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Source: United Kingdom – Executive Government & Departments

The US Food and Drug Administration has provided Emergency Use Authorisation for the drug remdesivir to be used on hospitalised patients with COVID-19 in the US.

Prof Derek Hill of UCL, an expert in medicine and medical device regulation, said:

“The FDA regulates medicines to ensure they are safe and effective for use on patients.  Because a high level of scientific evidence is required, alongside detailed documentation of everything that was done in the clinical trials, drug approval is a long and slow process. Getting approval for a new medicine to be used on patients normally takes many years and on average costs well over $1bn.  However, within its regulatory framework, the FDA has special arrangements in time of chemical, biological, radiological, nuclear (CBRN) and emerging infectious disease threats.  In such times of public health emergency, the FDA can therefore dramatically speed up the time taken to make a medicine available.

“This highly streamlined process is not the same as approval. It is an “Emergency Use Authorization” (EUA).   Remdesivir has now received this emergency use authorization so can be used on severely ill, hospitalised COVID-19 patients.

“This is done as a result of the preliminary data from the US government run trial that published preliminary results earlier this week.  There is nothing like sufficient data to justify a drug approval, but the FDA has decided that under these extraordinary circumstances, remdesivir may be used on COVID patients entirely legally. That authorization means that Gilead can invest in ramping up production to make sufficient medicine available for use on patients.

“Remdesivir is not a cure for COVID-19. There is evidence from the preliminary analysis that it speeds up patient recovery. There is a hint in the data that it may also reduce mortality, but that result was not statistically significant, so is quite likely to be a chance finding.  When more data is available, this may tell us whether or not remdesivir can save lives as well as speed up recovery.  More data may also help determine whether or not remdesivir can improve recovery for more mild COVID-19  patients who are not hospitalised.  At the moment, the EUA is just for severely ill, hospitalized patients.

“The FDA has no jurisdiction in the UK or the rest of Europe, so this EUA does not enable remdesivir to be used here.”

Prof Stephen Evans, Professor of Pharmacoepidemiology in the Dept of Medical Statistics, London School of Hygiene & Tropical Medicine, said:

“The US Food and Drug Administration (FDA) has issued an Emergency Use Authorization for the anti-viral drug remdesivir for use in hospitalized patients with Covid-19.

“included allowing the FDA to bypass the usual procedures for assessment of efficacy and safety of medicines and to allow use of otherwise unapproved medicines to be used to treat Covid-19.

– What does approval for emergency use mean?

“The key element is that “There is no adequate, approved, and available alternative to the emergency use of remdesivir for the treatment of COVID-19.”. It sets out the conditions under which remdesivir may be distributed and used. It does not allow Gilead to market the drug. In this case it allows doctors to obtain and use the drug in hospitalized patients with known or suspected severe Covid-19 and who require at least supplemental oxygen. The doses are set out and it must be injected in a hospital.

– How is this different to normal drug approval?

“This means that the usual processes of assessment of efficacy, safety and quality are bypassed. There is a very basic check that there is some evidence of efficacy and that there are no known serious harms that outweigh the potential benefits. In this case the large (probably 800-100 patients) multi-national trial sponsored by the US National Institute of Allergy and Infectious Diseases (NIAID) has preliminary results showing convincing benefit in time to recovery of about 4 days. However very few details are available about the results though there is a suggestion, though not convincing, that mortality is also improved.

“This is almost unprecedented, since Gilead, the manufacturer, has not carried out the trial and has only conducted trials that involved remdesivir alone. It is relying on others to conduct trials with a comparison group that does not have remdesivir, which is the only way to provide convincing evidence of the drug’s efficacy and lack of harm.

“It is possible that further data from randomised trials will be submitted to the FDA and other regulators around the world at a later date to try and obtain approval for marketing the drug, but it is speculated that may never happen if its use is sufficient in the absence of the normal marketing approval process. The usual process would require another separate trial also showing convincing evidence of efficacy and safety before approval would be given.

– Why had the FDA done this?

“Gilead had approached the FDA requesting this, supplying their own data from trials they had conducted without a remdesivir group, and presumably they had been provided the NIAID trial data which have not been made public. It is obvious that there is an emergency with large numbers of patients dying in spite of the best efforts of doctors, and there are no drugs which have even reasonable evidence that they work. The NIAID trial does provide good evidence, based on fairly large numbers, that the time to recovery is improved and mortality may be improved, certainly not made noticeably worse.

– Is it warranted by the evidence?

“We do not really know. The main evidence has only been made public in a brief press release that does not even state how many patients were studied. The estimate of the numbers included were calculated by me on making various assumptions about the minimal data that were provided. Some concerns have been expressed about changes in the primary outcome studied, which may not be well-founded concerns, but the absence of information does not allay them.

The well-conducted trial from China and fully published in The Lancet [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31022-9/fulltext] was too small to draw conclusions, and while compatible with the results shown in the NIAID trial, taken together they show the evidence of efficacy may not be quite as great as shown in the NIAID trial on its own. In addition, there is another Chinese trial, also stopped because the numbers of new patients with Covid-19 had fallen in China so they were unable to recruit, which has not yet published its data. There are other trials where remdesivir is compared with non-remdesivir treatments currently been done and results from some of these should appear soon. A wider view will give a better understanding of the benefits and harms with remdesivir, but in this emergency, it is not totally unreasonable of the FDA to allow for its use, but it would undoubtedly have been better to provide more of the evidence in public.”

 

Dr Michael Head, Senior Research Fellow in Global Health, University of Southampton, said:

“The ‘approval for emergency use’ refers to rapid approvals of drugs by the US FDA during public health emergencies. This is done here because COVID-19 is caused by a high-threat pathogen with very limited treatment options. Remdesivir has shown some effectiveness in clinical trials, and so may be useful as a treatment option, in addition to usual packages of care. It’s use at the moment is limited to hospitalised patients (so not available ‘over the counter’).

“This is an important step in options available to clinicians to treat those hospitalised with COVID-19. The data shows that many hospitalised patients will die, so although the effectiveness of remdesivir is limited, it may be a useful addition as an option for treatment. The drug was designed for addressing Ebola, but there was little effectiveness in clinical trials. However, that research has given us knowledge around drug safety and toxicity that can be applied to research and treatments here with COVID-19. It shows the importance of exploring the use of existing therapeutics when new pathogens emerge.”

https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-issues-emergency-use-authorization-potential-covid-19-treatment

All our previous output on this subject can be seen at this weblink: www.sciencemediacentre.org/tag/covid-19

Declared interests

Prof Stephen Evans: No conflict of interest

None others received.

MIL OSI United Kingdom