Remdesivir Fails to Benefit COVID-19 Hospitalization, Death in WHO Study

Interim results from the ongoing World Health Organization (WHO) Solidarity Trial show remdesivir has provided little to no benefit for patients hospitalized with coronavirus 2019 (COVID-19), on metrics of overall mortality, ventilation need, and duration of hospital stay.

The findings come a week after results from the ACTT-1 and ACTT-2 trials indicated the antiviral therapy—both alone and in combination use—were associated with reduced time to recovery and mortality risk versus placebo among hospitalized COVID-19 patients.

It also comes 2 weeks following President Trump’s hospitalization, during which he began a five-day regimen of remdesivir plus corticosteroid dexamethasone, along with an investigative monoclonal antibody cocktail—giving the Gilead therapy a national media spotlight.

But these newest reported findings from WHO—in a robust, real-world, global series of randomized trials for 4 antiviral drugs in patients hospitalized for COVID-19—indicated minimal benefit with remdesivir. Similar outcomes were observed for the Solidarity Trial’s 3 other assessed agents: hydroxychloroquine, lopinavir, and interferon.

“The main outcomes of mortality, initiation of ventilation and hospitalization duration were not clearly reduced by any study drug,” investigators wrote. “Although ACTT-1, with placebo control, reported remdesivir moderately reduced time to recovery, in the present study there were no material effects on ventilation initiation or time to discharge.”

The Solidarity investigators randomized COVID-19 patients equally between whichever of the 4 study drugs were locally available and open control: remdesivir, hydroxychloroquine, lopinavir fixed-dose combination with ritonavir, and subcutaneous interferon-β1.

They compared study drugs versus control, with an intent-to-treat primary analysis of in-hospital mortality, as per unstratified Kaplan-Meier 28-day risks and age- and ventilation-stratified log-ran death rate ratios (RRs).

Their findings included 11,266 adults randomized to remdesivir (n = 2750), hydroxychloroquine (954), lopinavir (1411), interferon plus lopinavir (651), lone interferon (1412), or no study drug (4088). Investigators observed a compliance rate between 94-96% through treatment.

The team reported 1253 (11.1%) deaths, at a median duration of 8 days (IQR, 4-14). The unstratified Kaplan-Meier 28-day mortality was 12%; it spiked to 39% among patients ventilated at the time of randomization.

Death rate ratios were consistently underwhelming for each observed regimen:

• Remdesivir RR, 0.95 (95% CI, 0.81 – 1.11; P = .50)
• Hydroxychloroquine RR, 1.19 (95% CI, 0.89 – 1.59; P = .23)
• Lopinavir RR, 1.00 (95% CI, 0.79 – 1.25; P = .97)
• Inferferon RR, 1.16 (95% CI, 0.96 – 1.39; P = .11).

Investigators observed no definite reduction of mortality, initiation of ventilation, nor hospitalization duration with any of the studied therapies.

The infectious disease community responded with disappointment to the newest Solidarity findings—particularly for remdesivir, which to a point has served as a viable option for patients severely ill with COVID-19.

Jason Pogue, PharmD, BCPS, BCIDP, clinical pharmacist and professor in infectious diseases at the University of Michigan College of Pharmacy, told Contagion® there is “no way around” these newest findings.

“This is a very disappointing result,” he said. “It really throws into question what role, if any, remdesivir has in the management of hospitalized patients with COVID-19, particularly at its current price point.”

The Solidarity trial will continue to recruit and assess an additional 2000 hospitalized patients with COVID-19 monthly. Investigators hope to progress toward assessment of immunomodulators and specific SARS-CoV-2 targeting monoclonal antibodies. The hope is now to improve on the minimal impact by remdesivir, hydroxycholoroquine, lopinavir, and interferon.

“The unpromising overall findings from the regimens tested suffice to refute early hopes, based on smaller or non-randomized studies, that any will substantially reduce inpatient mortality, initiation of ventilation or hospitalisation duration,” they wrote. “Narrower confidence intervals would be helpful (particularly for remdesivir), but the main need is for better treatments.”