What the clinical trial of an antiviral studied in phase II says to treat the first symptoms of COVID-19

The antiviral drug favipiravir is currently under investigation in the UK as a treatment for COVID-19 in people recovering at home and in other non-hospital settings, in a clinical trial funded and approved by the National Institute for Health Research.

With this antiviral, The researchers hope to treat the first symptoms of COVID-19, in order to avoid a more serious course of the disease and not to have to resort to hospitalizations.

The Randomized Platform Trial of COVID-19 Interventions in Older Adults (PRINCIPLE, funded by the University of Oxford) is one of those who have a national priority in the UK, and the largest in the world currently taking place in community settings.

This trial is evaluating a range of potential community treatments for COVID-19 to reduce recovery time and prevent hospitalizations and deaths. Favipiravir is the sixth drug in PRINCIPLE and the first antiviral drug.

As he assured in dialogue with Infobae the doctor of pharmacy and biochemistry Marcelo Peretta, “Favipiravir has been working in Asia for a long time. Many countries are seeking to prioritize the development of drugs used against influenza, for example to treat COVID. “

“The use of these antivirals is very important to reassure the population that when we present symptoms, we can treat it as quickly as possible to resume a normal life and go to work”, he concludes.

Favipiravir has been an antiviral drug authorized in Japan since 2014 to treat influenza.. It works by inhibiting a viral enzyme called RNA polymerase, preventing viral replication in human cells. This viral enzyme is common to several viruses, including SARS-CoV-2, which causes COVID-19.

Drug has shown positive results against SARS-CoV-2 in laboratory and animal studies, with small pilot trials in humans showing some benefit in reducing symptoms and duration of disease.

Co-principal investigator of PRINCIPLE, Chris Butler said: “Viruses need human cells to multiply and survive, and Favipiravir blocks the complicated molecular dance that occurs between a virus and our own cells when the virus replicates. This is the first drug we will test that has been specifically designed to target viruses, so we are particularly excited to include favipiravir in the trial to see if it could be used in the community as a treatment for COVID-19. and keep people from getting very sick. “.

Another ongoing trial is GETAFIX, in Glasgow, Scotland. If this drug proves effective against SARS-CoV-2, millions of doses will be distributed throughout the UK’s national healthcare system. The inspector Kevin Blyth, from the University of Glasgow, told the Mirror that “It would be a big step forward if this antiviral worked, because the health services would be less overwhelmed because patients would not have to go to the hospital.”

“Over the next six months we should definitely be able to get an answer. If this drug is effective, it may be able to reduce the spread and risk of epidemics, ”he added.

If GETAFIX Phase 2/3 trials show favipiravir to work, it could be the first antiviral treatment for mild COVID-19.

The Japan Trial

In Japan, although favipiravir was championed at the start of the pandemic as a promising drug for the treatment of COVID-19, Japanese regulatory authorities have not granted approval based on the phase III trial. In the favipiravir case study, the importance of a sound scientific evaluation of efficacy prior to drug approval was discussed.

Favipiravir, which prevents viral transcription and replication, was first approved in Japan in 2014 for the treatment of new or re-emerging pandemic influenza virus infections (limited to cases where other influenza antiviral drugs are ineffective).

As explained in an article published by scientists Munetaka Ueda, Tetsuya Tanimoto, Anju Murayama, Akihiko Ozaki and Masahiro Kami in the magazine American Society for Clinical and Therapeutic Pharmacology, the phase III trial undergoing regulatory approval at the time was a double-blind, randomized controlled trial designed to demonstrate the non-inferiority of oseltamivir in the treatment of influenza. However, it showed a statistically significant increase in the duration of illness in the favipiravir group. Therefore, Japan’s regulatory authority, the Pharmaceuticals and Medical Devices Agency (PMDA), has officially concluded that favipiravir has not been shown to be effective. Interestingly, given that infections with the highly pathogenic influenza virus can pose a threat to society, the drug was urgently approved on the condition that it would not be manufactured unless the Japanese Minister of Health, Labor and Welfare requests it.

However, in March 2020, after the declaration of the COVID-19 pandemic, several clinical trials with favipiravir were launched in Japan based on the efficacy observed in vitro against the severe acute respiratory syndrome coronavirus 2. (SARS-CoV-2). An application for a new conventional drug was filed in October 2020, when the results of the phase III study were finalized.

The data presented and the PMDA review report were discussed in December 2020 by the Pharmaceutical Affairs and Food Safety Council (PAFSC) of Japan, but it was concluded that regulatory approval should not be granted at this time and that continued review was required. The main problem was that the study was single-blind, despite the fact that the primary endpoint was the so-called soft endpoint, which included symptom relief and arbitrary assessment programs.

Critics have found that the biases between the two groups were too troublesome to confirm their effectiveness, although Fujifilm – the holding company behind its development – insisted that the study design be agreed with authorities before the study began. In any event, it was officially decided that the timeliness of approval would be determined on the basis of the upcoming results of ongoing clinical trials conducted in Kuwait and the United States, as data from only domestic clinical trials were insufficient.

However, Dr Reddy’s Laboratories, a company involved in the two overseas trials outside of Japan, announced on January 27, 2021 that it had ended the double-blind Phase III trial in Kuwait. This was due to an interim analysis of this trial, that 353 hospitalized patients with moderate to severe COVID-19 did not show a statistically significant difference for the primary endpoint between favipiravir and placebo. At the same time, the company said it will continue the pivotal Phase III study (PRESCO study) for COVID-19 patients with mild to moderate symptoms in the United States, with the aim of relieving symptoms and preventing disease progression. The PRESCO study is expected to include 826 patients and drug delivery to patients has started from December 2, 2020, with an interim analysis scheduled for the first half of 2021.

Fujifilm announced on Wednesday that it had started a new phase III trial in Japan of its drug Avigan (the name it gave to generic favipiravir) for COVID-19, reviving hopes for a local treatment of the virus.. The new, double-blind, placebo-controlled study targets patients aged 50 and older, as well as those at risk of developing serious illnesses, they reported in a statement.

KEEP READING: