Delivery of therapeutic agents as erythropoietin (EPO) into Central Nervous System through intranasal route could benefit patients with neurological disorders. A new nasal formulation containing a non-hematopoietic recombinant EPO (NeuroEPO) has shown neuroprotective actions in preclinical models. In the current study, the safety of NeuroEPO was evaluated for the first time in humans. A phase I, randomized, parallel, open-label study was carried out in healthy volunteers. They received, intranasally, 1 mg of NeuroEPO every 8 h during 4 days (Group A) or 0.5 mg of NeuroEPO (Group B) with the same schedule. The working hypothesis was that intranasal NeuroEPO produce <10% of severe adverse reactions in the evaluated groups. Therefore, a rigorous assessment of possible adverse events was carried out, which included tolerance of the nasal mucosa and the effect on hematopoietic activity. Clinical safety evaluation was daily during treatment and laboratory tests were done before and on days 5 and 14 after starting treatment. Twenty-five volunteers, 56% women, with a mean age of 27 yrs. were included. Twelve of them received the highest NeuroEPO dose. Twenty types of adverse events occurred, with headache (20%) and increase of hepatic enzymes (20%) as the most reported ones. Nasopharyngeal itching was the most common local event but only observed in four patients (16%), all of them from the lowest dose group. About half of the events were very probably or probably caused by the studied product. Most of the events were mild (95.5%), did not require treatment (88.6%) and were completely resolved (81.8%). No severe adverse events were reported. During the study the hematopoietic variables were kept within reference values. NeuroEPO was a safe product, well tolerated at the nasal mucosa level and did not stimulate erythropoiesis in healthy volunteers. Cuban Public Registry of Clinical Trials RPCEC00000157 , June 10, 2013.

Background: Advanced non-small cell lung cancer (NSCLC) has limited curative options and poor survival. Racotumomab, an anti-idiotype monoclonal antibody vaccine targeting tumor gangliosides, has shown efficacy in clinical trials. This study evaluated its real-world effectiveness as maintenance therapy following first-line chemotherapy. Materials and Methods: A multi-center observational study was conducted on 162 patients with advanced NSCLC who received racotumomab from 2012 to 2024. Effectiveness was evaluated in the intention-to-treat (ITT) cohort. Overall survival (OS) was estimated, with subgroup analyses conducted according to clinical and demographic factors. Results: The median OS was 14.9 months (95% CI: 11.7–18.1), and the 5-year survival rate reached 20%. Patients diagnosed with stage III disease, those with better Eastern Cooperative Oncology Group (ECOG) performance status, and individuals younger than 65 years experienced significantly longer survival. Racotumomab demonstrated a favorable hazard ratio compared to historical controls (HR 0.44 vs. supportive care; HR 0.55 vs. docetaxel). Conclusions: In the era of immune checkpoint inhibitors, these real-world results indicate a promising role for racotumomab in the maintenance setting for advanced NSCLC. These findings provide a strong rationale for further investigation of racotumomab in the context of modern immunotherapy, particularly in combination trials with other immunomodulatory antibodies, along with the validation of clinical and biologic predictive biomarkers.

Background: EGFR has been suggested to contribute to COPD development and progression. Excessive ligand activation of the receptor leads to epithelial hyperproliferation and increased production of mucus, together with alterations in the primary cilia. The present study was designed to evaluate the safety and effect of depleting EGF in moderate-to-severe COPD patients, with an EGF-based vaccine. Patients and methods: A phase I trial was conducted in subjects with moderate or severe COPD. The anti-EGF vaccine schedule consisted of 4 biweekly doses followed by 4 monthly boosters. The primary endpoint was the evaluation of the safety and immunogenicity of the vaccine, together with the change in FEV1 and physical function at week 24. Results: Twenty-six patients with moderate or severe COPD were included in the trial. The vaccine was well tolerated and no serious related adverse events were reported. Ninety percent of the individuals developed a protective antibody response. The specific anti-EGF antibodies had high avidity and were able to inhibit EGFR phosphorylation. At the end of vaccination, serum EGF became undetectable. At week 24, there was a clinically significant improvement in lung function, with a mean change in trough FEV1 of 106 mL. Patients also increased their physical functioning. Conclusions: The EGF-based vaccine was immunogenic and provoked an EGF exhaustion in patients with moderate-to-severe COPD. Depleting EGF might result in a meaningful increase in FEV1, with good tolerability. The current results provide new avenues to treat chronic inflammatory lung diseases associated with EGFR aberrant signaling.