Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy: a randomized, double-blind pilot study

This pilot study was the first randomized, double-blind, placebo-controlled clinical trial to evaluate ARA 290 (cibinetide) in human patients with small fiber neuropathy associated with sarcoidosis. A total of 22 patients were enrolled and received either ARA 290 or placebo subcutaneously for three consecutive weeks, with follow-up through week 4.

ARA 290 is a non-erythropoietic peptide of 11 amino acids derived from erythropoietin (EPO), designed to selectively activate the heterodimeric tissue repair receptor (composed of EPOR and βcR) without stimulating red blood cell production. This receptor is expressed on nerve, immune, and endothelial cells, and its activation promotes neuroprotection and tissue repair.

In the efficacy assessment, the ARA 290-treated group demonstrated significant improvement in the neuropathy score (Small Fiber Neuropathy Screening List) at week 4 compared to placebo. Patients reported reduction in neuropathic symptoms, including pain, paresthesias, and autonomic dysfunction. The safety profile was favorable, with no serious adverse events related to treatment.

This study was particularly relevant for demonstrating that an EPO-derived peptide can treat neuropathy without the risks associated with erythropoietin (such as thrombosis and hypertension), validating the concept that the reparative and hematopoietic functions of EPO can be pharmacologically dissociated. The results paved the way for larger phase 2 studies with ARA 290.