May 26, 2020

expert reaction to announcement that remdesivir will be available to some patients via the Early Access to Medicines Scheme (EAMS)

The Department of Health and Social Care (DHSC) have announced that remdesivir will be available to some patients via the Early Access to Medicines Scheme (EAMS).

Professor Saad Shakir, Director of the Drug Safety Research Unit (DSRU) in Southampton, said:

“The MHRA decision is good for patients with Covid-19 in the UK.  Among all the drugs that have been tested so far, remdesivir is the only one that demonstrated efficacy in a double blind randomised clinical trial compared to placebo.

“It reduced the duration of illness from a median of 15 days to 11 (a reduction of 34%) which was statistically significant in patients who received remdesivir compared to those who didn’t. This is a clinically important effect.

“When the Data Safety management Board (DSMB) stopped the study because of this positive effect, the sample size was not large enough to examine the effect on mortality. A systematic benefit-risk evaluation conducted by the DSRU, which will be published this week, examined available data for the efficacy and safety of remdesivir, showed that it has a favourable effect in the treatment of patients with Covid-19 but acknowledged limited safety data. As results from more studies on remdesivir and data on its safety and effectiveness in real world usage become available, we will know more about the benefits and risks for this product.”

Prof Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine, said:

“The UK is now essentially outside the European system for regulation of medicines, but even prior to Brexit, the Early Access to Medicines Scheme was started. Its aim is “to provide earlier availability of promising new unlicensed medicines and medicines used outside their licence, to UK patients that have a high unmet clinical need.”

“It is important to realise that this allows for legal access to an unlicensed medicine. The amount of evidence on remdesivir’s efficacy and safety is still limited and it’s possible it will not become licensed. It is also not a recommendation for use, but it does allow clinicians to use the medicine outside one of the ongoing randomised trials without any fear of it being regarded as bad practise.

How does this change the situation in the UK and for which patients?

“Up to now, a doctor could not prescribe or use remdesivir, outside of an authorised randomised trial, without having the basis of any regulatory permission. It would be a situation where a doctor could not automatically offer a defence if things went wrong. Now it has this level of regulatory assessment, then it is seen as reasonable practice to prescribe it.  It is “for the treatment of adults and adolescent patients hospitalised with suspected or laboratory confirmed COVID-19 infection and severe disease”, so it is not for use in general practice nor for prevention of disease in those who do not have Covid-19. It is not for patients aged under 12.

How is this different to normal drug approval?

“This can be seen as a form of “provisional licence” as there are no drugs currently fully approved to treat patients with Covid-19 to deal with the virus causing that disease specifically (there are of course many drugs to treat symptoms caused by Covid-19). The amount of data to obtain a full licence has not yet been seen, and the approval is because there is unmet medical need. The approval lasts for a year but can be renewed.

Does this confirm that remdesivir works in treating patients? In what way does it help? Does it reduce mortality? 

“There is some evidence, but not as much as is usually required, that it works in dealing with the virus. The evidence is good that in these severely ill patients it reduces the time to recover. It seems to prevent the corona virus from reproducing itself. It probably works better when given early in the course of the disease. It may well reduce mortality, but the totality of evidence so far is not completely convincing on that, but with more trials being conducted around the world as well as in the UK, such evidence may be obtained soon.

What does this mean for remdesivir trials?

“It certainly encourages them to continue. It does not mean that other treatments will not be found, but it undoubtedly justifies the use of remdesivir in randomised trials. There are plenty of questions to which we still need answers, and the long-term effects have not been studied since COVID-19 has not be around more than 6 months and remdesivir-treated patients have not had 6 months’ follow-up.

Will it become a new standard of care in COVID-19? Should it?

“It’s a little too early to say it will become the standard of care. The large trials still ongoing should clarify that. Its availability in the UK and elsewhere is not yet clear. Its adverse effect profile is not fully understood, tough it seems there are as yet no major concerns.”

Prof Gino Martini, Chief Scientist at the Royal Pharmaceutical Society, said:

“There are a number of trials testing the efficacy of remdesivir against the virus which causes COVID 19. Some of these have been unsuccessful, but others such as the double-blind Adaptive COVID-19 Treatment Trial (ACTT-1) have showed that hospitalised COVID 19 patients recovered faster (median 4 days) than patients not receiving Remdesivir.

“This is why the MHRA  have allowed Remdesivir to be used in the UK for patients with high unmet medical need (determined by a doctor) through the Early Access Medicines Scheme (EAMS), where it will be provided to the NHS free of charge by Gilead throughout the EAMS period. It will also continue to be used in clinical trials.

“EAMS allows doctors and Gilead to collate real world evidence about the effectiveness of Remdesivir and its eventual authorisation if the drug is found help patients suffering with COVID 19.”

Dr Stephen Griffin, Associate Professor in the School of Medicine, University of Leeds, said:

“The news that Remdesivir will be available via the EAMS is welcome indeed. Remdesivir is perhaps the most promising direct-acting antiviral drug in current trials targeting COVID-19 and was recently given emergency approval by the FDA. The drug mimics the building blocks used by both our own cells and SARS-CoV2 to build new genomic material, yet it is only recognised by the viral machinery concerned with this process, so causing profound disruption to this essential viral process. Unlike many similar available antiviral drugs, remdesivir is also relatively unaffected by one of the safeguarding proteins that the virus uses to prevent this from happening, further boosting its importance for COVID19.

“Rolling out remdesivir via the EAMS will likely mean that the most severe COVID19 patients will receive it first. Whilst this is clearly the most ethically sound approach, it also means that we ought not to expect the drug to immediately act as a magic bullet. We can instead hope for improved recovery rates and a reduction in patient mortality, which we hope will benefit as many patients as possible. More pronounced benefit is likely to be seen when treating patients with less severe disease, ideally before they require invasive respiratory support, but this will only follow once the drug is more widely available and will be guided by the final outcomes of ongoing placebo-controlled trials. However, the necessity for intravenous administration means that the drug can only be given in a clinical setting, meaning that it unfortunately won’t be useful for disease prevention by prophylactic use amongst the wider population. Nevertheless, it should be recognised that the availability of remdesivir is a welcome boost to the current repertoire of COVID-19 therapies, and it could be important for the longer-term management of the pandemic.”

Press release – Selected NHS patients to access coronavirus treatment remdesivir: https://www.gov.uk/government/news/selected-nhs-patients-to-access-coronavirus-treatment-remdesivir

Press release – MHRA supports the use of remdesivir as the first medicine to treat COVID-19 in the UK: https://www.gov.uk/government/news/mhra-supports-the-use-of-remdesivir-as-the-first-medicine-to-treat-covid-19-in-the-uk

Early access to medicines scheme (EAMS) scientific opinion: Remdesivir in the treatment of patients hospitalised with suspected or laboratory-confirmed SARS-CoV-2 infection who meet the clinical criteria: https://www.gov.uk/government/publications/early-access-to-medicines-scheme-eams-scientific-opinion-remdesivir-in-the-treatment-of-patients-hospitalised-with-suspected-or-laboratory-confirme

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

Declared interests

Prof Saad Shakir: Saad Shakir is an employee of the Drug Safety Research Unit (DSRU), an independent charity (No. 327206), which works in association with the University of Portsmouth. He is a member of the Data Safety Monitoring Boards for Diurnal and Biogen. Gilead is providing support for a methodological project led by the DSRU as a part of a large group of pharma companies, unrelated to this product.

Prof Stephen Evans: No conflicts of interest.  I am funded (1 day/week) by LSHTM.  They get funding from various companies, including Astra Zeneca and GSK but I am not funded by them, I have no involvement in obtaining funding from them and I am not an investigator or any grants obtained from them.  I am the statistician to the “meta-Data Safety and Monitoring Board” for CEPI [https://cepi.net/].  I will probably be paid for my attendance at meetings and expenses for travel.

Prof Gino Martini: Gino has no interests to declare on this matter.

Prof Stephen Griffin: No conflicts