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Peptide Spencer

Non-hematopoietic erythropoietin-derived peptide; innate repair receptor (EPO receptor/CD131) agonist; investigational

ARA-290 (cibinetide)

Also known as ARA 290, ARA290, cibinetide, helix B surface peptide (HBSP), pyroglutamate helix B surface peptide (pHBSP)

Controlled human trials

Not FDA-approved. On FDA's 503A list (May 14, 2026): Category 3, nominated without adequate support. Source, May 14, 2026

Identity. ARA-290, cibinetide, and HBSP/pHBSP are names for the same 11-amino-acid peptide derived from erythropoietin (PMID 32674280). It is not erythropoietin or the full EPO molecule. Preclinical papers sometimes call it pHBSP. No ambiguity with other products sold under the name ARA-290 was found.

At a glance

These dosages are a helpful guide, not a prescription. Every clinician is expected to do their own due diligence before prescribing.

  1. Start

    4 mg subcutaneous daily12

    Human study
Frequency
daily12
Route
subcutaneous (self-administered)2
Course
28 days12

Trial doses are route-specific: 2 mg IV three times weekly does not convert to 4 mg SC daily, and 8 mg/day showed no added benefit.

Calculate this dose

Dosing detail

Human studies

Human study

  • Sarcoidosis with symptoms of small fiber neuropathy; ARA 290 vs placebo

    2 mg3

    Route
    intravenous
    Frequency
    three times weekly
    Duration
    4 weeks
    n
    22 (ARA 290 n = 12; placebo n = 10)
    Design
    Randomized, double-blind, placebo-controlled exploratory pilot
    Source quote
    A total of 22 patients diagnosed with sarcoidosis and symptoms of SFN were enrolled in a double-blind, placebo-controlled exploratory trial consisting of three times weekly intravenous dosing of ARA 290 (2 mg; n = 12) or placebo (n = 10) for 4 wks.

    Finding. Significant SFNSL improvement vs placebo at week 4; BPI and FAS improved equivalently in both groups; no safety concerns.

    Note. Intravenous research regimen. Doses are route-specific and not interchangeable with the subcutaneous regimens below. 2 mg IV three times weekly is 6 mg/week. 4 mg SC daily is 28 mg/week. Never carry the 2 mg figure across to subcutaneous use.

  • Sarcoidosis-associated small nerve fiber loss and damage; ARA 290 vs placebo

    4 mg1

    Route
    subcutaneous
    Frequency
    daily
    Duration
    28 days
    n
    38 (ARA 290 n = 21; placebo n = 17)
    Design
    Investigator-initiated, single-site, double-blind, placebo-controlled trial
    Source quote
    Based on these data, the 4-mg SC group was selected for the daily dosing regimen of this trial.

    Finding. Improved neuropathic symptoms, increased corneal small nerve fiber density and 6-minute walk distance vs placebo.

    Note. The investigators chose the 4 mg SC group for daily dosing based on earlier data, and the paper does not say which data. 4 mg SC daily is 28 mg/week, while 2 mg IV three times weekly is 6 mg/week, so the two regimens are not interchangeable.

  • Type 2 diabetes with painful neuropathy; ARA 290 vs placebo

    4 mg2

    Route
    subcutaneous (self-administered)
    Frequency
    daily
    Duration
    28 days, then followed an additional month without treatment
    n
    48 analysed (49 enrolled)
    Design
    Phase 2, double-blind, placebo-controlled, investigator-initiated
    Source quote
    ARA 290 (4 mg) or placebo were self-administered subcutaneously daily for 28 d and the subjects followed for an additional month without further treatment.

    Finding. Improved HbA1c and lipid profiles and PainDetect scores; corneal nerve fiber density rose in subjects with CNFD >1 SD from normal.

  • Sarcoidosis-associated small nerve fiber loss and neuropathic pain; dose-ranging vs placebo

    1, 4, or 8 mg/day4

    Route
    subcutaneous (first dose at the research site, then self-administered daily for an additional 27 days)
    Frequency
    daily (mg/day as stated)
    Duration
    28 days
    n
    64 randomized (assignment of two 8 mg subjects is not established; analysed set smaller)
    Design
    Phase 2b randomized trial
    Source quote
    The placebo-corrected mean change from baseline CNFA (μm2) at day 28 was 109 (95% confidence interval [CI], -429, 647), 697 (159, 1236; P = 0.012), and 431 (-130, 992) in the 1, 4, and 8 mg groups, respectively.

    Finding. Three separate arms, not a range. Only the 4 mg/day arm was significant for the primary endpoint, the placebo-corrected change in CNFA at day 28 (units as reported in the paper). The 8 mg arm did not outperform 4 mg, so there is no evidence that escalation above 4 mg adds benefit. Pain improved in all groups.

  • Diabetic macular edema, treatment-naive, central retinal thickness >400 micrometres

    4 mg5

    Route
    subcutaneous (self-administered)
    Frequency
    daily
    Duration
    12 weeks (84 days)
    n
    9 enrolled; 8 completed
    Design
    Open-label, single-arm, investigator-led pilot phase 2
    Source quote
    Participants were instructed to self-administer cibinetide subcutaneously at a dose of 4 mg/daily. [...] Treatment continued for 84 days unless discontinued earlier due to withdrawal or >10 letter loss.

    Finding. No mean improvement in BCVA, CRT, sensitivity or tear production; NEI VFQ-25 composite +2.7; no SAEs, no anti-cibinetide antibodies.

  • Healthy volunteers; neuropsychological model of antidepressant action (not a therapeutic dosing study)

    2 mg6

    Route
    not reported in the abstract
    Frequency
    not reported in the abstract; outcomes assessed one week after administration
    Duration
    not reported in the abstract
    n
    36
    Design
    Double-blind, randomized, parallel-group vs placebo
    Source quote
    Healthy participants (N=36) received ARA290 (2mg) or placebo in a double-blind, randomized, parallel-group design. Neural and cognitive effects were assessed one week after administration.

    Finding. Modulated some emotional-processing measures; no effects on mood; did not support an antidepressant-like profile.

Clinical practice

Clinical practice

No peer-reviewed review, compounding-pharmacy protocol, clinic prescriber protocol, or textbook reports clinician practice dosing. Online sources only restate the trial regimens, so no practice numbers are given. The only well-sourced regimen is the trial regimen: 4 mg subcutaneous daily for 28 days in the neuropathy trials, and 12 weeks in one DME pilot. Titration steps, a ceiling, and cycle repetition have no citable source.

Safety

Serious warnings

  • Investigational peptide with no approved product located, so no label warnings were reviewed. A claim that no FDA label exists could not be confirmed from the cited FDA page, so check Drugs@FDA and DailyMed.7
  • Suicidal ideation case report: the DME trial authors state 'one individual with a pre-existing history of depression out of over 200 treated had suicidal ideation while using cibinetide'. They screened with the C-SSRS, and no DME participant exhibited suicidal ideation.5
  • Type 2 diabetes trial (Brines 2015): four serious adverse events occurred in the ARA 290 arm. Two were judged unlikely related and two possibly related; the paper does not say which is which. One subject on daily furosemide had worsening renal insufficiency (creatinine 119 to 159 umol/L), and the safety committee stopped ARA 290. A 70-year-old man with severe cellulitis had a fatal myocardial infarction about 2 weeks after his last dose, judged unrelated by the safety committee.2
  • Dose-ranging trial (Culver 2017): serious adverse events occurred in 2 subjects in the 1 mg group (considered unrelated). One subject in the 8 mg group had suicidal ideation, considered possibly related. Source: the IOVS full text, not independently rechecked.4

Contraindications

  • None established, as there is no label. The DME trial excluded pregnancy or breastfeeding, concurrent erythropoiesis-stimulating agents, systemic or topical steroids, and investigational medications. These were trial exclusions, not label contraindications.5
  • The sarcoidosis dose-ranging trial's exclusion criteria are not yet confirmed from a cited source. They are reported to include erythropoiesis-stimulating agents, serious malignancy within 5 years, and abnormal ECG. No data exist in patients with active or recent malignancy, and no tumour-promotion risk has been sourced.8

Adverse effects

  • DME pilot (n = 9): increased triglycerides 5/9, headache 4/9, head cold 4/9, increased glucose 3/9, nausea 2/9. Headache, head cold, and nausea were felt to be potentially related. Subcutaneous administration was well tolerated, with no SAEs.5
  • Sarcoidosis daily SC trial: no serious adverse events through dosing and 12 weeks of follow-up. One ARA 290 patient had a moderate adverse event of long-term 14 kg weight loss, which per the full text of the cited paper began before study entry and persisted after dosing. No anti-ARA 290 antibodies were detected.1
  • Sarcoidosis IV pilot (2 mg three times weekly): 'No safety concerns were raised by clinical or laboratory assessments.'3

Monitoring

  • The DME pilot monitored anti-cibinetide antibodies (none developed), HbA1c, triglycerides, glucose, and suicidal ideation by C-SSRS. These were trial procedures, not a clinical recommendation.5
  • Trial signals a prescriber may watch. These are trial observations, not guidelines, and no regulator or guideline monitoring schedule exists. Renal function, especially with diuretics (renal SAE in the type 2 diabetes trial). Fasting glucose, HbA1c, and triglycerides (increases in the DME pilot; the authors noted that non-fasting status may explain them). Body weight. Depression history and C-SSRS-type screening.2

Interactions

  • No interaction studies were found. Trials excluded erythropoiesis-stimulating agents, systemic or topical steroids, and investigational drugs (DME). The effect of these combinations is unknown.5

Evidence

Small randomized, placebo-controlled phase 2 trials in sarcoidosis small-fiber neuropathy and type 2 diabetes neuropathy report improved neuropathic symptoms and corneal nerve fiber measures. Most are sponsor-affiliated and 28 days long. A 9-patient open-label diabetic macular edema pilot showed no mean visual benefit. The evidence applies only to neuropathic symptoms and corneal nerve fiber endpoints in patients with sarcoidosis or type 2 diabetes. No controlled human data exist for any other use. Endpoints are partly surrogate (corneal nerve fiber area) or patient-reported. No phase 3 trial or regulatory approval was found. Dosing evidence comes from trials only, and no clinician practice protocol was located.

Mechanism

Synthetic 11-amino-acid peptide derived from the B helix of erythropoietin. It acts at the innate repair receptor (EPO receptor/CD131 heteromer). This drives anti-inflammatory and anti-apoptotic tissue protection without erythropoiesis. The diabetic macular edema (DME) trial paper states that receptor signalling requires systemic concentrations of at least 1 nM.5

Availability

Amounts offered

  • 5 mg
  • 10 mg

Custom strengths on request.

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References

According to PubMed

  1. 1ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density.Mol Med 2013;19(1):334-45 (Dahan et al.), 2013
  2. 2ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes.Mol Med 2015;20(1):658-66 (Brines et al.), 2015
  3. 3Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy: a randomized, double-blind pilot study.Mol Med 2012;18(1):1430-6 (Heij et al.), 2012
  4. 4Cibinetide Improves Corneal Nerve Fiber Abundance in Patients With Sarcoidosis-Associated Small Nerve Fiber Loss and Neuropathic Pain.Invest Ophthalmol Vis Sci 2017;58(6):BIO52-BIO60 (Culver et al.), 2017
  5. 5A Phase 2 Clinical Trial on the Use of Cibinetide for the Treatment of Diabetic Macular Edema.J Clin Med 2020;9(7) (Lois et al.), full text PMC7408632, 2020
  6. 6Testing the antidepressant properties of the peptide ARA290 in a human neuropsychological model of drug action.Eur Neuropsychopharmacol 2015;25(12):2289-99 (Cerit et al.), 2015
  7. 7Bulk Drug Substances Used in Compounding Under Section 503A of the FD&C Act (page current as of 05/14/2026)FDA, 2026
  8. 8A double blind, placebo controlled Phase 2 dose ranging study of the effects of ARA 290 on corneal nerve fiber density and neuropathic symptoms of subjects with sarcoidosis (NL-OMON38804; EudraCT 2013-003016-45)Dutch ToetsingOnline registry via onderzoekmetmensen.nl, 2013

Last reviewed 2026-10-14. 34 figures checked against their sources. How this works