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Remdesivir moves forward

In the midst of a major health emergency—widespread COVID-19—researchers were able to conduct a well-designed study of remdesivir vs. placebo. Here are some issues arising from this and other studies of remdesivir.

Remdesivir was able to hasten recovery from serious symptoms of COVID-19 by about four days vs. placebo. That is, participants who received remdesivir took about 11 days to recover vs. 15 days in people on placebo. There was a trend to reduced deaths among people on remdesivir—7% vs. 12% on placebo. However, this was not statistically significant. These results have caused doctors unaffiliated with the study to write an editorial in The New England Journal of Medicine noting that “the clinical effect of remdesivir was relatively modest.”

The benefit of treatment with remdesivir was seen mostly in people who entered the study with severe (but not critical) disease. In this subgroup, recovery occurred in 12 days among people who received remdesivir vs. 18 days among people who received placebo.

The doctors also underscored that people who entered the study with “mild-to-moderate disease” had a similar time to recovery (five days) as did people who received placebo.

The doctors stated that “remdesivir did not appear to improve outcomes in patients who required mechanical ventilation or extra corporeal membrane oxygenation [ECMO] but estimates of recovery require further follow-up in this group.” In ECMO, blood is withdrawn from the body, carbon dioxide is removed and oxygen is added, and then the blood is returned to the body.

It is important to note that the trial allowed participants to receive a range of other therapies. It will be important to analyse the data to assess any potential impact on recovery that these other therapies may have had.

Another study has compared two different courses of remdesivir—five vs. 10 days. As there was no placebo in that study, no overall evaluation of remdesivir could be made. However, either course of treatment seemed equally effective.

Analyses of subgroups of people in the placebo-controlled remdesivir study are needed in order to find out if there were differences in the response to therapy based on age, gender or ethno-racial group.

An evolving understanding

Infection with SARS-CoV-2 can cause a range of serious symptoms in some people. The virus appears to cause complications that affect different organ-systems, including the lungs, heart and blood vessels, brain, nervous system, kidneys, liver and the immune system. In some people this virus causes severe inflammation. Therefore, it is possible that a combination of drugs—antivirals and powerful anti-inflammatory agents as well as anti-clotting drugs—may be needed.

A sudden epidemic

SARS-CoV-2 was isolated about six months ago and it has spawned a worldwide pandemic. It normally takes at least several years to develop drugs specifically designed to treat an emerging virus and sometimes longer for an effective vaccine.

As a result of the sudden and widespread dissemination of SARS-CoV-2, existing medicines are being repurposed. Results from clinical medicines will not be ideal, as such medicines were not made to attack the new virus. Despite this, the effects of remdesivir are an important step forward. Here are some issues to consider about the future of remdesivir:

  • How early in the course of COVID-19 should remdesivir be initiated?
  • What other drugs are best combined with remdesivir?
  • Should antiviral and immune modulating drugs be initiated at the same time or should there be a sequence for the use of these drugs (one category before the other)?
  • Is intravenous administration the best way to administer remdesivir? Gilead has begun clinical trials of an inhaled formulation of this drug.
  • What will be the price of remdesivir?

—Sean R. Hosein

REFERENCES:

  1. Dolin R, Hirsch MS. Remdesivir - An important first step. New England Journal of Medicine. 2020; in press.
  2. Goldman JD, Lye DCB, Hui DS, et al. Remdesivir for 5 or 10 days in patients with severe Covid-19. New England Journal of Medicine. 2020; in press.
  3. Wang Y, Zhang D, Du G, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2020 May 30;395(10238):1694.
  4. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of Covid-19 – preliminary report. New England Journal of Medicine. 2020; in press.