Brazil participates in global study seeking cheap treatment for Covid in poor countries

The first drug to treat Covid-19 was approved by Anvisa (National Health Surveillance Agency) in March 2021, about a year after the start of the pandemic – a record time in terms of research, production and drug approval.

This first drug was Rendesivir, from the pharmaceutical company Gilead, a type of antiviral (which makes it difficult for the virus to replicate inside the body) for hospital use. Today, there are already six drugs against the coronavirus or its effects approved by the agency for specific patients and situations (see the list below) – and none of them should be taken without a medical indication.

The WHO (World Health Organization) also has four pre-approved drugs for the treatment of Covid.

However, drugs that have had positive results in research and have been recommended by the WHO are expensive and not widely available worldwide. The same goes for drugs approved by Anvisa — drugs such as Sotrovimab and Paxlovid are expensive and not very affordable.

With that in mind, 27 international health organizations and renowned research institutions have come together to carry out a large clinical study, ANTICOV, whose objective is to identify inexpensive and affordable treatments that can be used worldwide — including in countries and regions with limited resources. .

“It is an international research coalition, a pre-clinical and clinical research platform for low-income and middle-income countries. We started in Africa and now we also have the collaboration of Brazil”, says Sergio Sosa, director of DNDI (Drugs for Neglected). Diseases Initiative), an initiative that helped create and coordinates the ANTICOV consortium.

The study has several phases — each testing different drugs — and takes place simultaneously in 13 African countries. The new phase of the study will have the participation of Brazil through the Together Trial, a Brazilian platform that joins ANTICOV and will coordinate clinical research in the country. Up to 600 Brazilian patients must participate in the research, which will be carried out in 21 different locations —mostly in the SUS (Unified Health System)— and will have the participation of dozens of researchers and doctors.

Sosa says it is extremely important that drug research be carried out in developing countries, as this makes it easier to make drugs available to the population.

“Until recently, 90% of research was carried out in the global north (rich countries like the USA or countries in Europe). Now we have collaboration between countries in the global south that, in addition to adapting research to these populations, reduces the time to access to medicine”, says the director of the DNDI.

This is because when clinical research is authorized and monitored by the ethical committee and the regulatory agency of a country, all processes are faster: the presentation of results, their analysis, the discussion with the Ministry of Health, the recommendation.

“When research comes from outside, even if it has been approved by the WHO or by the American and European agencies, the regulatory agency will need to do its own analysis – which will start at the beginning and take longer”, says Sosa.

Brazilian research platform

The Brazilian group that participates in the ANTICOV consortium is Together Trial, an initiative by researchers from Minas Gerais that began in June 2020, initially to test drugs on patients in hospitals and which later evolved into tests on outpatients. Without obtaining funds in Brazil, the researchers obtained funding through a partnership with McMaster University, in Canada, and a grant from the University of Washington, in the USA.

The group was responsible for creating a protocol for clinical research against Covid-19 and for the Brazilian study that showed in October 2020 that hydroxychloroquine did not work in the treatment of Covid. The study was published in April 2021.

“The study was a success and we were requested by several international institutions, so we created a new platform, which was renamed Together Trial, for an adaptive study of drugs to treat the initial phase of Covid”, explains researcher Gilmar Reis, leader of research and professor of medicine at PUC-Minas.

“Instead of several studies, we have a platform that is a single study, with the same protocol, where drugs enter and leave”, says Reais.

Testing one of these drugs resulted in the publication of a paper in the renowned Lancet journal in October 2021.

The platform has already screened 25,000 people and had the participation of more than 6,000 patients. Their studies also showed the ineffectiveness of the use of metformin and ivermectin against Covid.

By joining ANTICOV, Together Trial will be responsible for carrying out the research of one of the arms of the consortium in Brazil. This new phase will begin by testing the effectiveness against Covid-19 of a new combination of drugs with anti-inflammatory action – both widely available, safe and already used in Brazil.

One of these substances that will be tested is of the same class as fluvoxamine, one of the drugs already tested by Together and whose research had positive results — but which has not yet been approved by Anvisa and is not indicated for use in patients.

“Fluvoxamine is an antidepressant drug that also has a mechanism of action that blocks the body’s inflammatory process,” explains Reis.

In many cases of Covid, the worsening of the condition is the result of an exaggerated immune reaction of the body – and this substance acts at the beginning of this process. The expectation is that the two drugs that will be tested together will also be able to stop this inflammatory process.

“Today, in July 2022, we know that the effect of reducing serious events of fluvoxamine is the same as that of the antiviral drug Molnupiravir, but no pharmaceutical company requested its approval from Anvisa. And we researchers are not going to submit this to Anvisa, our interest is not commercial. “

The new combination that will be researched by ANTICOV in Brazil will be tested in patients at the beginning of the disease, who are not hospitalized. The drugs are expected to reduce cases of aggravation and hospitalization, explains Reis. If the result is positive, the great advantage of the drugs is their price and availability.

It is not yet known whether the combination may also have the effect of reducing the incidence of the so-called “long Covid”, that is, when symptoms of the disease last for months in some patients.

“This is a central issue that still needs to be studied further.”

For Sergio Sosa, from DNDI, the inclusion of Brazilians in the research adds knowledge and technology and allows for consistency in the results.

“Isolated knowledge in science is not enough. It is important, but it is not enough. We seek to demonstrate consistency, which is the repetition of similar results by independent groups in different contexts”, he explains.

treatment and vaccine

Unlike vaccination, which is a preventive medicine and aims to prepare the body’s immune system to avoid contamination, drug treatments are administered during the development of the disease, after contamination. The goal is to fight the virus and prevent the disease from getting worse.

Treatments do not replace vaccination – according to Anvisa, vaccination remains the best way to avoid severe Covid-19, hospitalizations and deaths. Started in Brazil at the beginning of last year, it decisively changed the evolution of the pandemic, with a huge decrease in transmission, in severe cases and in the mortality of the disease.

However, treatments are still necessary, explains Reis, because “we still have an important contingent of people who, when acquiring Covid-19, even vaccinated, develop a severe inflammatory response, often interfere and often end up losing their lives.”

“Even in the vaccinated population, the mortality rate is still five or six times the mortality of Influenza (the flu virus). It is still a very serious disease”, he says.

In addition, the coronavirus has a great ability to mutate, and regions of the world where most of the population is not vaccinated serve as a place for the emergence of new strains.

Reis also explains that patients should not self-medicate with any of the drugs tested against Covid – and not even those approved by Anvisa, which must be indicated by doctors.

“Each drug is tested in a different scenario, works for certain audiences, and at different times in the development of the disease. The doctor’s indication is necessary, as they assess whether the patient fits into any of these situations”, highlights the researcher.

Treatments available against Covid-19 in Brazil

In most cases, treatment against Covid, explains the WHO, is done through palliative care of symptoms – and the body itself fights the virus and recovers from the disease. In cases of patients at risk, however, treatments against Covid-19 may be indicated that help to prevent the worsening of cases.

There are three types of drugs available today to treat Covid: antivirals, which make it difficult for the virus to reproduce inside the body; anti-inflammatories, which contain exaggerated and potentially lethal reactions from our immune system, and monoclonal antibody therapies, which mimic the immune system to attack the virus.

At the moment, there are six* drugs for treatment against Covid-19 approved by Anvisa:

• surrender – produced by the pharmaceutical company Gilead, it is an injectable antiviral for hospital use. It is intended in Brazil for patients with pneumonia who need oxygen supplementation, but who are not on artificial ventilation.
• paxlovid (nirmatrelvir + ritonavir) – oral antiviral from Wyeth/Pfizer, indicated as an early treatment for people at higher risk of having severe Covid-19. It should be taken as soon as possible within five days of symptom onset. The research that showed a high reduction in the hospitalization rate was done with unvaccinated people, so the patient should discuss with their doctor if there is an advantage for their case.
• molnupiravir – an antiviral from the pharmaceutical company MSD (Merck Sharp & Dohme), was the most recently approved drug. It must be indicated by a doctor and is mainly intended for patients with mild and moderate conditions and at risk of worsening. It should also be taken orally within five days of the onset of symptoms.
• Sotrovimab – GSK monoclonal antibodies for use only in hospitals. Indicated by Anvisa for people with mild to moderate Covid-19, but who are at risk of progression to the severe stage of the disease. In the British health service, it is often given as a transfusion to transplant recipients, cancer patients and other high-risk groups.
• baricitinib – anti-inflammatory recommended by the WHO for critically ill patients; and authorized by Anvisa for use in hospitalized adult patients who “need oxygen by mask or nasal catheter, or who require high flow oxygen or non-invasive ventilation”.
• Evusheld (cilgavimab + tixagevimab) – AstraZeneca injectable treatment with monoclonal antibodies indicated as prophylaxis (i.e. must be taken prior to exposure to Covid-19) for people with moderate to severe immune compromise or on immunosuppressant treatment. Anvisa highlights that prophylaxis with Evulshed does not replace vaccination for individuals in whom vaccination is recommended.

* three other drugs were approved, but their use was suspended or revoked.

Sources: Anvisa, WHO, NHS, GSK, MSD, Pfizer, Gilead, AstraZeneca.