Since the beginning of the covid-19 pandemic, the world has been searching for a drug that people can take at home and avoid the risk of complications from the disease. At first, an attempt was made to reposition existing drugs for other purposes, but none was effective.
Now, this search may be nearing its end, as the final phase of clinical trials of the antiviral advances. molnupiravir.
The drug was invented by a nonprofit US biotechnology company—Drug Innovations at Emory—which receives partial funding from the US government.
Later, the formula was licensed by the company Ridgeback Biotherapeutics, based in Florida, which signed an agreement with the pharmaceutical company MSD (Merck Sharp & Dohme) to enable the clinical studies and production.
You tests advanced to phase 3 in April of this year, after promising results in volunteers who used the drug in the first days since the onset of symptoms.
With around 1,800 volunteers still being recruited around the world, even in Brazil (see research centers below), MSD expects to have interim results from this phase by October.
The expectation of the pharmaceutical is that the final data for obtaining registration are presented to regulatory agencies this year.
“What we have today is the phase 3 study right in the patient population at the onset of illness — up to five days of symptoms, not hospitalized. They take 800 mg, twice a day for five days. It’s this anti-treatment arm. the placebo [substância sem efeito terapêutico] to be able to prove the effectiveness of what we’ve seen in phase 1 and 2 studies. […] What we want to prove now is that there is a reduction in hospitalization and death”, explains the medical director of MSD Brazil, Marcia Abadi.
Treatments such as monoclonal antibodies and the antiviral remdesivir have restrictions on their use — they are restricted to hospitals and a certain patient profile — and on their price, as they cost a few thousand reais.
In this context, a possible success of molnupiravir may be what oseltamivir (Tamiflu) was during the 2009 H1N1 pandemic. To date, the drug is prescribed when influenza virus infection is suspected, especially in more vulnerable individuals such as children and elderly.
According to Professor Alexandre Naime Barbosa, head of infectology at Unesp (State University of São Paulo) in Botucatu, if molnupiravir proves to be effective in the first symptoms of covid-19, it can be used to increase protection in vulnerable individuals.
“How much is my individual chance of protection with vaccines? Between 80% and 90% reduction in hospitalization and death. If I had an effective medication in the initial days, I could go up to a protection between 95% and 97%, which In fact, you can already see the example. It happens with the flu. I vaccinate elderly people, for example, but if there is a patient with the flu syndrome and is from a risk group, I use oseltamivir in the first 48 hours. , timing is everything.”
How it works
Molnupiravir focuses on the genetic material of RNA viruses, such as SARS-CoV-2, which causes covid-19.
By attacking the coronavirus genome, the drug prevents it from reproducing within the organism of the infected person, which consequently prevents the disease from worsening.
The researchers also observed an ability of molnupirvir to reduce the viral load in the nasopharynx and eyes of people exposed to the coronavirus.
MSD’s medical director says the 800 mg dose has been shown to be safe and effective in tests.
“What we saw in the initial studies is that the side of adverse events is equivalent to placebo, that is, it has an absolutely tolerable safety profile, which is very important.”
Capsule presentation, like any other drug we buy in pharmacies, also counts positively in favor of molnupirvir over the intravenous infusions available today, as it facilitates distribution and use.
When MSD obtained the phase 2/3 interim data at the end of April, it chose to start producing the equivalent of 10 million treatments.
On June 9, the US government closed an intent-to-purchase agreement with MSD for approximately 1.7 million treatments once molnupiravir receives emergency use authorization or definitive registration from the FDA. Drugs and Food in the country).
Marcia points out that the production was “at risk”, but with the intention of having the remedies available immediately if requests with regulatory bodies are approved.
According to the executive, having volunteers in Brazil is a facilitator to obtain authorization from Anvisa (National Health Surveillance Agency).
“If everything works out, if the study proves its results, we intend to talk as soon as possible with the regulatory agencies. Here in Brazil [será] almost concurrently with international regulatory agencies. […] Here in Brazil, our expectation is to have access to this medication in a broad way.”
The pharmacist must put a good part of its industrial park and global capillarity in the production and distribution of the medicine, he adds.
Clinical trials have suggested yet another potential use for molnupiravir: post-exposure prophylaxis.
Based on these findings, MSD announced on March 1 a second phase 3 study to see if there is an advantage in people who have been exposed to the virus taking the drug even before they develop any symptoms.
The Unesp professor exemplifies a case in which post-exposure prophylaxis would be useful.
“I attended a 90-year-old lady who lives with her daughter and grandson. The grandson is not following the prevention issues properly and ended up becoming symptomatic and passing the covid on to his mother and grandmother. Luckily, they are vaccinated. and they had a moderate covid, there was no need to be hospitalized for now. But if I had conclusive studies showing the effectiveness of this medication, I could have done it [tratamento preventivo] soon after discovering the infection in the boy. The 90-year-old grandmother would be a potential beneficiary.”
Marcia says it is possible that there are also volunteers for this arm of the study here in Brazil. In all, there must be about 1,300 volunteers.
Persons aged 18 years or older and living in the same household as someone who has laboratory-confirmed SARS-CoV-2 infection with symptoms will be eligible.
Volunteers will receive 800 mg of molnupirvir or placebo (without knowing what they are taking) every 12 hours for five days.
Individuals over the age of 18 who have been diagnosed with covid-19 for less than five days can go to one of the addresses below to apply to volunteer for testing for molnupiravir. Everyone will be instructed about the treatment and will sign an informed consent form.
São Paulo (Capital)
1) Clinical Research Center of Hospital das Clínicas
Rua Doutor Ovídio Pires de Campos, 555, 6th floor – CeAC Building – Employee Assistance Center – Cerqueira César
2) Institute of Infectology Emílio Ribas
Av. Dr. Arnaldo, 165 – Cerqueira César
São Paulo (Interior)
3) Base Hospital of São José do Rio Preto (São José do Rio Preto)
Av. Brigadeiro Faria Lima, 5544 – Vila São Jose, São José do Rio Preto
4) Santa Casa da Misericórdia of Belo Horizonte
Av. Francisco Sales, 1111 – Santa Efigênia, Belo Horizonte
5) Hospital das Clínicas of the Federal University of Paraná (Curitiba)
Rua Padre Camargo, 261 – Alto da Glória
Rio Grande do Sul
6) Hospital Tacchini (Bento Gonçalves)
Rua General Osório, 235, basement 2
7) Clinical Research Chronos
Avenida Helio Prates QNM 34 A/E 01 JK Shopping Tower Sala – 612/613 – Taguatinga Norte