First systematic benefit-risk assessment of Remdesivir published

29 May 2020

Remdesivir for COVID-19 patients is ‘favourable’ says first systematic benefit-risk study

We have just published the first ever systematic benefit-risk analysis of antiviral drug remdesivir for COVID-19 patients. The analysis found a ‘favourable’ profile overall, though there is currently limited safety data available.

The study was published on 28th May in the journal, Drug Safety, and recorded all possible benefits and risks for COVID-19 patients receiving remdesivir obtained by evaluating public data from peer reviewed journals and some pre-publication clinical trial data.

We found benefits of remdesivir including quicker recovery time, with one study showing median recovery time for remdesivir patients of 11 days compared with 15 days for those on a placebo. The analysis also found slight – though not statistically significant – reductions in mortality: 8% of remdesivir patients compared with 11.6% in patients given a placebo. Further benefits included reductions in the need for invasive and non-invasive ventilation and the need for supportive oxygen.

Due to the limited amount of clinical trial safety data, it is unclear whether reports of serious adverse events were caused by COVID-19, or the remdesivir treatment. Events included cardiovascular problems, such as cardiac arrest, hypotension and arrhythmias, as well as multiple organ dysfunction, septic shock, acute kidney injury, respiratory failure, liver enzyme issues and gastrointestinal events, including diarrhoea.

The conclusion of the benefit-risk assessment is that overall, the benefit-risk profile of remdesivir for COVID-19 patients was ‘favourable’ but that the study would need to be updated as more safety data became available.

Professor Saad Shakir, Director of the DSRU, says: “There is increasing interest in the use of medicines including remdesivir to treat patients with COVID-19 so it’s critical we understand the benefits as well as the risks of this re-purposed drug. Overall our study shows a favourable benefit-risk profile with the clinically significant benefit in reducing recovery time. But the paucity of safety data means we will need to keep reviewing and updating our benefit-risk analysis. To that end, we have designed a framework for our study that means we’ll be able to update it quickly as new data becomes available. Understanding the benefit-risk balance is key to understanding the benefits of drugs in general and drugs against COVID-19 in particular.”

Remdesivir was originally developed for the treatment of Ebola. Laboratory studies of cells and in animals have shown it is also active against coronaviruses SARS-CoV-2 (also known as COVID-19) and MERS-CoV. Several clinical trials on the effectiveness and safety of remdesivir for COVID-19 in people are ongoing and the US Food and Drug Administration (FDA) has now granted an Emergency Use Authorisation for remdesivir for COVID-19 patients. The European Medicines Agency has approved remdesivir for compassionate use in some patients with severe COVID-19 infection.

However, until this point there has not been a systematic benefit-risk assessment of the use of remdesivir for COVID-19 patients using a structured descriptive framework. We used the Benefit-Risk Action Team (BRAT) framework, which follows the structured format of a qualitative framework but allows flexibility in choice of quantitative assessment for the study. This analysis will be updated periodically as further information becomes known regarding the benefits and harms of remdesivir in the treatment of COVID-19.  The adaptable framework can be used to conduct rapid, structured evaluations of products (medicines and vaccines) and technologies proposed to treat COVID-19.

The pre-publication version of this benefit-risk analysis was provided to the MHRA (the UK medicines regulator) before regulatory approval was issued this week for use of remdesivir for certain severely infected patients.

The DSRU has also completed the first systematic benefit-risk evaluation for chloroquine/hydroxychloroquine and ritonavir/ lopinavir in COVID-19, which have been submitted for publication.

The full study paper is now available in the journal Drug Safety at the following link: https://link.springer.com/content/pdf/10.1007/s40264-020-00952-1.pdf