Innate Repair Receptor Agonist · EPO-Derived · Protocol Guide
ARA-290: The Honest Repair Peptide Guide
ARA-290 (cibinetide) is an 11-amino-acid fragment of erythropoietin engineered to trigger tissue repair without EPO's blood-thickening effect. Its human evidence is small and specific: Phase 2 trials in nerve-damage pain. This guide draws that line clearly.
- FDA Status
- Investigational, 503A Compounded
- Pharmacy
- Optimal Balance Pharmacy (503A licensed)
- Medical Service
- RxPepsDirect, physician-supervised
- Access
- 28 U.S. States
Our promise: The human evidence for ARA-290 is a handful of small Phase 2 trials in sarcoidosis and diabetic nerve pain, almost all run by the company that developed it. We say where that data stops and where the general recovery claims become extrapolation.
Medically reviewed by Dr. Jonathan Snipes, MD. Last reviewed June 8, 2026.On this page
Section 01
What ARA-290 Actually Is
ARA-290, also called cibinetide, is a synthetic 11-amino-acid peptide that copies one small surface of erythropoietin (EPO). It was engineered by Anthony Cerami and Michael Brines, the researchers who first showed that EPO does two separate jobs, and later commercialized by Araim Pharmaceuticals. The premise is simple and well-documented: EPO builds red blood cells through one receptor, and it protects and repairs injured tissue through a different one. ARA-290 was designed to do only the second job.
In a 2008 study, Brines and colleagues mapped the tissue-protective activity of EPO to a region called helix B and showed that an 11-amino-acid peptide from the water-facing side of that helix kept EPO's repair effects in models of stroke, nerve injury, and kidney damage while producing no increase in red cells. ARA-290 is that peptide. It is, by design, non-erythropoietic.
What ARA-290 cannot do is worth stating plainly. It is not a blood booster and does not raise hematocrit. It is not anabolic. It produces no felt, subjective effect the way a GH secretagogue or a neuroactive peptide does. Its action is cellular: it switches on a repair program and an anti-inflammatory response that play out over weeks.
11
Amino acids, copied from the aqueous face of EPO's helix B
2008
Year the nonerythropoietic helix-B peptide was characterized (PNAS)
64
Patients in the largest randomized trial to date (Phase 2b, sarcoidosis SFN)
503A
Pathway for U.S. compounded access under physician prescription
Section 02
Who It Is Actually For
The studied population is narrow and specific. The wider use cases are reasonable inferences from the mechanism, but they have not been tested in trials, and the honest framing matters here more than usual.
| Profile | Primary Motivation | Evidence Basis | Fit |
|---|---|---|---|
| Sarcoidosis Small Fiber Neuropathy | Reduce neuropathic pain, repair small nerve fibers | The actual trial population. Phase 2 and Phase 2b randomized data. | Best Studied |
| Diabetic / Metabolic Small Fiber Neuropathy | Nerve repair, reduced neuropathic symptoms | Studied as a related population in the corneal nerve fiber work. | Moderate Fit |
| Other Neuropathic Pain | Symptom relief where standard options have failed | Mechanistically plausible, not directly trialed for these causes. | Exploratory |
| General Recovery / Anti-Inflammatory Use | Tissue repair, inflammation reduction, biohacking goals | Extrapolated from preclinical models and the neuropathy data. | Speculative |
| Athlete Subject to Anti-Doping Testing | Recovery support during training | EPO-derived molecule, status uncertain under anti-doping rules. | Confirm Status First |
Profile
Primary Motivation
Evidence Basis
Fit
Profile
Primary Motivation
Evidence Basis
Fit
Profile
Primary Motivation
Evidence Basis
Fit
Profile
Primary Motivation
Evidence Basis
Fit
Profile
Primary Motivation
Evidence Basis
Fit
Section 02
How ARA-290 Works
ARA-290 binds the innate repair receptor, a heterocomplex of the EPO receptor and CD131. That receptor sits on immune cells, nerve tissue, and endothelium, and it is upregulated where tissue is injured or inflamed. Activating it shifts cells out of an inflammatory state and into a repair state.
Innate Repair Receptor
ARA-290 selectively activates the EPO-receptor / CD131 heterocomplex, not the homodimer that drives red cell production. This receptor selectivity is what separates its repair effect from EPO's blood effect.
Anti-Inflammatory Switch
In preclinical work, ARA-290 dampens pro-inflammatory cytokine signaling and pushes immune cells, including macrophages, toward a repair-oriented phenotype. The result is less local inflammation around damaged tissue.
Nerve Fiber Repair
In the sarcoidosis trials, ARA-290 increased corneal nerve fiber area and the number of regenerating intraepidermal nerve fibers (GAP-43 positive). These are objective, measurable signals of small nerve fibers actually regrowing.
No Erythropoiesis
By skipping the EPO receptor homodimer, ARA-290 does not stimulate red cell production. Across the trials, hematocrit and hemoglobin did not rise. This removes the clotting and stroke concerns that limit high-dose EPO for tissue protection.
Section 03
What the Evidence Shows
This is the section that matters most for ARA-290, because the gap between the mechanism and the proof is wider than the marketing usually admits. Here is the actual human record, in order.
| Study | Design | Key Finding | Strength |
|---|---|---|---|
| Brines 2008 (PNAS) [1] | Preclinical, animal models | The 11-amino-acid helix-B peptide is tissue-protective in stroke, nerve, and kidney injury, and is not erythropoietic. | Foundational, Preclinical |
| Heij 2012 (Mol Med) [2] | Pilot RCT, 22 patients, 2 mg IV 3x/week, 4 weeks | Significant improvement in small fiber neuropathy symptom score and SF-36 pain and physical function vs placebo. No safety concerns. | Randomized, Small |
| Culver 2017 (IOVS) [3] | Phase 2b RCT, 64 patients, 1 / 4 / 8 mg/day SC, 28 days | The 4 mg group significantly increased corneal nerve fiber area (P = 0.012) and regenerating skin nerve fibers. Pain improved in all groups, including placebo. | Phase 2b, Mixed |
| van Velzen 2014 (review) [4] | Review of the Phase 2 program | Summarizes consistent neuropathic symptom improvement and an excellent safety profile across the sarcoidosis trials. | Narrative Review |
Study
Design
Key Finding
Strength
Study
Design
Key Finding
Strength
Study
Design
Key Finding
Strength
Study
Design
Key Finding
Strength
Section 04
Realistic Expectations
ARA-290 is a slow, quiet compound. There is no day-one effect to chase. If it is going to help, it does so by gradually repairing nerve tissue and lowering inflammation, which is a process measured in weeks.
No Felt Effect
Expect to feel nothing. ARA-290 acts on cellular repair pathways, not on receptors that produce a subjective response. The absence of an early effect is normal and tells you nothing about whether you will respond.
Early Symptom Signals
In the sarcoidosis trials, responders began reporting lower neuropathic pain scores around the four-week mark. This is the earliest point at which a real change tends to surface.
Repair Phase
Continued symptom reduction in responders. Nerve fiber regrowth is inherently slow, so the objective changes the trials measured accumulate over this window rather than appearing all at once.
Course Plateau
A single course typically plateaus here. This is the point to reassess symptoms with your prescriber and decide whether to pause, repeat, or stop.
Section 05
Dosing Protocol
Trial dosing and practical home dosing differ, mostly in route. The pilot used intravenous dosing; the Phase 2b and home protocols use subcutaneous injection. Your RxPepsDirect physician titrates by response.
| Context | Dose | Route / Frequency | Evidence Basis |
|---|---|---|---|
| Heij Pilot Trial | 2 mg | IV, three times weekly, 4 weeks | Phase 2 Pilot |
| Culver Phase 2b Effective Dose | 4 mg | Subcutaneous, daily, 28 days | Phase 2b Primary Endpoint |
| RxPepsDirect Standard | Start 1.2 mg (20 units) | Subcutaneous, daily, titrated, 4 to 12 weeks | Clinical Practice |
| Higher Dose | 8 mg/day | Subcutaneous, daily | No Added Benefit vs 4 mg |
Context
Dose
Route / Frequency
Evidence Basis
Context
Dose
Route / Frequency
Evidence Basis
Context
Dose
Route / Frequency
Evidence Basis
Context
Dose
Route / Frequency
Evidence Basis
Subcutaneous injection into abdominal fat with a standard insulin syringe (28 to 31 gauge, 6 to 8 mm needle). Rotate sites. Timing is flexible because ARA-290 does not align with any hormonal pulse. Most patients dose in the morning for routine consistency. Note the gap between the conservative 1.2 mg starting dose RxPepsDirect uses and the 4 mg dose that moved the primary endpoint in the Phase 2b trial: your prescriber decides where to land based on your response and tolerance.
Section 06
Ready to Inject
0
Reconstitution steps required
503A
Licensed pharmacy (Optimal Balance), physician-supervised
Overnight
FedEx shipping in a reusable cooled travel case
Section 07
Safety and Side Effects
ARA-290 was well tolerated across the published trials, with no safety concerns raised on clinical or laboratory assessment. The most notable safety point is what did not happen: red cell counts did not rise, confirming the non-erythropoietic design.
| Consideration | Detail | Action |
|---|---|---|
| Injection site reaction | Mild, the most commonly noted event | Rotate sites. Let the vial warm slightly before injecting. |
| Blood disorders / EPO-pathway medications | ARA-290 is EPO-derived even though it is non-erythropoietic | Tell your prescriber so they can confirm it is appropriate for you. |
| Pregnancy / lactation | No safety data | Avoid. |
| Anti-doping tested athletes | EPO-derived molecule, uncertain status | Confirm with your governing body before use. |
Consideration
Detail
Action
Consideration
Detail
Action
Consideration
Detail
Action
Consideration
Detail
Action
Section 08
Stacking
Pairs Well With
BPC-157
Tissue repair through a different pathway. A common pairing when nerve and soft-tissue complaints overlap. Separate injection windows.
GHK-Cu
Anti-inflammatory and tissue remodeling via copper-peptide signaling. Complementary mechanism, independent timing.
Thymosin Alpha-1
Immune support alongside repair and anti-inflammation. Different systems, no timing conflict.
Avoid or Use Caution
Exogenous EPO or blood-doping agents
Redundant and risky pathway overlap. The point of ARA-290 is to repair without erythropoiesis. Combining it with EPO defeats that and adds clotting risk.
Pregnancy / lactation
No safety data. Avoid.
Section 09
Pricing
Pharmacy: Medication
$80 per 30 mg vial. Compounded and shipped by Optimal Balance Pharmacy, a 503A licensed compounding pharmacy. Pre-reconstituted at 6 mg/mL, FedEx overnight.
Medical Service: Physician Consultation
$39 medical visit fee. Intake consultation including symptom review, protocol design, prescription writing, and follow-up. Billed by RxPepsDirect for the medical service only.
Section 10
Legal Access in 28 States
503A Licensed Pharmacy
Optimal Balance Pharmacy, U.S. licensed
Physician Prescription Required
Compounded medication, Rx only
Investigational Compound
Phase 2 evidence, no FDA approval
Off-Label, Legal Practice
Standard and legal in U.S. medicine
ARA-290 is an investigational peptide. It reached Phase 2 trials but was never FDA-approved for any indication. In the United States it is available through 503A patient-specific compounding under a physician prescription. The 503A pathway is the documented legal route for compounded peptide access. RxPepsDirect prescribers serve patients in 28 states.
Section 11
Community Q&A
Does ARA-290 raise my red blood cell count like EPO?
No. It was engineered from erythropoietin to activate only the innate repair receptor and not the receptor that makes red cells. In the trials, hematocrit and hemoglobin did not rise. That non-erythropoietic profile is the entire reason the molecule exists.
Is the evidence actually strong?
It is Phase 2, not established. A 22-patient pilot and a 64-patient Phase 2b, almost all in sarcoidosis nerve pain, mostly sponsor-run. The nerve-repair markers improved, but pain improved in the placebo group too, so the symptom benefit is less certain than the biology. No Phase 3, no FDA approval.
Will I feel anything?
Probably not directly. ARA-290 works on cellular repair and inflammation, not on receptors that produce a felt effect. Any benefit shows up as gradual symptom change over weeks, not as a sensation after a dose.
Can athletes use it?
It is non-erythropoietic, so it is not a classic blood-doping agent. But it is EPO-derived and engages an EPO-receptor- containing complex, an area anti-doping programs watch closely. Confirm its status with your governing body before use.
How long is a course?
The trials ran about 28 days. RxPepsDirect courses run 4 to 12 weeks, with your prescriber reassessing before any extension or repeat.
Section 12
The RxPepsDirect Model
Pharmacy: Optimal Balance, 503A Licensed
Optimal Balance Pharmacy compounds your ARA-290 under a patient-specific prescription, USP <797> sterile standards, and federal 503A oversight.
Medical Service: RxPepsDirect Physicians
A licensed physician reviews your history, screens for contraindications, designs your titration, and writes your prescription. RxPepsDirect bills the $39 medical visit fee for this service.
Transparent Safety Communication
This guide flags that the human evidence is Phase 2 only, that the Phase 2b pain endpoint had a large placebo response, that there is no FDA approval, and that general recovery use is extrapolation. We do not hide limitations to make a sale.
Legal Access in 28 States
Every shipment is a compounded prescription medication filled by a 503A licensed pharmacy under a physician prescription.
References
- Brines M, Patel NS, Villa P, et al. Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin. Proc Natl Acad Sci U S A. 2008. PMID: 18676614
- Heij L, Niesters M, Swartjes M, 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. PMID: 23168581
- 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. Invest Ophthalmol Vis Sci. 2017. PMID: 28475703
- van Velzen M, Heij L, Niesters M, et al. ARA 290 for treatment of small fiber neuropathy in sarcoidosis. Expert Opin Investig Drugs. 2014. PMID: 24555851
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