NeuroEPO advances in favor of memory

One of the most promising products that the Center for Molecular Immunology (CIM) has today is NeuroEPO, a neuroprotective drug that was obtained last March by the Cuban regulatory agency, the Center for State Control of Medicines, Equipment and Medical Devices (Cecmed) a conditional health registration for the indication of mild and moderate Alzheimer’s disease.

The results of this molecule—hope for many people in Cuba and the world—and the update on its clinical development were presented at the Neuroscience Symposium of the BioHabana 2022 congress.

The good news is that at the beginning of May there will be a workshop coordinated with the Public Health authorities, with the aim of unifying criteria, training researchers and doctors who work with dementia in the capital, and standardizing the country’s clinical sites that will participate. in the next two trials with this drug.

“It is a product that has generated a lot of expectations, since it is aimed at a very complex orphan disease, such as Alzheimer’s; which constitutes a major health problem worldwide and in our country. This molecule has given good results in the clinic, where most of the medications that exist today control the symptoms, but do not prevent the progression of the disease, which makes NeuroEPO very attractive,” Dr. Kalet told Cubadebate. León Monzón, deputy director of CIM and deputy general director of research and development of the scientific institution.

For the treatment of Alzheimer’s there are some drugs in the world used to palliate the symptoms and, in fact, if they slow down the evolution of the disease it is for a very short time, he pointed out.

“The results we are seeing with NeuroEPO are very positive. We are seeing patients who are stabilized after a year of treatment: the vast majority, almost 80% of the subjects studied. Even within the patients who stabilize, there is a part that is better at the end of the therapy than at the beginning of the treatment, which is a much higher result than what has been seen in the scientific literature”, León Monzón specified.

Several companies present at BioHabana 2022 have shown interest in NeuroEPO, he said. “We are strongly looking for some international collaboration to also start a phase III clinical trial abroad that confirms the Cuban data, and that could be what would allow us access to the market outside the country,” he commented.

Two clinical trials in Cuba that are expected to begin in the second half of 2022, one phase III and one phase IV, are the next steps in the clinical development of this molecule, informed Doctor of Science Leslie Pérez Ruiz, clinical promoter of NeuroEPO in Alzheimer’s and other neurodegenerative diseases, from the CIM.

According to the researcher, the phase III clinical trial will take place in Havana due to the technology and logistics required for its design, while the phase IV trial will take place in the rest of the country.

“At this time, the Clinical Trials Coordination Center (Cencec) is evaluating the clinical sites both in Havana and in the other provinces to see the availability, structure and human resources that will be participating. Neuropsychologists, for example, are essential for research, because they are the ones who develop most of the neuropsychological batteries that are administered to patients”, explained the expert. He added that a database is already being created to evaluate the patients, so that when the two clinical trials begin, the inclusion is not delayed and the research advances as quickly as possible.

What characteristics will the next tests have?

As detailed by Dr. Giosmany Bringas Sánchez, a specialist at the Institute of Neurology and Neurosurgery (INN) and principal investigator of the phase III clinical trial, this study will take place in the capital and it is estimated that it will have a sample of 500 patients. The INN will be the lead center for the phase III trial, and the subjects will be distributed to different hospitals in the city for follow-up and treatment.

“The most significant thing about this phase in relation to phase II/III is that molecular biomarkers will be used that will more accurately support the scientific results and will provide a confirmatory diagnosis of the disease, which during the previous phases of research were not available or in the world or in Cuba,” he said.

These are cerebrospinal fluid markers, tomography and blood tests, he exemplified.

In this sense, Pérez Ruiz explained that in the previous study phases, the clinical criteria were followed to diagnose the disease and it was shown that the patients had cortical and hippocampal atrophy in the nuclear magnetic resonance, in addition to the fact that the simple photon emission tomography showed that there was hypoperfusion in the parieto-temporal region, which is characteristic of Alzheimer’s disease.

Specific markers will now be used, such as amyloid beta protein, whose abnormal deposits in the brain are associated with Alzheimer’s.

“The other novel element in this trial is that it will be done against an active control: NeuroEPO against Donepezil, one of the products that has been approved by the FDA since the 1990s to treat Alzheimer’s disease. The clinical trial will have three arms: only NeuroEPO, an active comparator of these products and finally the combination of both; important information because in Cuba there is no treatment as such for this type of dementia”, said the CIM specialist.

He considered that if it is shown that there is a synergy between both products—with different mechanisms and actions—it is possible that we can penetrate other markets that do have the treatment available and perhaps by adding NeuroEPO they will obtain better results.

According to Pérez Ruiz, since the patients are diagnosed not only clinically but also molecularly, those who are not confirmed to have Alzheimer’s disease, but who have another type of dementia, will also be analyzed.

“This is an essential piece of information because NeuroEPO may not only treat Alzheimer-type dementia, but also treat other dementias. The clinical trials that have already concluded have shown that cerebral perfusion increased in the treated subjects, so it is therefore possible that this molecule has some influence on vascular or mixed dementia”, specified the specialist.

The phase IV clinical trial is the one that will be carried out in the rest of the country’s provinces except Havana, the Master of Science Saily Sosa Pérez, principal investigator of the phase II/III and IV clinical trials, told Cubadebate.

“This study is more directly related to normal medical practice. It will include a sample of 1,500 patients, which will allow it to reach a greater number of people in Cuba. At this stage, the clinical sites in each province are being selected,” said the also researcher of the Provincial Service of Comprehensive Community Care for Memory Disorders of the Iván Portuondo general teaching hospital, in the province of Artemisa.

This service was the main site of the phase II/III clinical trial and will again be the main site of phase IV, he added.

It is a reality that we do not have affordable medicines in the country for patients with Alzheimer’s and NeuroEPO has proven to be safe, effective, accessible because it is Cuban and with minimal adverse events, none related to the product. It is for nasal application, which represents an advantage because it does not pass into the systemic circulation and adverse events are fewer. Hence, this molecule could become a potential medicine for the treatment of Alzheimer’s patients not only in Cuba but in the world. With this we would gain independence and technological sovereignty because it is a 100% our product”, commented Dr. Sosa Pérez.

Certainly —he insisted— the product does not cure the disease, “but as far as the cure for Alzheimer’s arrives, with NeuroEPO we can dignify the path of these patients who still do not have a total solution with the slowing of cognitive deterioration, or with a slight improvement. How much would we not improve the quality of life of these patients or the situation of the caregivers?

It happens, added the expert, that Alzheimer’s disease has a high economic and social cost, but the most important cost is the human one. “This dementia is the first cause of disability in older adults, the first burden of dependency, of overload of caregivers, the sixth cause of death in our country. For every patient with Alzheimer’s, at least two caregivers become ill from a physical and psychological point of view, so NeuroEPO would allow us to treat this binomial: the patient and the caregiver, who also requires care,” he said.

“What is proven is that clinical trials are the only hope to open the door to a definitive cure for the disease. We must try to demand a greater commitment from everyone to science, which is what will definitively allow that door to be opened”, said the researcher.