Since the beginning of the Covid-19 pandemic, the dream, and the absolute need, it has been to have treatments that avoid the serious consequences - the majority translated into thousands of deaths - which originated the infection and, if possible, even get His prevention. Science and medical clinic used from the first months of 2020 drug-based strategies with different mechanism of action and with diverse evidence, depending on their degree of effectiveness: from interleukin antagonists, such as anakinra, going through hydroxychloroquine and chloroquine; antiretrovirals such as favipiravir, ritonavir, lopanavir and molnupirabir; Ace-2 recombinants, interferons, ivermectin, oleandrine, cytokine inhibitors such as Sarilumab and Tocilizumab, until reaching cellular therapies. Each of them, the evidence has been diverse, depending on their degree of usefulness. Thus, some have made practically contemplated, others continue to be the subject of more complete clinical studies and, the least, such as antiviral remades, have become the current standard therapy together with the dexamethasone for patients with higher severity. More than one year and a half of the viral explosion, the more than 1,600 clinical trials underway with potential molecules - whose development runs in parallel with those of vaccines - begin to offer certain results that, in the coming months, could be a reality and convert to Many of the drugs tested -fundately antiviral, anti-inflammatory drugs and monoclonal antibodies - in the new future shields against SARS-COV-2.A a thousand of these studies evaluate repositioned drugs and 250 new, according to the latest data from PhRMA, US employer of the pharmaceutical industry. Starting into account that people continue to be ill and downtown and that immunity that induces the current vaccination seems Decreasing over time, in addition to providing reinforcement doses, it is absolutely necessary to have therapies that, first, reduce the viral load and that, in addition, control the inflammatory hyperresses, modulating the immune.
According to the specialists, the most recent knowledge indicates that the current drugs that are tested against the COVID-19 are, therefore, to two ways: antiviral action, scope in which there is already remades-First and only approved for this purpose and that can be administered jointly with dexamethasone as standard therapy - and in which a new section is opened with the study of aplidine, among others under development. The other mechanism of action analyzed and necessary is the effect of anti-inflammatories. A third therapeutic paw would focus on monoclonal antibodies (AM), with a passive immunity that could be useful in some subgroups of patients. In these moments, explains Guillermo Master, of the Internal Medicine Service of the Hospital 12, Madrid, There is such a wide range of essays that it is possible that there are more questions than answers about what therapies are more convenient, although it is a fact that in the coming months will have different options that must be consolidated by the scientific community and by regulatory agencies of drugs
"The road is directed to avoid viral pneumonia. Therefore, the objective would be to achieve an oral antiviral that could be administered to the diagnosis of the infection from the health centers. For the patients who reached the hospital it would be necessary to administer a more powerful antiviral. , orally or intravenously, adding control of the inflammatory response, "says Master." Of course, patient profiles will have to be analyzed, if they are inflammatory, or situations of the disease to offer more concrete responses. If the infection is It makes endemic, it is necessary to continue investigating useful therapies, "emphasizes the internist.
The theoretical approach to developing this typological variety of molecules should not entail, in principle, greater problems. But the reality is that therapies are "are making rogar", although Vicente Estrada, head of the Infectious Unit of the Clinical Hospital of Madrid, Matiza: "Great efforts have been made to develop and approve new molecules during the pandemic. Really In recent months, the approach of the Covid-19 has varied a lot, fortunately. We know that remdoreivir and dexamethasone are the standard, but it is very likely that in the coming months we see new findings in terms of drugs, both in antiviral and anti-inflammatory version. ".
Precisely, the Estrada team has participated in an international clinical trial with the Baricitinib anti-inflammatory anti-inflammatory, indicated for rheumatoid arthritis, whose data has just published The Lancet Respiratory Medicine.
In this study, the COV Barrier, in which six Spanish centers have participated, has been observed that this molecule is superior to placebo in terms of reducing the risk of global mortality by 38% at 28 days. Thus, the US FDA has expanded the authorization of emergency use for Baricitinib, allowing administration with or without remadesivir.
Another molecule, the so-called PTC299, cousin sister of the leflunomide, is part of a multicenter international trial. "With antiviral effect, but also with some anti-inflammatory activity, it could serve as an adjuvant to the established treatments with remdden and dexamethasone and with the peculiarity that it can be administered orally, as long as the patient does not require some form of mechanical ventilation, already that can not be administered parenterally, "explains Guillermo Maestro, whose hospital, on October 12, has included 25 patients. Although there is still no preliminary data, the objective of this molecule would be" avoiding severe respiratory failure, By limiting the progression of the roads that lead to the 'Cytokine storm, when administering it early, in the first seven days with symptoms, in conjunction with the standard drugs, to stop the progression of the well-known Citocin Storm. "
But, really, at what point are the investigative career in terms of the development of new drugs against the Covid-19?
In the field of antivirals, remadesivir, standard therapeutics whose first initial data were discussed, just confirmed - in an international study of the Foundation against AIDS and infectious diseases, Irsicaixa and the Service of Infectious Diseases of the Germans Hospital Trias I PUJOL- that its Endovenose Administration during the three days after the diagnosis of Covid-19 reduces the risk of hospitalization by 87% in people susceptible to suffering from the disease in a stern way, according to Roger Paredes, Chief of Infectious Hospital. Other Antiviral In evaluation, they are favipiravir and meimepiB, after observing the scarce effectiveness of initial combinations with lopinavir and ritonavir.In the spot is also a Spanish compound, aplyline (plitidepsin) which, according to the pharmacist who develops it, achieves an 80 % of hospitable highs in 15 days or less. He has entered Phase III and, according to Vicente Estrada, who has participated in developmental trials, "seems to have good potential."
The drug, used so far against oncological processes, showed at the beginning of the pandemic that its mechanism of action also made it an antiviral. Now, after preclinical trials and the first clinicians, the data show its potential as treatment against coronavirus.numerous are also anti-inflammatory or immunomodulators that are tested as a form of treatment or prevention of various organ dysfunction and pulmonary injury that It causes inflammation associated with SARS-COV-2 infection. This would be the case of the aforementioned baricitinib, used for rheumatoid arthritis, with anti-inflammatory characteristics and antiviral activity and which, according to the US FDA, can be used in combination with remDesivir for hospitalized patients who require supplementary oxygen supply.
After the start-up of the Solidarity study of the World Health Organization (WHO), which in its first phase did not achieve totally satisfactory results after testing in patients four treatments -hydroxicloroquine, remdden, interferon and lopinavir and ritonavir-, this organism He has given green light to a second stage of the study with the start-up of Solidarity Plus. It will be carried out in patients hospitalized with three new possible treatments: the antimalarial artisunate; Imatinib, indicated for some types of cancer; E Infliximab, a monoclonal antibody for rheumatoid arthritis and other diseases of the immune system.
In the new study, in which researchers will participate in 600 hospitals from 52 countries - in Spain has not yet begun - the three molecules have been donated by their manufacturers -ipca, Novartis and Johnson & Johnson, respectively - and selected by a panel Independent experts "Given its potential when reducing the risk of death in COVID-19 patients," said Tedros Adhanom Ghebreesus, General Director of WHO, in the presentation of the new essay.
Monoclonal antibodies (AM) are proteins created in laboratory that can help the immune system combat viruses. There are several medications with AM available that have been tested in SARS-COV-2 disease: combinations of Bamlanivimab and Etesevimab, as well as Casirivimab and Imdevimab, and Sotrovimab.Por now, the US regulatory agency FDA has given the approval good to Three monoclonal antibodies and the European Medicines Agency (EMA) initiated the evaluation of Bamlanivimab and Etevimimab monoclonal antibodies and the combination of Casirivimab / IMDEVIMAB.The drugs are used to treat Mild to moderate COVID-19 in people who They run an increased risk of serious diseases due to Covid-19. In order for their effectiveness to be greater, they must be administered after the emergence of the symptoms of disease and before hospitalization. Recently, the European Commission has chosen some molecules against the COVID-19 for the centralized purchase of products that will begin next month. October. Four of these therapies are, precisely, monoclonal antibodies, although an immunosuppressor, approved for this indication, but could be extended for the treatment of viral infection.
Science does not forget the approaches based on cell therapy. The most innovative alluded to the use of stem cells, such as that carried out by the Group of Damián García-Olmo, in the Jiménez Díaz Foundation, of Madrid, for moderate to severe disease.More recently, Treatments based on memory T lymphocytes, as the recently published in the EclinicalMedicine, the group of The Lancet, coordinated by the Spaniards Antonio Pérez Martínez, the La Paz Hospital; Cristina Ferreras, from the IdiPaz Research Institute (both in Madrid), and Bernat Soria, from the Miguel Hernández University of Elche, in Alicante. In this first world study it has been observed that "memory t lymphotics offer 'signs' efficiency in patients with moderate to severe", indicated this newspaper Soria. The FDA also authorized emergency therapy with hyperinmune plasma ; This is blood from people recovered from the Covid-19. Although its usefulness is still being evaluated, this strategy - entered into hospitalized phase of the disease or with a weakened immune system - is also tested as a potential preventive therapy, similar to the action that could achieve anti-COVID vaccination.
The Spanish pharmaceutical Grifols, for example, began phase III essays, which are waiting for more concrete results.
Some of the molecules in clinical trials will be part of the therapeutic package that, according to the European Commission announced, may be available between 2021 and throughout 2022. In fact, it is intended to prepare a portfolio of at least 10 possible therapies for the Coronavirus before October, which, in addition, will take into account the contributions made by the group of experts in relation to the variants of the virus.
However, one of the most interesting aspects focuses on that, according to patient profiles or disease patterns, molecules with different mechanism of action could be combined.
"There goes the shots," considers Estrada, in line with what is observed by experts from the Spanish Society of Infectious Diseases and Microbiology and the Spanish Research Network in Infectious Pathology, which have published in Infectious Magazine Designs a study in the that three phenotypes of patients who correlate themselves were identified with mortality. According to Estrada, "what has been observed is that in the precocious and acute phase of the disease, in the first three or four days, it should be chosen by antivirals, ideally That they were the most powerful and without side effects. For the inflammatory stage, in addition to the current dexamethasone, baricitinib could appear, for example, without forgetting the potential of aplidine and other studied that could offer benefits. "
After the presentation, at the Idweek International Conference, the data of an international study, with a major Spanish participation, which indicates that dealing with remadesivir immediately after the diagnosis of Covid-19 reduces the risk of hospitalization and death in adult patients vulnerable by Serious illness by 87%, the turn of evaluating and, subsequently, begins, its effectiveness in children.This is the main objective of another global trial with remadesivir, the only antiviral approved for the treatment of SARS-VOC infection -2, in 54 children between 0 months to 18 years, Spain being one of the main recruiters, with 10 patients.
The recruitment is over and the preliminary data will be announced from the next months of October and November to be able to provide, predictably, the drug at the clinic at the beginning of next year.
Pablo Rojo, from the Hospital Pediatrics Service October 12, from Madrid, and coordinator of this essay in Spain, explains that, in addition to checking the pharmacokinetics and the safety of the antiviral, it is expected that its benefits are similar to those of adults .
"However, being the only antiviral that, so far, has demonstrated some effectiveness, it could be useful for children with a moderate to severe disease. The challenge would be to reduce the days of symptomatology, which could avoid the passage of many of They to the UVI, for example. "
The pattern of the study with remadesivir in children is based, as in the adult, in its intravenous administration "at the beginning of the symptoms - followed by five days of treatment - in patients with moderate involvement; pneumonia with oxygen support needs , for example ". InDDesivir, other adult drugs that could be transferred to children are considered. In fact, the October 12 team will also begin another essay with the anti-inflammatory baricitinib in a pediatric population.
"Even though children have a less serious illness, there is a small group in which it may not be so benign. It is always advantageous to have more tools; from after the most promising by regulatory agencies. Thus, it is Wait for the effectiveness demonstration in adults to start trials in children, "redes.
It does not arise, in principle, its use in multisystemic inflammatory syndrome (SIM) because it is a late sequel to infection in children's population.
Date Of Update: 15 October 2021, 16:52
