Company pushes back on findings from open-label trial

A pre-publication copy of findings from the World Health Organization’s SOLIDARITY trial, which tested the efficacy of repurposing antiviral drugs such as remdesivir to treat Covid-19, rattled the drumbeat of enthusiasm for remdesivir with the finding that it did not significantly reduce Covid-19 mortality or hasten recovery.

The SOLIDARITY trial reported uniformly null results for all tested treatments:

“In 405 hospitals in 30 countries 11,266 adults were randomized, with 2,750 allocated remdesivir, 954 hydroxychloroquine, 1,411 lopinavir, 651 interferon plus lopinavir, 1,412 only interferon, and 4,088 no study drug. Compliance was 94-96% midway through treatment, with 2-6% crossover. 1,253 deaths were reported (at median day 8, IQR 4-14). Kaplan-Meier 28-day mortality was 12% (39% if already ventilated at randomization, 10% otherwise). Death rate ratios (with 95% CIs and numbers dead/randomized, each drug vs its control) were: Remdesivir RR=0.95 (0.81-1.11, P=0.50; 301/2743 active vs 303/2708 control), hydroxychloroquine RR=1.19 (0.89-1.59, P=0.23; 104/947 vs 84/906), lopinavir RR=1.00 (0.79-1.25, P=0.97; 148/1399 vs 146/1372) and interferon RR=1.16 (0.96-1.39, P=0.11; 243/2050 vs 216/2050). No study drug definitely reduced mortality (in unventilated patients or any other subgroup of entry characteristics), initiation of ventilation, or hospitalization duration.”

The remdesivir findings stood in marked contrast to findings from the National Institute of Allergy and Infectious Diseases sponsored ACTT-1 trial, which found a benefit for remdesivir, the only antiviral treatment that is FDA approved — under an emergency use authorization — for treatment of Covid-19. Remdesivir was one of the drugs given to President Donald J. Trump as part of his treatment for Covid-19.

WHO defended the trial noting that SOLIDARITY was an open-label trial that offered broad access to the drug to a heterogeneous group of patients. As such, the trial provided fast answers that were urgently needed, WHO argued.

In a statement, remdesivir maker Gilead said remdesivir’s benefits “have been demonstrated in three randomized, controlled clinical trials, including a randomized, double-blind, placebo-controlled clinical trial (ACTT-1) – 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 United States and Europe, found that treatment with [remdesivir] resulted in clinically meaningful improvements across multiple outcome assessments in hospitalized Covid-19 patients. These data were peer-reviewed and published in the New England Journal of Medicine and have supported [remdesivir’s] inclusion in multiple treatment guidelines. These data have also supported regulatory approvals or temporary authorizations to treat Covid-19 in approximately 50 countries worldwide. Additionally, we are pleased that today WHO has prequalified remdesivir, which assures procurement agencies such as the United Nations that [remdesivir] has met global standards of quality, safety, and efficacy.”

NEJM reported that “Kaplan–Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03).

Reaction to Friday’s release of the pre-publication copy of SOLIDARITY findings was swift, as the New York Times reported:”This puts the issue to rest — there is certainly no mortality benefit,” said Dr. Ilan Schwartz, an infectious disease physician at the University of Alberta in Canada.

Peggy Peck, Editor-in-Chief, BreakingMED™

Cat ID: 190

Topic ID: 79,190,190,31,926,192,927,151,725,928,925,934