ARA-290 Reconstitution Calculator

No. ARA-290 (cibinetide; pyroglutamate helix B surface peptide/pHBSP) is investigational and unapproved by the FDA for any indication. Human efficacy and safety data exist from pilot and Phase 2 trials (RCT): a 12-week Phase 2 study in diabetic macular edema, a randomized double-blind pilot in sarcoidosis small-fiber neuropathy, and additional human studies in sarcoidosis and type 2 diabetes. In the DME trial, best corrected visual acuity (−2.9 ± 5.0 letters) and central retinal thickness (+10 ± 94.6 microns) did not improve after 12 weeks; only the patient-reported NEI VFQ-25 composite score improved, and there is currently no evidence supporting ARA-290 for treating DME. It is not commercially marketed; access is via research channels or named-patient routes only.

ARA-290 is an 11-amino-acid peptide engineered from helix B of erythropoietin (EPO). It binds the heterodimeric innate repair receptor (IRR; EPOR/CD131, β-common receptor) but not the erythropoiesis-mediating EPOR homodimer, delivering anti-inflammatory and tissue-protective signaling without stimulating red-cell production. Plasma half-life is ~2 minutes, yet brief courses trigger sustained effects via reprogramming of inflammatory signaling. Downstream (animal/mechanistic): suppressed spinal microglia activation, reduced TNF-α, IL-1β, and IL-6 with lower oxidative stress.

Subcutaneous (SC). All published human studies used SC injection: 4 mg/day for 12 weeks in the Phase 2 trial. No oral formulation or oral bioavailability evidence exists; oral use is unsupported. (community protocol) Standard practice mirrors the trials: SC injection into abdominal fat with an insulin-type syringe, 1–2 times daily. No intranasal or IV human efficacy data are available.

The only human dose clearly reported in the available literature is 4 mg/day SC, used safely for 12 weeks in the Phase 2 DME trial; other human studies used daily SC dosing, but their specific doses are not reported in the available abstracts. Rat neuropathic pain studies showed a dose-response across 3–60 μg/kg with an optimum near 30 μg/kg (animal). Related human studies in sarcoidosis and T2D corroborate daily SC use. (community protocol) Common regimens: 2–4 mg/day in 28-day cycles, often split ~1.5–2 mg twice daily; weight-scaled doses extrapolated from rodent data remain unvalidated in humans, 4 mg/day is the evidence-anchored dose.

Published human exposure is limited to 12 weeks; long-term human safety beyond this is unknown. When to expect noticeable symptom changes: onset-of-benefit data in humans are not formally reported, the 12-week DME trial showed no improvement in visual acuity or retinal thickness by week 12, with only patient-reported visual function scores improving, and the treatment windows used in the sarcoidosis and type 2 diabetes studies (durations not reported in the available abstracts) reported outcomes at course end rather than time-to-effect. Durability after short courses is notable: five doses over 10 days suppressed neuropathic allodynia for up to 20 weeks in rats, and up to 15 weeks in an earlier paradigm. (community protocol) Typical use is 4–6-week cycles followed by off periods rather than continuous administration; continuous use beyond 12 weeks is untested.

Short-term human safety is favorable: in the 12-week trial there were no serious adverse events and no anti-cibinetide antibodies. Because it is non-erythropoietic, it does not raise hematocrit and avoids the thrombosis risk that has limited therapeutic EPO. Pregnancy: no human data, avoid (community protocol). In a rat preeclampsia model, pHBSP at 10–250 μg/kg improved endothelial function and reduced proteinuria by 76% (animal), but this does not establish human pregnancy safety.

Versus EPO: ARA-290 preserves tissue-protective signaling while eliminating the erythropoietic drive and thrombotic liability that stalled clinical EPO use. Versus other regenerative peptides (BPC-157, TB-4, GHK-Cu): ARA-290 acts through the EPOR/CD131 innate repair receptor rather than their separate pathways. Its strongest human evidence is in neuropathic pain and nerve-fiber regrowth, corneal nerve density in sarcoidosis and neuropathic symptoms plus metabolic control in type 2 diabetes, a clinical track record most "healing" peptides lack.

(community protocol) Store lyophilized vials refrigerated (2–8°C); after reconstitution with bacteriostatic water, refrigerate and discard after ~30 days. Do not freeze reconstituted solution; protect from light. Travel: ARA-290 is unapproved, so international carriage carries legal risk and requires documentation of a prescribing rationale. The Phase 2 trial used patient self-administration at home, supporting practical at-home SC use.