ARA-290 (Cibinetide)

What is ARA-290, and how does it differ from EPO?

EPO is a hormone produced in the kidney that stimulates red blood cell production in bone marrow; it is also produced locally in many tissues and plays a protective role against injury. According to the foundational study published in 2008, these two functions run through different receptors: blood cell production through a structure made of two copies of the EPO receptor, and tissue protection through a complex made of the EPO receptor and CD131 (β-common receptor). The researchers designed an 11-amino-acid peptide that mimics the water-facing surface of the part of EPO called the B helix. ^[1] This peptide was later developed under the name ARA 290, and its international name became cibinetide. ^[8]

In the same study, the peptide showed protective effects in rodent models of ischemic stroke and kidney ischemia-reperfusion injury, accelerated wound healing, and improved cognitive function; it did not stimulate blood cell production in cell and animal experiments. ^[1] These findings have not been confirmed in humans. Some of the study’s authors were, during the research, employees of a company developing EPO analogs and tissue-protective compounds. ^[1]

According to the EMA orphan designation summary, the substance binds to and activates this structure called the “innate repair receptor” (IRR); the receptor is expected to suppress inflammation-related cytokine production and support repair of damaged cells. ^[8] This is a hypothesized mechanism of action; it does not mean clinical benefit in patients.

What did the small fiber neuropathy studies in sarcoidosis show?

Sarcoidosis is a disease that proceeds with inflammatory foci called granulomas in many organs of the body. When it affects the nervous system, nerve pain, hypersensitivity to heat and cold, numbness, and tingling can occur. ^[8] Loss of thin (small) nerve fibers is associated with pain and autonomic symptoms in these patients, and standard treatments often fall short. ^[3]

ARA-290 was tested in this area in two small studies from Leiden University Medical Center in the Netherlands and in a phase 2b study whose authors came from institutions in the USA, the Netherlands, the UK, and Qatar. In all three studies, employees of the developer company are among the authors; in the two Leiden studies, these authors also declared company shares or stock options. The pilot study was initiated by investigators, and the drug was supplied by the company. ^{[2] [3] [5]}

SFNSL (small fiber neuropathy screening list) is a scale that collects patient-reported autonomic and pain symptoms. In the Dahan study, an improvement of at least two points was seen in 81% of patients in the ARA-290 group and 47% in the placebo group; the 6-minute walk distance increased by an average of 18.7 meters in the ARA-290 group, while it fell by 15.1 meters in the placebo group (p=0.049). ^[3] The “pain interaction” score, which measures the effect of pain on daily life, also improved more in the ARA-290 group. However, pain intensity itself decreased to the same extent in both groups. ^[3] The authors list the main limitations of the study as the inclusion of only patients with pain and the absence of patients known to have active sarcoidosis in other organs. ^[3]

This picture shows a consistent signal on symptom scales but no advantage over placebo on pain intensity, one of the outcomes that matters most to patients. The marked improvement in the placebo groups as well is a reminder that in short, small studies, expectation effects can strongly influence results.

Corneal nerve fibers: what does a surrogate measure tell?

In the cornea, the transparent layer of the eye, thin nerve fibers can be counted with a special microscope; this measurement is used as an indicator of small fiber loss. In the Dahan study, corneal nerve fiber area in the ARA-290 group rose by a median of 14.5% from baseline (p=0.022; within-group comparison), while a non-significant decrease was seen in the placebo group. ^[3] In a correction published in 2016, the journal explained that there was an arithmetic error in the corneal nerve fiber area algorithm of this paper and that the reported absolute values were smaller than they should have been. ^[4]

In the phase 2b study, this measure was the primary outcome. At day 28, the placebo-adjusted mean increase in the three dose groups was 109 (95% CI −429 to 647), 697 (159 to 1,236; P=0.012), and 431 µm² (−130 to 992), respectively: only the middle dose was significant, and the highest dose was not. An increase in regenerated nerve fibers in the skin was reported in the middle-dose group (P=0.035). ^[5] The authors argue that corneal fiber area can be used as a surrogate measure for evaluating disease-modifying treatments. ^[5] However, a change in a surrogate measure does not mean lasting benefit in pain or quality of life; the fact that the effect did not increase with dose also complicates interpretation.

Type 2 diabetes and eye studies

Type 2 diabetes and painful neuropathy. The phase 2 study published in 2015 enrolled 49 patients with type 2 diabetes and painful neuropathy; one participant was withdrawn on day 15 because of worsening kidney function, and the analysis was done with 48 people. Participants received ARA-290 or placebo for 28 days and were followed for one more month. ^[6] In the 42 people with complete HbA1c measurements, the mean change at day 56 was −0.21 percentage points in the ARA-290 group and +0.21 in the placebo group (p=0.002). ^[6] The PainDetect score, which measures neuropathic symptoms, improved more in the ARA-290 group than with placebo (p=0.037). The increase in corneal nerve fiber density was not significant in the whole group; a significant increase was seen only in the subgroup with markedly low baseline density, in 18 people in the ARA-290 arm (the change in 19 placebo patients in the same subgroup was not significant). ^[6] The authors state the short treatment duration and the generally good glucose control of participants as the two main limitations of the study; three authors are executives and shareholders of the developer company. ^[6]

Diabetic macular edema. The phase 2 study in Northern Ireland, which had no control group, enrolled 9 patients, and 8 completed the 12-week treatment. No average improvement was seen in visual acuity, retinal thickness, retinal sensitivity, or tear production; only a small improvement in a visual function questionnaire was reported. No serious side effects or antibodies against cibinetide were seen. Five authors are linked to the developer company: four are executives and shareholders, and one is a clinical development consultant. ^[7] On ClinicalTrials.gov, the record of this study has the status “terminated.” ^[9]

Safety: what is known and unknown?

The five clinical studies summarized on this page include about 180 participants in total (22, 38, 64, 48, and 9 people), and treatment durations are 4–12 weeks; long-term safety is unknown. The reported findings are:

• Sarcoidosis studies: In the pilot study, no safety problem was found in clinical or laboratory assessments. ^[2] In the 38-person study, no serious side effects were seen during dosing and 12 weeks of follow-up; in the ARA-290 group, a 14 kg weight loss in one patient, found to have begun before the study, was recorded as a moderate adverse event. ^[3]
• Diabetes study: Four serious adverse events were reported in the ARA-290 arm; the investigators considered two “possibly related” to the drug. One of these was a slight worsening of previously borderline kidney function in a participant whose diuretic dose had been increased, and the drug was stopped in this participant. In addition, a 70-year-old participant was hospitalized with severe cellulitis two weeks after the last dose and had a fatal heart attack; the safety committee judged this event unrelated to the drug. ^[6]
• Unknowns: There are no data on pregnancy, breastfeeding, children, long-term use, or the content of products made outside clinical studies. Purity, sterility, and label accuracy are a general problem in unlicensed peptide products: Peptide side effects.

Licensing and development status of ARA-290

The European Commission granted cibinetide orphan designation for the treatment of sarcoidosis on October 7, 2013. According to the EMA summary, at the time of designation no medicine was authorized for sarcoidosis anywhere in the EU; in the US, orphan designation had also been granted for treatment of neuropathic pain related to sarcoidosis. EMA stresses that orphan designation is not a marketing authorization and that quality, safety, and efficacy must be demonstrated separately; the designation page is “positive” as of 2026 and is to be reassessed when a marketing authorization is granted. ^[8]

A “cibinetide” search on ClinicalTrials.gov shows four registered studies: a 36-person phase 1/2 cognitive effect study, the 64-person sarcoidosis phase 2b study, a 24-person prediabetes/type 2 diabetes phase 2 study whose status is “unknown,” and the macular edema study terminated with 9 people. The latest end date is August 2017. ^[9] No phase 3 study is among these records.

Is ARA-290 prohibited in sport?

The WADA 2026 Prohibited List names “innate repair receptor agonists” in item S2.1.5, under the heading S2.1 “erythropoietins and agents affecting erythropoiesis”; asialo EPO and carbamylated EPO are given as examples, and other substances with similar chemical structure or similar biological effect are also covered. Substances in this class are prohibited at all times, in and out of competition. ^[11] ARA-290 is not named in the list; however, clinical publications describe the substance as a peptide designed to activate the innate repair receptor. ^{[2] [5]} A doping research laboratory in Germany selected ARA-290 as a model compound among peptides “prohibited in sport,” incubated the substance with blood samples in the laboratory, and identified the main breakdown product. ^[10]

What is the status of ARA-290 in Türkiye?

A guide covering the legal status of peptides in general: Are peptides legal? The meaning of the “for research purposes” label: What does research peptide mean?

Evidence table: claim, population, and limits

Limits of this guide

This page summarizes published studies and official documents on ARA-290 (cibinetide). It contains no individualized dose, preparation, method of administration, cycle length, or product source. No approved ARA-290 product exists for use outside clinical studies. Regulatory status may change; the information on this page is valid as of October 2026.