What it is
ARA290, also called cibinetide, is a lab-made chain of 11 amino acids. It was copied from one small patch on the surface of erythropoietin (EPO), the hormone that tells bone marrow to make red blood cells. Besides that job, EPO also seems to protect tissues from injury and inflammation, but giving EPO itself raises red-cell counts and blood-clot risk.
The idea behind ARA290 was to keep the protective signal and drop the blood-making one. It is designed to act on a different receptor from the one that drives red-cell production. It has been tested in small studies in people with nerve damage linked to sarcoidosis, an inflammatory disease, and in diabetes. No medicine containing it is approved.
Cibinetide (pHBSP, pyroglutamate helix B surface peptide) is pGlu-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser (C51H84N16O21, 1257.3 g/mol). It reproduces the adjacent residues that form the aqueous face of helix B of EPO (residues 58–82 in the parent protein), the surface that does not contact the classical receptor when EPO binds it.
EPO drives erythropoiesis through an EPO receptor homodimer, whereas its tissue-protective actions have been attributed to a heterocomplex of the EPO receptor and CD131, the beta-common receptor, termed the innate repair receptor. Cibinetide was designed to activate this heterocomplex selectively; Brines et al. (2008) reported that it was not erythropoietic in vitro or in vivo. The developers describe the downstream effects as anti-inflammatory and tissue-protective, based on preclinical models of ischaemic and nerve injury.
Pharmacokinetics: Brines et al. (2008) reported a plasma half-life of about 2 minutes in rats and rabbits, and Lois et al. (2020) cite a peak concentration of about 1.8 nM after a 4 mg subcutaneous dose in non-obese subjects. A human half-life has not been published in the sources reviewed for this article. Its sustained effects are attributed by the developers to downstream signalling rather than persistent exposure; that interpretation has not been independently tested.
Who made it and when
ARA290 comes from the laboratory of Michael Brines and Anthony Cerami in New York State. Brines and Cerami had spent years studying how EPO protects the brain, heart and nerves. In 2008 they published a set of short peptides that mimic the protective face of EPO, including the 11-amino-acid version later named ARA290.
Their company, first Warren Pharmaceuticals and later Araim Pharmaceuticals, ran human studies with academic partners in the Netherlands, Sweden, the United States and Northern Ireland between about 2012 and 2017. According to the developer, the FDA gave the peptide orphan-drug status for sarcoidosis, and the European Union did the same in 2013; that status offers incentives for rare-disease research. No new trial has started since 2016.
Brines et al. (PNAS 2008), working at Warren Pharmaceuticals in Ossining, New York, reported that an 11-residue peptide simulating the aqueous face of EPO helix B was tissue-protective and non-erythropoietic in rodents. Development continued at Araim Pharmaceuticals (Ossining, later Tarrytown, New York), assignee of US 9,580,465 (priority 2008), whose claims cover treating tissue damage with the pyroglutamate peptide; Google Patents lists that patent as expired for unpaid maintenance fees.
Clinical work was largely conducted with Albert Dahan’s group at Leiden University Medical Center, with further studies at the Cleveland Clinic, the Karolinska Institutet and the Belfast Health and Social Care Trust. Araim announced US orphan and Fast Track designations for neuropathic pain in sarcoidosis and, in July 2016, a US orphan designation for sarcoidosis; the EU orphan designation for sarcoidosis (EU/3/13/1191) dates from 2013-10-07. The most recent interventional study, a Belfast trial in diabetic macular oedema, started in April 2016 and was terminated in 2017 when the study drug expired. The latest Araim activity that could be verified is regulatory housekeeping: EMA records the transfer of the EU designation to an Irish Araim entity in April 2019. No clinical development after 2017 could be verified.
What the data say
The human evidence comes from a handful of small, short trials, most run with the developer. In people with sarcoidosis who had painful damage to small nerve fibres, four weeks of daily injections increased the amount of nerve fibre seen in the cornea of the eye, which researchers use as a window on small-nerve health. That effect was clear only at the middle dose. Pain improved in every group, including placebo, so the pain result was not a clear difference.
A small diabetes study reported better blood-sugar control and fewer nerve-pain symptoms. An eye study in diabetic macular swelling found no average improvement. No large confirmatory trial has been done, and none is registered.
Animal data (Brines et al., 2008): the 11-residue peptide was protective in rodent ischaemic stroke and renal ischaemia-reperfusion models and accelerated wound healing, without erythropoiesis; a longer helix B peptide was also protective in retinal-oedema and nerve-trauma models.
Sarcoidosis: Dahan et al. (Mol Med 2013) reported that 28 days of daily subcutaneous ARA 290 in a blinded, placebo-controlled trial improved neuropathic symptoms, corneal nerve fiber density and 6-minute walk distance. The Phase 2b NCT02039687 (n=64; 1, 4 or 8 mg/day subcutaneously for 28 days) met its primary endpoint only at 4 mg: placebo-corrected change in corneal nerve fiber area was 109, 697 (p = 0.012) and 431 µm² for the three doses. GAP-43-positive intraepidermal fibres increased at 4 mg (p = 0.035). Pain improved in all arms; at 4 mg the placebo-corrected reduction in the moderate-to-severe pain subgroup was not significant (p = 0.157).
Type 2 diabetes: Brines et al. (Mol Med 2015; placebo-controlled Phase 2, 4 mg subcutaneously daily for 28 days) reported improved HbA1c, lipids and PainDetect scores, with no safety issues identified. Diabetic macular oedema: open-label, n=9, 4 mg daily for 12 weeks, mean visual acuity −2.9 letters and retinal thickness +10 µm (Lois et al., 2020).
Regulatory picture
Three separate facts. Approval: no medicine containing ARA290 is approved by the FDA or any other regulator, and no marketing application is known to have been filed. The orphan-drug status it received is an incentive for developers, not an approval. Compounding: ARA290 was nominated for the FDA’s list of ingredients that compounding pharmacies may use, but the FDA put it in “Category 3”, meaning the nomination did not include enough information to evaluate. That is not a safety finding and not permission; it simply was never assessed. Enforcement: no FDA warning letters naming ARA290 were found. No clinical development after 2017 could be confirmed.
Approval: none. No NDA submission is known. FDA orphan designations (sarcoidosis-associated neuropathic pain, and sarcoidosis, 2016) and Fast Track status were announced by the developer, and the EU orphan designation is recorded by EMA; orphan designation carries incentives but no marketing authorisation. No trial has started since 2016 and no active IND-stage programme could be verified, so this article records approval as none.
Compounding: cibinetide (ARA-290) was placed in Category 3 of FDA’s 503A nominations list on 2023-09-29, “bulk drug substances nominated without adequate support”, and remained there in the list updated 2026-05-14. It is not on the 503A bulks list in 21 CFR 216.23, not in Category 1 (under evaluation) and not in Category 2 (significant safety risks). FDA’s interim policy extends enforcement discretion to Category 1 substances only. This article records compounding status as unknown because the site’s categories do not include Category 3.
