix-B surface of erythropoietin. It is studied as a selective agonist of the innate repair receptor, commonly described as a heteromer involving the erythropoietin receptor and beta-common receptor, with proposed anti-inflammatory and tissue-protective signaling that lacks conventional erythropoietic activity.
Mechanism pathway
Relationship-support labels describe the type and directness of the research available, not proof of safety or effectiveness. Indirectly supported, inferred and uncertain relationships are not equivalent to directly supported ones.
- CompoundARA-290 / Cibinetide
- Supported indirectly (Indirectly supported relationship)Biological targetCD131 receptorReceptor
- Leads toPathwayImmune & Inflammatory Signaling
Relationship details
- ARA-290 / Cibinetide → CD131 receptor — Supported indirectlyARA-290/cibinetide effects in multiple preclinical models depend on beta-common receptor (CD131) signaling, supported by knockout and siRNA loss-of-function evidence; this does not establish direct ARA-290-CD131 binding.
Evidence Claims
Individual scientific statements drawn from the sources cited below, each shown with the specific evidence boundary that statement does not establish.
Supported
ARA-290 and cibinetide are names for the same 11-amino-acid nonerythropoietic peptide derived from an erythropoietin helix and designed to engage tissue-protective innate-repair signaling without stimulating red-cell production.
Does not establish
Evidence boundary: This identity must not be conflated with erythropoietin itself.
Sources: ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density; CIBINETIDE / ARA-290 substance record
Supported
Randomized human studies reported improvements in neuropathic symptoms and small-nerve-fiber measures in sarcoidosis-associated and diabetic small-fiber neuropathy populations.
Does not establish
Evidence boundary: These small studies do not establish broad neuroregenerative efficacy across unrelated disorders.
Sources: ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density; ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes; Cibinetide Improves Corneal Nerve Fiber Abundance in Patients With Sarcoidosis-Associated Small Nerve Fiber Loss and Neuropathic Pain
Supported
Cibinetide has been clinically investigated but is not established in this package as an FDA-approved therapeutic product; an FDA UNII identifies the substance but does not imply approval.
Does not establish
Evidence boundary: Clinical-trial registration and substance registration are not marketing authorization.
Sources: Study of Efficacy of ARA 290 on Corneal Nerve Fiber Density and Neuropathic Symptoms of Sarcoidosis Patients; CIBINETIDE / ARA-290 substance record
Supported
Short controlled studies did not identify the hematopoietic adverse effects characteristic of erythropoietin, but the trials are too small and short to define a complete long-term safety profile.
Does not establish
Evidence boundary: Absence of a major signal in small trials does not establish long-term safety.
Sources: ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density; ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes; Cibinetide Improves Corneal Nerve Fiber Abundance in Patients With Sarcoidosis-Associated Small Nerve Fiber Loss and Neuropathic Pain
Supported
The human evidence supports a neuropathy research signal but does not establish cibinetide as a proven treatment for generalized pain, anti-aging, athletic recovery, or systemic tissue repair.
Does not establish
Evidence boundary: Mechanistic tissue-protection language must not be converted into unsupported indications.
Sources: ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density; ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes; Cibinetide Improves Corneal Nerve Fiber Abundance in Patients With Sarcoidosis-Associated Small Nerve Fiber Loss and Neuropathic Pain
Supported
Only exact regimens from named clinical trials may appear as Study/Trial Dosing, with no consumer dosing or self-administration recommendations.
Does not establish
Evidence boundary: Trial dosing does not imply an approved or advisable regimen outside the study.
Sources: ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density; ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes; Study of Efficacy of ARA 290 on Corneal Nerve Fiber Density and Neuropathic Symptoms of Sarcoidosis Patients
Safety & Evidence Limitations
Considerations reported in the sources cited on this page — not a complete list of every possible risk, and not medical advice.
Safety Consideration
Published human studies were small and short; long-term safety is not established.Safety Consideration
Improvements in corneal nerve-fiber density are surrogate or exploratory findings and do not automatically prove durable clinical benefit.Safety Consideration
The compound remains investigational and no approved indication has been established.Safety Consideration
Potential class or receptor-related effects and interactions have not been comprehensively characterized.Safety Consideration
Short-term small trials did not show the hematocrit-raising profile expected from erythropoietin, consistent with nonerythropoietic design, but this does not establish comprehensive safety. Important uncertainties include limited participant numbers and exposure duration; unknown long-term receptor effects; cardiovascular and hemodynamic effects; hematologic effects not detectable in small studies; immune and inflammatory pathway modulation; angiogenic or proliferative consequences; hepatic, renal, retinal, neurologic, reproductive, pregnancy, and developmental effects; interaction with erythropoietin, diabetes drugs, anticoagulants, immunomodulators, and cancer therapy; peptide aggregation, impurities, immunogenicity, sterility, and endotoxins; free-form versus salt/formulation differences; and absence of a completed confirmatory safety program. Lack of erythropoiesis does not eliminate all cardiovascular or cancer-related risk.
Research Areas Being Studied
Research areas discussed on this page reflect the Repair / Tissue Healing category and the sources cited below.
Findings Reported in Studies
Educational summary only — reported in cited studies, not a claim of proven benefit.
Show findings from 6 human studies
- A Phase 2 clinical trial on the use of cibinetide for the treatment of diabetic macular edema (2020):
- Cibinetide Improves Corneal Nerve Fiber Abundance in Patients With Sarcoidosis-Associated Small Nerve Fiber Loss and Neuropathic Pain (2017):
- ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes (2015):
- ARA 290 for treatment of small fiber neuropathy in sarcoidosis (2014):
- ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density (2013):
- Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy (2012):
Study Tables by Evidence Type
14 study records · 1 with a Study-at-a-Glance summary
- Human Studies & Clinical Data 6
- Animal / Cell / Preclinical Data 2
- Regulatory Documents & Official Trial Registries 6
Human Studies & Clinical Data(6)
A Phase 2 clinical trial on the use of cibinetide for the treatment of diabetic macular edema
2020PMID 32674280 · DOI 10.3390/jcm9072225
- Population / Model
- Treatment-naive patients with diabetic macular edema
- Dose / Duration / Finding
Small phase 2 study evaluated ocular and systemic outcomes; it was exploratory and not definitive evidence of clinical efficacy.
- Study/Trial Dosing:
- 4 mg subcutaneously once daily.
- Duration:
- 12 weeks
Safety note
Small sample; systemic and long-term safety remain incompletely characterized.
Cibinetide Improves Corneal Nerve Fiber Abundance in Patients With Sarcoidosis-Associated Small Nerve Fiber Loss and Neuropathic Pain
2017PMID 28475703 · DOI 10.1167/iovs.16-21291
- Population / Model
- Patients with sarcoidosis-associated small-fiber loss and neuropathic pain
- Dose / Duration / Finding
Cibinetide increased corneal and cutaneous small-nerve-fiber abundance in patients with sarcoidosis-associated small-fiber loss. The findings support biological activity but do not constitute approval.
- Study/Trial Dosing:
- 1 mg, 4 mg, or 8 mg subcutaneously once daily.
- Duration:
- 28 days
Safety note
Short-duration study; long-term safety and clinical relevance of surrogate endpoints remain uncertain.
ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes
2015PMID 25387363 · DOI 10.2119/molmed.2014.00215
- Population / Model
- Adults with type 2 diabetes and painful neuropathy
- Dose / Duration / Finding
In type 2 diabetes with painful neuropathy, ARA-290 was associated with improvement in neuropathic symptoms and selected metabolic measures over a short trial. No major safety issue was identified, but larger confirmatory studies were required.
- Study/Trial Dosing:
- 4 mg subcutaneously once daily.
- Duration:
- 28 days of treatment plus 28 days of observation
Safety note
No major signal was identified in this small study, but sample size and duration were insufficient to establish long-term safety.
ARA 290 for treatment of small fiber neuropathy in sarcoidosis
2014PMID 24555851
- Population / Model
- Patients with sarcoidosis-associated small-fiber neuropathy
- Dose / Duration / Finding
Clinical evaluation reported improvement in neuropathic-pain symptoms during ARA-290 treatment.
Safety note
Limited sample size and investigational setting.
ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density
2013PMID 24136731 · DOI 10.2119/molmed.2013.00122
- Population / Model
- Patients with sarcoidosis-associated small-fiber neuropathy
- Dose / Duration / Finding
In patients with sarcoidosis-associated small-fiber neuropathy, 28 days of ARA-290 improved neuropathic symptoms and was associated with increased corneal nerve-fiber density. The trial was small and exploratory.
- Study/Trial Dosing:
- Study-defined intravenous ARA-290 regimen; see publication.
- Duration:
- 4 weeks with follow-up
Safety note
Small, short-duration study; findings require confirmation.
Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy
2012PMID 23168581 · DOI 10.2119/molmed.2012.00332
- Population / Model
- 22 patients with sarcoidosis and small-fiber-neuropathy symptoms
- Dose / Duration / Finding
Pilot randomized data reported improvement in neuropathic symptoms and supported further evaluation.
- Study/Trial Dosing:
- 2 mg intravenously three times weekly.
- Duration:
- 4 weeks
Safety note
Small sample and short exposure limit safety conclusions.
Animal / Cell / Preclinical Data(2)
ARA290, a peptide derived from the tertiary structure of erythropoietin, produces long-term relief of neuropathic pain in rats
2011PMID 21873879
- Population / Model
- Rat peripheral-nerve-injury model
- Dose / Duration / Finding
ARA290 produced long-lasting relief of tactile and cold allodynia in rats and wild-type mice; in mice lacking the β-common receptor, no ARA290 effect was observed, supporting β-common-receptor-dependent signaling without establishing direct ARA290-CD131 binding.
Show full finding
Safety note
Preclinical result; translation to humans is uncertain.
Effect of insulin and an erythropoietin-derived peptide on diabetic neuropathy in rats
2011PMID 21872588
- Population / Model
- Diabetic rat neuropathy model
- Dose / Duration / Finding
ARA-290 was evaluated for tissue-protective effects in diabetic neuropathy models.
Safety note
Animal evidence does not establish human efficacy or safety.
Regulatory Documents & Official Trial Registries(6)
Study of Efficacy of ARA 290 on Corneal Nerve Fiber Density and Neuropathic Symptoms of Sarcoidosis Patients
2014NCT02039687
Study-at-a-Glance available
- Population / Model
- Adults with sarcoidosis-associated neuropathy
- Dose / Duration / Finding
The registry documents clinical investigation of ARA-290 in sarcoidosis-associated neuropathy. Registration and completion do not imply FDA approval.
Key takeaway
In this trial of 64 people with sarcoidosis nerve damage and pain, cibinetide (ARA 290) increased corneal nerve fibre area versus placebo only at the 4 mg dose. Pain did not clearly improve more than with placebo.
Study at a Glance
Study at a Glance
Plain-language summary of: Study of Efficacy of ARA 290 on Corneal Nerve Fiber Density and Neuropathic Symptoms of Sarcoidosis Patients
Does cibinetide (ARA 290) help the nerve damage and pain that can come with sarcoidosis?
Evidence status
What was being studied?
Whether cibinetide (ARA 290), a small peptide designed to activate the body's tissue-repair receptor, can improve nerve damage and nerve-related pain in people with sarcoidosis. The main measure was a scan-based count of the area of nerve fibres in the cornea, used as a stand-in for small-nerve-fibre loss.
Who participated?
64 adults aged 18 to 70 with sarcoidosis, nerve pain (a score of 4 or more on a 0-10 pain scale) and signs of small-nerve-fibre loss. 16 were assigned to each of three cibinetide doses (1, 4 or 8 mg a day) and 16 to placebo. 62 were in the results tables (14 in the 8 mg group); the average age was about 51, 32 were women and 30 men, and 61 of 62 were White.
How was the study done?
A randomized, double-blind, placebo-controlled dose-ranging trial, called Phase 2 in the registry and phase 2b in the journal abstract. Participants injected cibinetide or placebo under the skin once a day for 28 days and were followed for up to 12 more weeks. The main measure was the change in corneal nerve fibre area, measured by a non-invasive eye scan (corneal confocal microscopy), from the start to day 28. Secondary measures included a 6-minute walk, skin-biopsy nerve fibre density, and pain and symptom questionnaires. This summary uses the ClinicalTrials.gov record with posted results and the journal abstract; the full paper was not reviewed.
Key results
Corneal nerve fibre area changed by -64.3 square micrometres on 1 mg, +533.8 on 4 mg, +203.8 on 8 mg and -170.0 on placebo. The journal abstract gives the placebo-corrected differences as 109 (95% CI -429 to 647) for 1 mg, 697 (159 to 1236, P=0.012) for 4 mg and 431 (-130 to 992) for 8 mg, so only the 4 mg group was statistically significant. Pain scores fell in every group including placebo (average pain severity change -0.594, -1.167 and -1.115 on the three doses versus -0.922 on placebo), and the abstract reports no significant placebo-corrected pain benefit for the 4 mg group (P=0.157). Walking distance rose by 17.7 to 19.3 metres on cibinetide and 1.2 metres on placebo, with no statistical test given in the registry.
| Measure | Group | Timepoint | Reported value |
|---|---|---|---|
| Change in corneal nerve fibre area, square micrometres (primary endpoint) | Cibinetide 1 mg a day (n=16) | Baseline to day 28 | -64.3 (SD 759.9)Placebo-corrected difference 109 (95% CI -429 to 647), from the journal abstract |
| Change in corneal nerve fibre area, square micrometres (primary endpoint) | Cibinetide 4 mg a day (n=16) | Baseline to day 28 | +533.8 (SD 1110.02)Placebo-corrected difference 697 (95% CI 159 to 1236), P=0.012, from the journal abstract |
| Change in corneal nerve fibre area, square micrometres (primary endpoint) | Cibinetide 8 mg a day (n=14) | Baseline to day 28 | +203.8 (SD 641.2)Placebo-corrected difference 431 (95% CI -130 to 992), from the journal abstract |
| Change in corneal nerve fibre area, square micrometres (primary endpoint) | Placebo (n=16) | Baseline to day 28 | -170.0 (SD 633.0) |
| Change in average pain severity (Brief Pain Inventory, 0-10) | 1 mg / 4 mg / 8 mg / placebo | Baseline to day 28 | -0.594 / -1.167 / -1.115 / -0.922Pain fell in every group, including placebo. |
| Change in 6-minute walk distance, metres | 1 mg / 4 mg / 8 mg / placebo | Baseline to day 28 | +19.3 / +17.7 / +18.2 / +1.2No statistical test is given in the registry. |
| Change in skin-biopsy nerve fibre density, fibres per mm | 1 mg / 4 mg / 8 mg / placebo | Baseline to day 28 | +0.5 / +0.4 / -0.3 / +0.8 |
What does this mean?
Safety findings
At least one treatment-emergent adverse event was reported by 14 of 16 people on 1 mg, 11 of 16 on 4 mg, 12 of 14 on 8 mg and 12 of 16 on placebo. Serious events were reported in 2 of 16 people on 1 mg (syncope, headache, chest tightness, shortness of breath and small bowel enteritis across the group), none on 4 mg, 1 of 14 on 8 mg (suicidal ideation) and none on placebo. One person in the 8 mg group stopped because of an adverse event. Headache was reported by 3, 3 and 2 people on the three doses and by none on placebo; injection-site pain was reported by 1, 1 and 1 people versus 4 on placebo. The registry does not report a death count.
Important limitations
- The main endpoint is a scan-based stand-in (surrogate) for nerve-fibre loss, not how people felt or functioned.
- Only the 4 mg dose differed significantly from placebo, and the response did not rise steadily with dose (the 8 mg group changed less than the 4 mg group).
- Pain improved in every group, including placebo, and the abstract reports no significant placebo-corrected pain benefit at 4 mg (P=0.157).
- Small groups of 14 to 16 people and a 28-day treatment period; the walking and nerve-density results have no statistical tests in the registry.
- 62 of the 64 enrolled people appear in the results tables; two in the 8 mg group had a treatment assignment that could not be confirmed.
- Only the journal abstract was reviewed, not the full paper, and the trial was run by the drug's developer.
Regulatory context
- Investigational use studied here
- Cibinetide (ARA 290) was studied as an investigational treatment for neuropathy associated with sarcoidosis.
A search of Drugs@FDA for cibinetide and ARA 290 (accessed 2026-10-08) found no application or approved product.
Sources
- Trial record
- ClinicalTrials.gov NCT02039687 — ClinicalTrials.gov
- Primary results source
- Investigative Ophthalmology & Visual Science 2017 trial report (PubMed abstract) (peer-reviewed report of this trial; only the abstract was reviewed) — PubMedGroup-level results come from ClinicalTrials.gov; the placebo-corrected differences come from the journal abstract.
- Sources reviewed
- Trial registry record with posted results · Abstract only — full text not reviewed.
Other sources for this study (1)
- FDA Drugs@FDA search for cibinetide / ARA 290 (accessed 2026-10-08) — Regulator (FDA / EMA) · No FDA application or approved product was found for either name.Content reviewed for this summary
This summary is a plain-language reading aid written by MitoCore. It does not replace the original study, which remains the authoritative source. Research information only, not medical advice.
503A Bulk Drug Substances Categories, Updated May 14, 2026
2026- Population / Model
- Dose / Duration / Finding
Thymalin was not identified on the reviewed current FDA 503A or 503B bulk-substance category lists or FDA peptide safety table; Cibinetide (ARA-290) is listed in Category 3, meaning it was nominated without adequate support for FDA evaluation. Absence from those lists, or Category 3 status, is not approval, a safety determination, or authorization to compound, and Category 3 is not the Category 1 pathway under which FDA described interim enforcement discretion.
Show full finding
CIBINETIDE / ARA-290 substance record
2026- Population / Model
- Dose / Duration / Finding
FDA GSRS identifies ARA-290 and cibinetide as synonyms for the same 11-amino-acid peptide. FDA states that UNII availability does not imply regulatory review or approval.
FDA UNII: 9W5677JKDA. FDA URL: https://precision.fda.gov/uniisearch/srs/unii/9W5677JKDA
The use of ARA290 for the treatment of diabetic macular edema
2024NCT06626971
- Population / Model
- Participants with diabetic macular edema
- Dose / Duration / Finding
Current registry record; a registry listing is not evidence of completed efficacy results.
Effects of ARA 290 in type 2 diabetes
2013NCT01933529
- Population / Model
- Adults with type 2 diabetes and neuropathy
- Dose / Duration / Finding
Official registry for the controlled type 2 diabetes study.
PubChem Cibinetide Record
- Population / Model
- Dose / Duration / Finding
PubChem's Cibinetide compound record establishes the identity of the 11-amino-acid synthetic peptide derived from the three-dimensional structure of erythropoietin. Used for identity verification only, not efficacy evidence.
Anecdotal Reported Patterns — Not Medical Advice
Anecdotal Reported Patterns — Not Medical Advice
Reported dosing patterns are included for educational context only. They are self-reported, unverified, not medical advice, and not instructions for human use. Community-submitted patterns are not yet available in this Phase 1 prototype; this section is a placeholder reserved for moderated, aggregated community data.
Lab Markers to Discuss With a Clinician
Educational topics only — not self-monitoring instructions.
FAQ
Disclaimer
Educational information only. This page summarizes published and official research and does not provide medical advice, a recommendation, or instructions for human use.
Educational use only. This content is provided for informational and research-summary purposes only. It is not medical advice, not a treatment recommendation, not a dosing guide, and not a substitute for care from a licensed medical professional. Nothing here is intended to diagnose, treat, cure, prevent, or mitigate disease. Reported dosing patterns, when shown elsewhere on the site, must be labeled either as Study / Trial Dosing or Anecdotal Reported Patterns — Not Medical Advice. Community reports are self-reported, unverified, and not scientific proof.
Community-reported experiences, once enabled, must be displayed only as moderated, anonymized, or aggregated data. They are anecdotal, self-reported, unverified, and should never be presented as proof of safety, efficacy, or expected results.
Content status: Published. Last updated 2026-07-30.
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