Press Release courtesy of BusinessWire.
The New England Journal of Medicine(NEJM) today published the final results from the National Institute of Allergy and Infectious Diseases’ (NIAID) double-blind, placebo-controlled, Phase 3 ACTT-1 trial of Gilead’s (Nasdaq: GILD) investigational antiviral Veklury® (remdesivir) for the treatment of adults hospitalized with mild-moderate or severe COVID-19. The final ACTT-1 study results build on the preliminary results published in NEJM in May 2020, showing that treatment with Veklury resulted in consistent, clinically meaningful improvements across multiple outcome assessments compared with placebo in COVID-19 patients. The final results demonstrate that treatment with Veklury resulted in a faster time to recovery than previously reported.
In the preliminary Day 15 results, Veklury plus standard of care shortened the time to recovery by four days, compared with placebo plus standard of care (11 vs. 15 days). The primary endpoint of the study was time to clinical recovery through Day 29. The study met its primary endpoint, demonstrating Veklury plus standard of care was superior in shortening the time to recovery through Day 29 compared with placebo plus standard of care. In the final Day 29 results, patients receiving Veklury (n=541) achieved clinical recovery five days faster than those receiving placebo, with a median time to recovery of 10 days with Veklury and 15 days with placebo and an increased recovery rate by 29 percent compared with placebo (rate ratio for recovery, 1.29; 95% confidence interval [CI], 1.12 to 1.49; p<0.001). This result was most pronounced in patients who required oxygen support at baseline (n=957); in this group, patients receiving Veklury achieved clinical recovery seven days faster than those receiving placebo, with a median time to recovery of 11 days with Veklury and 18 days with placebo (rate ratio for recovery, 1.31; 95% CI, 1.12 to 1.52).
The key secondary study endpoint of clinical status at Day 15 was also met. Patients receiving Veklury were 50 percent more likely to have improved by Day 15 compared with those receiving placebo (OR, 1.5; 95% CI, 1.2 to 1.9), and the effect was maintained through Day 29. The benefit of Veklury was greater when given within 10 days of symptom onset, though benefit was observed across most ranges of symptom duration.
In the overall study population, there was a trend toward reduced mortality, a secondary study endpoint, at Day 15 (6.7% vs. 11.9%; HR, 0.55; 95% CI, 0.36 to 0.83) and Day 29 (11.4% vs. 15.2%, HR 0.73; 95% CI, 0.52 to 1.03) in Veklury-treated patients compared with placebo. Given the range of disease severity in the overall study population, a post-hoc analysis with no adjustment for multiple testing was conducted to determine whether there were differences in mortality based on patients’ baseline clinical status and to better understand where Veklury may have the most benefit. In this analysis, patients requiring low-flow oxygen at baseline who received Veklury achieved a statistically significant 72 percent reduction in mortality at Day 15 (3.1% vs. 10.5%; HR, 0.28; 95% CI, 0.12 to 0.66) and a statistically significant 70 percent reduction in mortality at Day 29 (4% vs. 13%; HR, 0.30; 95% CI, 0.14 to 0.64). The difference in mortality in other subgroups based on baseline clinical status was not statistically significant.
“The ACTT-1 trial results demonstrate that in hospitalized patients with COVID-19 pneumonia, remdesivir is the first antiviral medication significantly associated with a shorter time to recovery—five days shorter for all patients and seven days shorter for the more severely ill patients—in combination with a lower progression to mechanical ventilation,” said Andre Kalil, MD, MPH, Professor of Internal Medicine, Division of Infectious Diseases, Director, Transplant Infectious Diseases Program at the University of Nebraska Medical Center, and a principal ACTT-1 trial investigator. “Based on clinical experience, we have seen that patient response and mortality risk differ across the disease spectrum. With this mortality subgroup post-hoc analysis, we now have data suggesting that giving remdesivir to patients on oxygen may significantly reduce their chances of death as compared to other subgroups. These data provide clinicians with important information to help optimize patient care.”
Other secondary endpoints including time to discharge, oxygen use, and incidence and duration of new oxygen use or other respiratory support, were also met. Patients in the Veklury treatment group had a shorter time to discharge or National Early Warning Score of ≤ 2 compared with placebo, with a median time to discharge or NEWS ≤ 2 of 8 days with Veklury and 12 days with placebo (HR, 1.27; 95% CI, 1.10 to 1.46). Veklury reduced disease progression among those who received the investigational antiviral, resulting in fewer median days on oxygen support (13 days vs. 21 days) and a significantly lower incidence of new ventilation or ECMO (13%; 95% CI, 10% to 17%) compared with those on placebo (23%; 95% CI, 19% to 27%).
“There is a critical need to generate data that can help healthcare providers make informed treatment decisions and offer their patients the best chance at recovery. These data from a rigorous, double-blind, placebo-controlled trial add to the breadth of evidence from additional randomized clinical trials supporting the use of Veklury as a standard of care for the treatment of COVID-19 in hospitalized patients,” said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. “The robust evidence on the clinical benefits of Veklury, coupled with significantly expanded global supply, puts an important treatment option in the hands of healthcare providers around the world.”
Overall, the incidence of adverse events associated with Veklury was similar to placebo, with no new safety signals identified as compared to the interim analysis. Rates of serious adverse events (SAEs) were numerically higher in the placebo group compared with the Veklury group (PBO + SOC: 32%; Veklury + SOC: 25%). Treatment discontinuation, all cause grade 3 and 4 adverse events and laboratory abnormalities were similar across groups.
