Covid-19 drug Remdesivir does not reduce death or hospital stay among patients, says WHO but Gilead disagrees
The drug is currently authorized for emergency use by the FDA for the treatment of hospitalized patients with coronavirus
A massive global study of potential drugs to treat Covid-19 suggests that Remdesivir — an antiviral drug developed by Gilead Sciences, Inc. — does not reduce deaths among hospitalized patients as compared to standard medical care. According to the World Health Organization (WHO), about 10.97% of coronavirus patients taking Remdesivir died in the clinical trial, versus 11.18% of patients receiving standard treatment.
The analysis looked at the effects of different treatments on overall death, initiation of ventilation and length of hospital stay in hospitalized patients. The interim results from the “Solidarity therapeutics trial,” coordinated by the WHO, indicate that Remdesivir, hydroxychloroquine, lopinavir/ritonavir, and interferon regimens appeared to have little or no effect on 28-day mortality or the in-hospital course of Covid-19 among hospitalized patients, suggests the agency.
“Remdesivir, hydroxychloroquine, lopinavir, and interferon regimens appeared to have little or no effect on hospitalized Covid-19, as indicated by overall mortality, initiation of ventilation and duration of hospital stay. The mortality findings contain most of the randomized evidence on Remdesivir and interferon, and are consistent with meta-analyses of mortality in all major trials,” concludes the WHO.
The results have been published on the preprint server medRxiv, which implies that it is yet to be peer-reviewed. According to WHO, the results of the trial are under review for publication in a medical journal. “In just six months, the world’s largest randomized control trial on Covid-19 therapeutics has generated conclusive evidence on the effectiveness of repurposed drugs for the treatment of Covid-19. Newer antiviral drugs, immunomodulators, and anti-SARS COV-2 (the virus that causes Covid-19) monoclonal antibodies are now being considered for evaluation,” it says.
Currently, Remdesivir is authorized for emergency use by the US Food and Drug Administration (FDA) for the treatment of hospitalized patients with coronavirus, irrespective of their severity of the disease. This emergency use authorization was given after a large clinical trial showed that the drug reduces the time it takes for Covid-19 patients to be discharged from the hospital, as compared with a placebo treatment. Remdesivir was also one of the drugs given to President Donald Trump after he was diagnosed with Covid-19.
A WHO-Covid-19 research forum in February 2020 recommended evaluation of treatments in large randomized trials and other WHO expert groups identified four re-purposed anti-viral drugs that might have at least a moderate effect on death: Remdesivir, hydroxychloroquine, lopinavir, and interferon. In March 2020, the agency began a large, simple, multi-country, open-label randomized trial among hospital inpatients to understand the effects of these four drugs on in-hospital mortality. Two drugs, hydroxychloroquine and lopinavir, were eventually dropped.
From March 22 to October 4, over 11,000 patients were entered from 405 hospitals in 30 countries in all 6 WHO regions. The analysis shows that 301 of 2,743 people hospitalized with Covid-19 taking Remdesivir died, compared with 303 of 2,708 people in the group getting standard care, indicating that Remdesivir did not have a survival benefit. “This absolutely excludes the suggestion that Remdesivir can prevent a substantial fraction of all deaths,” write authors.
Similarly, 104 out of 947 (10.98%) patients taking hydroxychloroquine died as against 84 out of 906 (9.27%) getting standard care. Further, 148 patients out of 1,399 (10.57%) who were given lopinavir died compared to 146 out of 1,372 (10.64%) receiving standard care. Further, out of 2,050 patients who got interferon, 243 died (11.85%), compared to 216 out of 2,050 (10.53%) who were given standard care.
All four drugs had little to no effect on reducing the length of hospital stay or the need for ventilation. “Death rate ratios were 0.95 for Remdesivir, 1.19 for hydroxychloroquine, 1.00 for lopinavir, and 1.16 for interferon. No study drug definitely reduced mortality (in unventilated patients or any other subgroup of entry characteristics), initiation of ventilation or hospitalization duration,” the findings state.
Dr Martin Landray, professor of medicine and epidemiology, Nuffield Department of Population Health, University of Oxford, called the results “important but sobering.” “Covid-19 affects millions of people and their families around the world. It is not a rare disease. We need scalable, affordable, and equitable treatments. The WHO Solidarity trial has done the world a huge favor by producing clear, independent and robust results, showing once more the value of large randomized trials in providing the knowledge we need to tackle the worst consequences of this pandemic,” explains Dr Landray, co-chief investigator of the Recovery trial, another large trial of potential treatments for Covid-19 being conducted in the UK.
Data is inconsistent, says Gilead
Stating that Gilead is aware that initial data from the WHO trial has been made public before publication in a peer-reviewed journal, the company said in a statement that the emerging data appear “inconsistent with more robust evidence” from multiple randomized, controlled studies published in peer-reviewed journals validating the clinical benefit of Remdesivir.
Gilead emphasizes that the benefits of Remdesivir have been demonstrated in three randomized, controlled clinical trials, including a randomized, double-blind, placebo-controlled clinical trial (ACTT-1), which it says is the “gold standard for evaluating the efficacy and safety of investigational drugs.”
The results from the National Institute for Allergy and Infectious Diseases (NIAID)’s ACTT-1 trial, which was conducted primarily in the US and Europe, found that treatment with Remdesivir resulted in “clinically meaningful improvements across multiple outcome assessments” in hospitalized coronavirus patients. The final results demonstrated that treatment with the drug resulted in a faster time to recovery than previously reported. Researchers found that patients taking Remdesivir recovered in 11 days on median, compared with a median of 15 days among patients receiving a placebo. In the final day 29 results, patients receiving Remdesivir achieved clinical recovery five days faster than those receiving placebo, with a median time to recovery of 10 days with Remdesivir and 15 days with placebo. About 11.4% of patients taking Remdesivir died after 29 days, compared with 15.2% taking the placebo.
“We are concerned that the data from this open-label global trial have not undergone the rigorous review required to allow for constructive scientific discussion, particularly given the limitations of the trial design. The Solidarity trial is a multi-center, open-label global trial that provided early access to Veklury (Remdesivir), among other investigational Covid-19 treatments, to patients around the world -- particularly in countries where ongoing trials of investigational treatments were not available. The trial design prioritized broad access, resulting in significant heterogeneity in trial adoption, implementation, controls, and patient populations and consequently, it is unclear if any conclusive findings can be drawn from the study results,” reads the statement.