What it is
ARA290 is also called cibinetide. It is a short chain of 11 amino acids (a peptide) made in a lab. It copies one small patch on the surface of a hormone called erythropoietin (EPO). EPO tells the bone marrow to make red blood cells.
EPO also seems to protect body tissues from injury and swelling. But giving EPO itself raises red blood cell counts. It also raises the risk of blood clots.
ARA290 was made to keep the protective effect and drop the blood-making one. It is designed to work through a different receptor (a docking spot on cells). This is not the one that makes red blood cells. It has been tested in small studies. These included people with nerve damage linked to sarcoidosis, an inflammatory disease. They also included people with 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 came from the lab of Michael Brines and Anthony Cerami in New York State. They had studied for years how EPO protects the brain, heart and nerves. In 2008 they published a set of short peptides that copy the protective side of EPO. One of them was the 11-amino-acid version later named ARA290.
Their company was first called Warren Pharmaceuticals and later Araim Pharmaceuticals. It ran human studies with university partners between about 2012 and 2017. These were in the Netherlands, Sweden, the United States and Northern Ireland.
The company says the FDA gave ARA290 orphan-drug status for sarcoidosis. It says the European Union did the same in 2013. This status gives rewards for research on rare diseases. It is not an approval. 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 few small, short trials. The drug’s maker helped run most of them.
One group had sarcoidosis and painful damage to small nerve fibres. They got daily shots for four weeks. The shots increased the amount of nerve fibre seen in the cornea (the clear front of the eye). Researchers use the cornea as a window on small-nerve health. This effect was clear only at the middle dose. Pain got better in every group, including the group given a dummy treatment (placebo). So the drug did not clearly beat the dummy for pain.
A small diabetes study reported better blood sugar control. It also reported fewer nerve pain symptoms. An eye study looked at people with diabetes-related swelling at the back of the eye. It found no average improvement. No large trial has been done to confirm any of this. None is listed in the trial registry.
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
There are three separate points.
Approval: The FDA has not approved any medicine containing ARA290. No other regulator has either. No request to sell it is known to have been filed. The orphan-drug status it got is a reward for developers, not an approval.
Compounding: Compounding pharmacies mix their own medicines. Someone asked the FDA to add ARA290 to the list of ingredients these pharmacies may use. The FDA put it in “Category 3”. This means the request did not include enough information to judge it. It is not a safety finding. It is not permission. It was simply never assessed.
Enforcement: No FDA warning letters naming ARA290 were found. No testing in people 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.
