Cibinetide is a synthetic peptide, also known as ARA 290 or helix B surface peptide. It is derived from a specific part of erythropoietin (EPO), a naturally occurring protein. Unlike EPO, cibinetide is designed to avoid stimulating red blood cell production, a common side effect of EPO treatments. This design focuses its effects on tissue protection and repair mechanisms.
How Cibinetide Works
Cibinetide operates by acting as a selective agonist of the innate repair receptor (IRR). This receptor is a heterodimeric complex composed of the erythropoietin receptor (EPOR) and CD131, also known as the β common cytokine receptor. The IRR becomes more active in situations involving tissue injury, lack of oxygen (hypoxia), or metabolic stress.
Upon activation, cibinetide triggers signaling pathways that promote anti-inflammatory responses and tissue repair. This includes neuroprotection and improvements in vascular health.
Cibinetide’s therapeutic effects stem from its ability to reduce inflammation and promote nerve regeneration. It antagonizes the transient receptor potential vanilloid-1 (TRPV1) ion channel, which is involved in pain sensation and neurogenic inflammation in small nerve fibers. This interaction may contribute to its ability to relieve mechanical hypersensitivity. The compound’s mechanism also involves anti-apoptotic (preventing cell death) and anti-permeability effects, important for tissue integrity and function.
Conditions Cibinetide May Treat
Cibinetide is under investigation for various medical conditions, primarily those involving inflammation and tissue damage. It shows promise in addressing neuropathic pain, particularly in patients with sarcoidosis and diabetic neuropathy. In these conditions, cibinetide reduces inflammation and promotes the repair of damaged nerves, which can alleviate symptoms like pain and tingling.
For diabetic neuropathy, studies indicate cibinetide may improve symptoms in individuals with type 2 diabetes, potentially leading to a better quality of life. The peptide’s anti-inflammatory properties are also broadly beneficial, helping reduce systemic inflammation in various inflammatory and autoimmune conditions and potentially slowing disease progression.
Cibinetide also holds potential for tissue protection and repair, especially in cases of injury, hypoxia, or restricted blood flow (ischemia). This includes benefits for wound healing and vascular health. In models of diabetic retinopathy, cibinetide has been shown to inhibit vascular leakage and swelling, while also protecting against degeneration of retinal blood vessels and neuroglial cells. It has also demonstrated potential for improving metabolic control in both preclinical and clinical studies.
Cibinetide’s Journey Through Clinical Trials
Cibinetide has advanced through various stages of clinical trials, primarily focusing on its efficacy in treating neuropathic conditions. It has completed Phase 2 trials for neuropathy associated with sarcoidosis. In a Phase 2b study involving 64 sarcoidosis patients with painful neuropathy, cibinetide was administered daily for 28 days. The trial assessed nerve fiber loss and repair, showing significant nerve regrowth, pain reduction, and improved functional capacity, particularly at a 4 mg dose.
Beyond sarcoidosis, cibinetide has also shown positive results for nerve regeneration and symptomatic improvements in diabetic peripheral neuropathy. An exploratory Phase 2 open-label clinical trial also evaluated cibinetide for the treatment of diabetic macular edema (DME). In this 12-week study, cibinetide was found to be safe. Some participants showed improvements in central retinal thickness, tear production, diabetic control, and albuminuria, though overall visual acuity did not significantly improve.
The development of cibinetide is ongoing, with Araim Pharmaceuticals leading the efforts. Positive outcomes from completed Phase 2 trials have laid the groundwork for further clinical development. Cibinetide has also received orphan drug designation from the FDA for the treatment of neuropathic pain in patients with sarcoidosis and for the prevention of graft loss in pancreatic islet transplantation. This designation aims to encourage the development of treatments for rare diseases.