ARA-290

What it is

ARA-290 is a synthetic peptide derived from erythropoietin biology but designed not to reproduce erythropoietin’s red-blood-cell-stimulating activity^{[6 ]}. The compound is also called cibinetide and pHBSP, short for pyroglutamate helix B surface peptide^{[6 –7 ]}. It was engineered to activate tissue-protective signaling proposed to occur through an erythropoietin receptor and beta-common receptor complex sometimes called the innate repair receptor^{[6 ]}.

The core idea is receptor selectivity. Classical erythropoietin stimulates erythropoiesis through EPOR homodimer signaling. ARA-290 was designed from the helix B surface of erythropoietin to target tissue-protective or repair pathways without stimulating red-cell production through the erythropoietic receptor^{[6 ]}. This distinction is central to the drug-development rationale, although aspects of the innate repair receptor model remain scientifically debated^{[6 ,15 ]}.

ARA-290 has been studied most visibly in small fiber neuropathy associated with sarcoidosis and type 2 diabetes^{[8 –11 ]}. Outcomes in these studies included symptom measures, corneal nerve fiber imaging, skin nerve fiber measures, and metabolic parameters^{[8 –11 ]}. The compound has also been investigated in preclinical models of renal ischemia-reperfusion injury, inflammatory disease, ocular ischemia, lupus-like disease, and other tissue-injury contexts^{[12 –16 ]}.

ARA-290 is typically described in clinical trials as administered intravenously or subcutaneously, depending on the study^{[8 –11 ]}. This page describes published research and regulatory status only. It does not provide dosing guidance or endorse use outside clinical trials.

The name cibinetide is important because some regulatory documents use that term rather than ARA-290. FDA’s 503A category list uses “Cibinetide (ARA-290),” while EMA’s orphan designation page uses cibinetide and lists the active substance sequence^{[2 ,7 ]}. Readers searching regulatory databases should use both names.

Regulatory status

ARA-290/cibinetide is not FDA-approved for sarcoidosis, small fiber neuropathy, diabetic neuropathy, pain, autoimmune disease, tissue repair, or any other indication in the United States.

503A Category 3

FDA’s April 22, 2026 503A category list includes “Cibinetide (ARA-290)” in Category 3, which FDA describes as bulk drug substances nominated without adequate support^{[2 ]}. Category 3 status does not mean FDA has approved the substance for compounding; it means the nomination lacks adequate support for the category-list process^{[1 –2 ]}.

Under FDA’s 503A framework, state-licensed pharmacies and physicians compounding from bulk substances must use substances that meet an applicable USP/NF monograph pathway, are components of FDA-approved drug products when no monograph exists, or appear on FDA’s 503A bulks list^{[1 ]}. ARA-290 was not identified as a current 503A bulks-list substance or Category 1 interim-policy substance during this review^{[1 –2 ]}.

503B outsourcing facilities

Under FDA’s 503B framework, outsourcing facilities generally may use a bulk drug substance only if it appears on the 503B bulks list or the compounded drug appears on FDA’s shortage list at the relevant time^{[3 ]}. No FDA-compliant routine 503B pathway for ARA-290 was identified in the sources reviewed, including FDA’s 503B bulk-substances list^{[4 ]}.

EMA orphan designation

Internationally, EMA granted orphan designation EU/3/13/1191 in 2013 for cibinetide for treatment of sarcoidosis, and the EMA page states that orphan designation is not a marketing authorization^{[7 ]}. The EMA page also notes that orphan designation had been granted in the United States for neuropathic pain due to sarcoidosis^{[7 ]}. Orphan or fast-track status should not be confused with approval.

ARA-290 is not listed in federal controlled-substance schedules in 21 CFR Part 1308 as reviewed on May 7, 2026^{[5 ]}. Date of last regulatory verification: May 7, 2026.

Research summary

The mechanistic rationale was summarized by Collino and colleagues in a 2015 review, which described ARA-290 as an 11-amino-acid peptide modeled from the helix B surface of erythropoietin and designed to activate the innate repair receptor without erythropoietic activity^{[6 ]}. The review describes a short plasma half-life but potentially longer-lasting downstream biological effects in preclinical models and clinical studies^{[6 ]}.

Sarcoidosis small fiber neuropathy — Heij 2012, Dahan 2013, Culver 2017

Sarcoidosis-associated small fiber neuropathy is the most clinically developed area. Heij and colleagues conducted a randomized, double-blind pilot study in 22 patients with sarcoidosis and symptoms of small fiber neuropathy, using intravenous ARA-290 or placebo for four weeks^{[8 ]}. The study reported improvement in small fiber neuropathy symptom scores and no drug-related serious safety signal in that small sample^{[8 ]}.

Dahan and colleagues later reported a blinded placebo-controlled trial of daily subcutaneous ARA-290 for 28 days in sarcoidosis-associated small nerve fiber loss^{[9 ]}. The study reported improved neuropathic symptoms, increased corneal small nerve fiber density, changes in temperature sensitivity, and increased six-minute walk distance^{[9 ]}. Culver and colleagues later focused on corneal nerve fiber abundance in patients with sarcoidosis-associated small fiber loss and neuropathic pain^{[10 ]}.

Type 2 diabetes — Brines 2015

Type 2 diabetes has also been studied. Brines and colleagues reported that ARA-290 improved metabolic control and neuropathic symptoms in patients with type 2 diabetes^{[11 ]}. This paper is relevant because it moves beyond sarcoidosis, but it remains a limited clinical study rather than an approval-enabling evidence base.

Preclinical tissue-protection models

Preclinical tissue-protection research includes renal ischemia-reperfusion injury, endothelial progenitor-cell function, inflammatory bowel disease models, lupus-like disease, and ocular ischemia models^{[12 –14 ,16 ]}. These studies support broad biological interest but do not establish human efficacy for those conditions.

Calibration

The neuropathy studies used outcomes that are clinically meaningful but not necessarily sufficient for approval on their own. Symptom scores, corneal confocal microscopy measures, temperature sensitivity, walk distance, and metabolic markers can support biological plausibility, but larger trials would be needed to define patient selection, durability of effect, clinically important difference, adverse-event frequency, and risk-benefit balance^{[8 –11 ]}.

There is also mechanistic debate. ARA-290 development is based on the concept that a nonerythropoietic EPO-derived peptide can activate tissue-protective pathways without classic erythropoietic signaling^{[6 ]}. However, later commentary has questioned aspects of the proposed erythropoietin receptor and beta-common receptor interaction model^{[15 ]}. The existence of debate does not negate the clinical findings, but it does mean mechanism claims should be written as proposed rather than settled.

The regulatory record is consistent with an investigational posture. EMA orphan designation recognized sarcoidosis as a rare disease context for cibinetide development, but the EMA page explicitly separates orphan designation from marketing authorization^{[7 ]}. FDA’s Category 3 compounding listing likewise reflects inadequate support for a nomination rather than an approval or a full clinical assessment^{[1 –2 ]}. These two regulatory facts should be visible near any discussion of early human trial signals.

Evidence quality is therefore intermediate: stronger than purely animal-only peptides because several human clinical studies exist, but still investigational because no FDA-approved product or large confirmatory trial was identified. The most defensible claims are that ARA-290 has been studied in small fiber neuropathy associated with sarcoidosis and diabetes, and that early trials reported signals on symptoms and nerve-fiber measures^{[8 –11 ]}. It should not be described as an approved nerve-repair treatment.

Public discourse

European Medicines Agency Committee for Orphan Medicinal Products described cibinetide’s orphan designation for sarcoidosis and explained that the medicine remained investigational^{[7 ]}.

Albert Dahan, MD, PhD, and colleagues reported clinical and corneal nerve-fiber findings in sarcoidosis-associated small fiber neuropathy^{[9 ]}.

Culver, Dahan, and colleagues reported corneal nerve fiber abundance findings in a sarcoidosis neuropathy cohort^{[10 ]}.

Public discourse reflects the views of the speakers cited and does not represent medical advice or the editorial position of ProPeptideGuide.

Side effects and safety

ARA-290 has no FDA-approved prescribing information, so there is no FDA-reviewed adverse-reaction table, contraindication list, drug-interaction section, pregnancy/lactation language, or long-term postmarketing safety dataset.

Trial-reported tolerability

Small clinical studies in sarcoidosis-associated small fiber neuropathy reported short-term tolerability, but those studies were small and not powered to detect rare or long-latency adverse events^{[8 –10 ]}. Type 2 diabetes research was also limited in size and duration^{[11 ]}.

Mechanism-based concerns

Mechanistic safety questions include immune modulation, tissue-repair signaling, receptor specificity, and the broader implications of erythropoietin-derived biology. ARA-290 was designed to avoid erythropoiesis, but that design goal does not by itself establish safety across populations, routes, or long-term use^{[6 ]}.

Compounding-specific concerns

FDA Category 3 status reflects inadequate support for the compounding nomination, not an approval or comprehensive safety review^{[2 ]}. Grey-market ARA-290 products add additional risks: uncertain identity, purity, sterility, peptide aggregation, endotoxin contamination, inaccurate concentration, and route-specific formulation issues.

Because ARA-290 is derived from erythropoietin biology, reviewers should also avoid overcorrecting in the other direction. The peptide was designed to avoid erythropoiesis, and early papers frame that as a distinguishing feature^{[6 ,11 ]}. The appropriate safety language is therefore not that it behaves like erythropoietin, but that nonerythropoietic design does not remove the need for human safety data.

Long-term safety

Long-term safety remains limited. Patients with sarcoidosis, neuropathy, diabetes, autoimmune disease, kidney disease, or chronic pain are medically complex and may be using immunosuppressants, analgesics, glucose-lowering drugs, or other therapies. No unsupervised use should be inferred from early clinical trials.

Available through

ARA-290 is not currently available through FDA-compliant channels in the United States as of 2026-05-07^{[1 –3 ]}. ProPeptideGuide does not link to or endorse grey-market vendors.

No provider-platform listings should be added unless an FDA-approved product, active clinical trial, expanded-access program, or other lawful pathway is verified.