ARA290 (Cibinetide)

Origin and structure

ARA-290 is a synthetic chain of 11 amino acids: pyroglutamate, Glu, Gln, Leu, Glu, Arg, Ala, Leu, Asn, Ser, Ser. It mimics the outward-facing surface of helix B, one of the helices that make up erythropoietin (EPO), the kidney hormone that drives red-blood-cell production. In the literature it also appears as pHBSP (pyroglutamate helix B surface peptide) and ARA 290; cibinetide is its official name.

The peptide was described in 2008 by a group led by Michael Brines and Anthony Cerami, building on the finding that EPO protects tissue through a different receptor from the one that makes red blood cells. Their paper showed that helix B on its own, and then the 11-amino-acid peptide, protected tissue in rodent models of stroke and kidney injury without stimulating red-cell production. Brines and Cerami took it into human trials through Araim Pharmaceuticals in New York, where both worked; most of those trials were run with the anaesthesiology department of Leiden University Medical Center.

How it is thought to work

EPO acts through two different receptors. Red-cell production runs through a pair of EPO receptors (a homodimer). Tissue protection is attributed to a second complex, the innate repair receptor, in which the EPO receptor pairs with CD131, the beta-common receptor. According to the developers, this complex is largely absent from healthy tissue and appears where tissue is injured, inflamed or under metabolic stress, where it damps inflammatory signalling and supports repair.

ARA-290 was designed to activate only the second receptor. It did not stimulate red-cell production in cell or animal tests, and in the trials that reported laboratory results, blood counts and blood chemistry did not change in a clinically relevant way.

The peptide is short-lived. In healthy volunteers, an injection under the skin at the dose later used in the trials gave a peak blood level of about 3 ng/mL and a terminal half-life of about 20 minutes. Some effects in the trials nevertheless outlasted the dosing: in the type 2 diabetes trial, HbA1c was still lower a month after the last injection. The developers explain this as a brief signal switching on longer-lasting repair processes; that explanation comes from their own research.

Is ARA-290 approved?

No. Cibinetide has no marketing authorisation from the EMA, the FDA or any other regulator, so there is no approved dose, label or product information. What it does have are orphan designations, a status for medicines in development for rare conditions that the EMA states plainly is not a marketing authorisation. The position by region:

• EU: orphan designation for the treatment of sarcoidosis on 7 October 2013 (EU/3/13/1191) and for the prevention of graft loss after pancreatic islet transplantation on 29 August 2016 (EU/3/16/1721). Both have been held since April 2019 by Araim Pharmaceuticals Europe in Ireland and are still on the EMA register.
• US: orphan designations for neuropathic pain due to sarcoidosis and for the prevention of delayed graft function after kidney transplantation, as recorded in the EMA's summaries. In the FDA's list of substances nominated for pharmacy compounding, updated on 14 May 2026, cibinetide sits in Category 3, nominated without adequate support, so US pharmacies may not compound it under section 503A.
• Netherlands: not a registered medicine, and it may not be sold or promoted for human use. It is only available as research material, which is the basis our shop operates on.
• Sport: prohibited at all times. The WADA list does not name ARA-290, but section S2.1.5 bans innate repair receptor agonists, with asialo EPO and carbamylated EPO as examples, and the S2 class expressly covers substances with a similar biological effect.
• Trials: ClinicalTrials.gov lists no phase 3 study. The most recent published trial recruited its patients in 2016 and 2017.

What the research shows

Behind the human work sits a larger body of animal research. The 2008 paper that introduced the peptide reported protection in rodent models of stroke and of kidney damage after interrupted blood flow, faster wound healing and better performance on cognitive tests. Those uses have so far been studied only in animals.

Six human trials have been published. All were small and short: four of the patient trials gave the peptide for four weeks, none for longer than 12 weeks, and the largest had about 16 patients per group. Five were double-blind and placebo-controlled, five involved Leiden University Medical Center, and staff of the developer co-authored five. The positive findings rest mostly on questionnaires and on corneal nerve fibres counted under a microscope, a surrogate marker rather than an outcome patients notice, and in all three sarcoidosis trials pain intensity improved no more than on placebo. No trial has been large or long enough to show whether ARA-290 changes the course of neuropathy. In order of publication:

• Sarcoidosis pilot (Heij, 2012): 22 patients with small-fibre neuropathy received ARA-290 intravenously or placebo for four weeks. A neuropathy symptom score (SFNSL) improved by 11.5 points against 2.9 on placebo; pain scores improved equally in both groups.
• Sarcoidosis, 28 days (Dahan, 2013): 38 patients, daily injections or placebo. Corneal nerve fibre area increased, while skin biopsies showed no clear change in nerve fibre density. Symptom scores and the extent to which pain interfered with daily life improved more on ARA-290, and 6-minute walking distance rose by 18.7 m against a fall of 15.1 m on placebo. Pain intensity again improved equally in both groups.
• Type 2 diabetes (Brines, 2015): 49 people with painful neuropathy, daily injections or placebo for 28 days, 48 analysed. From a well-controlled start of about 7%, HbA1c had fallen by 0.21 percentage points at day 56 against a rise of 0.21 on placebo, and neuropathic symptoms on the PainDetect questionnaire improved in the ARA-290 group. Corneal nerve density rose only in a post-hoc subgroup with the lowest starting values.
• Healthy volunteers (Cerit, 2015): 36 people received a single dose or placebo and were tested a week later on emotional processing, as a model of antidepressant action. The effects were mixed, mood did not change, and the authors concluded the results did not clearly support an antidepressant-like profile.
• Phase 2b, sarcoidosis (Culver, 2017): 64 patients, one of three doses or placebo for 28 days. Only the middle dose met the primary endpoint, a placebo-corrected increase in corneal nerve fibre area of 697 µm² (95% CI 159 to 1,236); the lowest and highest doses did not. Pain improved in every group, placebo included.
• Diabetic macular oedema (Lois, 2020): 9 patients, no control group, daily injections for 12 weeks; 8 completed. Visual acuity and retinal thickness did not improve; scores on a visual-function questionnaire did.

ARA-290 versus EPO

EPO itself protects tissue in animal models, but as a medicine it is hard to use for that purpose: it raises red-cell mass and activates blood-vessel walls and platelets, which together raise the risk of thrombosis. ARA-290 was built to separate the two actions, keeping the tissue-protective signal and dropping the effect on red cells. The trials support the second half of that claim; the first half, protection or repair in patients, rests on small phase 2 studies.

For anti-doping the separation makes no difference: WADA lists EPO, EPO mimetics and innate repair receptor agonists side by side under S2.1, and all of them are prohibited at all times. Nor is ARA-290 a weaker form of EPO: it has no role in treating anaemia.

Side effects and safety

The safety data come from the six trials, in which no one received ARA-290 for longer than 12 weeks. The fullest record is the 64-patient phase 2b trial, whose adverse events are posted on ClinicalTrials.gov: headache was reported by 8 of 46 participants on cibinetide and none of 16 on placebo, and nausea by 5 of 46 against none. Injection-site pain was more frequent on placebo (4 of 16) than on cibinetide (3 of 46). Three participants on cibinetide had a serious adverse event, one of them suicidal ideation in the highest-dose group; none on placebo did.

In the type 2 diabetes trial, the number of mild and moderate adverse events was similar in both groups, but four serious adverse events occurred in the ARA-290 group, two of them judged possibly related. In one participant whose diuretic dose had been raised, existing kidney impairment worsened and dosing was stopped; another developed severe cellulitis two weeks after the last dose and had a fatal heart attack, which the safety committee judged unrelated to the peptide.

In the trials that reported laboratory results, blood counts and blood chemistry did not change in a clinically relevant way, and no antibodies against the peptide were found in the diabetes and macular oedema trials. Long-term safety has not been studied.

Frequently asked questions

Is ARA-290 legal in the Netherlands?

It is not a registered medicine and may not be sold or promoted for human use. It can be bought and sold as research material, which is the basis for our shop. The orphan designations do not change that: they are a development status, not an authorisation. Our guide on research-use-only products in the Netherlands explains what that status means.

Does ARA-290 raise haemoglobin like EPO?

No. It was designed to bypass the receptor pair that drives red-cell production, it did not stimulate red-cell production in animal tests, and blood counts did not change in a clinically relevant way in the trials that measured them. For the same reason it has no role in treating anaemia.

Is ARA-290 banned in sport?

Yes, at all times, in and out of competition. The WADA list does not name it, but it prohibits innate repair receptor agonists under S2.1.5, in the same section as EPO, and the S2 class covers substances with a similar biological effect. ARA-290 was designed as exactly such an agonist. See our guide on peptides and the doping list.

Is ARA-290 still being developed?

There are no visible signs of it. ClinicalTrials.gov lists no phase 3 study, the most recent published trial recruited its patients in 2016 and 2017, and in May 2026 the FDA listed cibinetide among substances nominated for compounding without adequate support. The EU orphan designations are still on the register, but they say nothing about current activity.

How long does ARA-290 stay in the body?

Briefly. In healthy volunteers, an injection under the skin gave a terminal half-life of about 20 minutes. Some trial effects lasted weeks longer, which the developers attribute to the receptor switching on longer-lasting repair processes; that explanation comes from their own research.

Storage and handling

Store according to product-label instructions and batch handling notes. Lyophilized research peptides are commonly kept dry, protected from light, and handled with clean laboratory technique.

References

Checked against these sources on 28 October 2026.