Background: NeuroEPO, a nasal pharmaceutical solution of recombinant human erythropoietin with low sialic acid, was in clinical development for the treatment of mildmoderate Alzheimer's disease. Method:A double-blind, randomized, placebo-controlled, multicenter, prospective, with adaptive design, phase II/III clinical trial involving 174 patients with mild-tomoderate Alzheimer's, was conducted. NeuroEPO or placebo, with different doses, was administered by nasal route 3 times a weeks for 48 weeks. The primary outcome measure was score on the 11-item cognitive subscale of the Alzheimer's disease Assessment Scale (ADAS-cog11, with scores ranging from 0 to 70 and higher scores indicating greater impairment). Secondary outcome measures included Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-plus), Global Dementia Scale (GDS), activities of daily living (ADL), hippocampal volume change over time (measured with MRI), neuropsychological scales, electroencephalography (EEG) and adverse events.Result: There were statistically significant differences between neuroEPO and placebo in median change from baseline in the primary outcome at week 48. The change in ADAS-cog11 scores final-initial (PP population) for patients in the neuroEPO 0.5 mg (n= 50, median change: -4.0), neuroEPO 1.0 mg (n=49, median change: -5.0) and placebo (n=49, median change: 4.0) groups. A difference of 8.0 points CI 95% (6.0; 10.0) neuroEPO 0.5 mg vs. placebo and 9.0 points CI 95% (6.8; 11.2) neuroEPO 1.0 mg vs. placebo at week 48, (p=0.000), was observed. Patients receiving both doses of neuroEPO also showed a significant difference in global improvement (CIBIC-Plus, p=0.000) and electroencephalography (EEG, p=0.003) compared with placebo group. About hippocampal volume change, 105 patients were analyzed. From them, 58% remained stable and 42% decline hippocampus volume. No serious adverse events related with neuroEPO were reported. Conclusion:NeuroEPO improved clinical outcomes in patients with Alzheimer's disease with good security profile. Therefore, it could be useful in the treatment of these kind of patients.

Background NeuroEPO, is a nasal pharmaceutical solution of recombinant human erythropoietin with low sialic acid. Methods Phase II/III, prospective, double‐blind, randomized, placebo‐controlled, multicenter with adaptive design clinical trial involving patients with mild‐to‐moderate Alzheimer’s. NeuroEPO or placebo, with doses 0.5 or 1.0 mg 3 times a week for 48 weeks was administered by nasal route. The primary outcome measure was a score on the 11‐item cognitive subscale of the Alzheimer’s disease Assessment Scale (ADAS‐cog11, with scores ranging from 0 to 70 and higher scores indicating greater impairment). Secondary outcome measures were: % annual change of hippocampus volume by magnetic resonance imaging (MRI) studies, neuropsychological scales and adverse events. An interim analysis was made according to the criteria as established in the protocol. Results Per‐protocol‐analysis, 69 patients finished one year of treatment. 49% of the patients showed improvement, 9% remained stable and 42% got worse, according to the ADAScog11 score. Regarding the hippocampus % annual change, 48 patients were analyzed. 58% of those patients remained stable and 42% witnessed a decline in the hippocampus volume compared with the % annual change of patients with AD (∼4.4%). No serious adverse events related with NeuroEPO were reported. Conclusions NeuroEPO improve clinical outcomes in patients with Alzheimer’s disease with good security profile. Therefore, it could be useful in the treatment of this kind of patients.