Interim results from the Solidarity Therapeutics Trial, coordinated by the World Health Organization, indicate that none of the four treatments in the trial, which enrolled more than 11,000 patients in 400 hospitals around the globe, definitively increased survival.
The world’s largest randomized control trial on COVID-19 therapeutics found 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. The study, which spans more than 30 countries, looked at the effects of these treatments on overall mortality, initiation of ventilation, and duration of hospital stay in hospitalized patients.
Death rate ratios (with numbers dead/randomized, each drug vs its control) were: Remdesivir RR=0.95 ( 301/2743 active vs 303/2708 control), Hydroxychloroquine RR=1.19 (104/947 vs 84/906), Lopinavir RR=1.00 (148/1399 vs 146/1372) and Interferon RR=1.16 ( 243/2050 vs 216/2050).
Hope had faded for two of the prospects — the malaria drug hydroxychloroquine and the HIV drug combination ritonavir/lopinavir — following the results of previous studies.
On June 15, the FDA revoked the prior emergency use authorization (EUA) it had granted to hydroxychloroquine on March 28 following poor clinical HCQ data. Later that month, the NIH halted its blinded, placebo-controlled randomized clinical trial of HCQ after its data and safety monitoring board concluded that the drug does no harm, but was very unlikely to be beneficial to hospitalized patients with COVID-19.
AbbVie's HIV-1 drug Kaletra (lopinavir/ritonavir) had been proposed as a treatment for COVID-19 on the basis of in vitro activity, preclinical studies, and observational studies — but subsequent studies did not point to effectiveness. Early on in the pandemic, AbbVie garnered praise for announcing it would no longer enforce patents relating to Kaletra anywhere in the world for all formulations.
There was still hope for remdesivir and for interferon-beta, however.
Interferons, which are antiviral proteins produced by the body as a natural defense against viral infections, were tested in synthetic form as a possible means of preventing or treating the beginning stages of SARS-CoV-2 infection. Interferons were initially tested in combination with ritonavir/lopinavir in an NIAID trial, but later tested as a standalone drug.
Gilead's remdesivir, which attacks a specific enzyme in several RNA viruses and previously failed in testing against Ebola, has been seen as a promising candidate. The drug received EUA from the FDA in May for severe COVID-19 patients that was later expanded to include all patients. The drug was thrust back into the headlines after it was revealed that President Trump received it following his positive COVID diagnosis. The drugmaker has been ramping up production of the investigational antiviral, now called Veklury, by making significant investments to increase internal manufacturing capacity and expand contract manufacturing. Gilead submitted a new drug application for Veklury on August 7, 2020; the NDA is currently under FDA review.
The remdesivir Solidarity findings conflicted with findings from the NIAID sponsored ACTT-1 trial, which found a benefit for remdesivir. The drugmaker released a statement in response to the Solidarity trial results, saying, "The emerging data appear inconsistent with more robust evidence from multiple randomized, controlled studies published in peer-reviewed journals validating the clinical benefit of Veklury."
Scientists at the World Health Organization released the trial data as a preprint on medRxiv, ahead of its planned review for publication in The New England Journal of Medicine.
Read the WHO press release
Read the AAAS analysis