Intranasal neuroEPO slows Alzheimer’s progression

An intranasally administered recombinant human erythropoietin without erythropoietic activity and shorter plasma half-life (neuroEPO) restores cognitive function or delays progression in most patients with mild-to-moderate Alzheimer’s disease, results of the phase II/III double-blind, placebo-controlled ATHENEA trial have shown.

NeuroEPO is a neuroprotective agent that activates multiple signalling pathways, which inhibit apoptosis, reduce cellular neuronal death, inflammation, and local oedema. According to in vivo and vitro studies, neuroEPO stimulates neurogenesis and neuroplasticity that controls homeostasis and rescues brain functions damaged by brain injury. [Neurosci Lett 2002;321:73-76; Pharmaceuticals 2020;13:424] Its safety was demonstrated in healthy volunteers, patients with spinocerebellar ataxia type 2 and patients with Parkinson’s disease. [BMC Neurol 2017;17:1-9; Mov Disord 2022;37:1516-1525; MEDICC Rev 2021;23:49-54]

ATHENEA was a 48-week, phase II/III, randomized, double-blind, parallel, multicentre, adaptive, placebo-controlled trial, which enrolled 174 participants (mean age, 74.0 years; female, 71.2 percent) with mild-to-moderate Alzheimer’s clinical syndrome in Havana, Cuba from September 2017 to September 2020. Participants were randomized in a 1:1:1 ratio to receive 0.5 mg or 1.0 mg of neuroEPO or placebo intranasally 3 times per week for 48 weeks. A total of 148 patients completed the trial: 50 in the neuroEPO 0.5 mg group, 49 in the neuroEPO 1.0 mg group and 49 in the placebo group. [Alzheimers Res Ther 2023;15:215]

The primary outcome of adjusted median change in Alzheimer’s Disease Assessment Scale (ADAS-Cog11) score from baseline at 48 weeks was -3.0 in the neuroEPO 0.5 mg group, -4.0 in the neuroEPO 1.0 mg group and 4.0 in the placebo group. NeuroEPO showed good results in both mild and moderate Alzheimer’s disease (AD). However, the researchers noted that the effect of neuroEPO treatment was greater in patients with mild disease, suggesting that earlier use of the agent could be more beneficial.

A clinically significant reduction of ≥4 points in ADAS-Cog11 score was reported in 49.1 percent and 58.9 percent of patients treated with neuroEPO 0.5 mg and 1.0 mg, respectively, suggesting some level of cognitive function restoration, according to the researchers. At the same time, an ADAS-Cog11 score increase of ≥2 points was reported in 86 percent of placebo recipients.

ADAS-Cog11 scores stabilized or improved in 86.0 percent and 82.1 percent of patients in the neuroEPO 0.5 mg and 1.0 mg groups, respectively, vs 14.0 percent of patients in the placebo group. Furthermore, 92.9 percent of neuroEPO recipients had no change in Global Deterioration score at 48 weeks vs 69.4 percent of participants receiving placebo. “These are important findings, because disease control and progression delay are the primary objectives of current AD drug development pipeline,” commented the researchers.

Adverse events (AEs) occurred in 8.8 percent, 5.4 percent and 5.3 percent of patients in the neuroEPO 0.5 mg, 1.0 mg and placebo groups, respectively. “NeuroEPO has a very good safety profile, especially compared with other drugs approved for the treatment of AD, where a greater number of AEs, many of them serious, have been reported,” noted the researchers.