The final results of a trial investigating remdesivir for the treatment of coronavirus disease 2019 (COVID-19) has found that the drug shows superior efficacy compared with a placebo, resulting in a 5-day faster recovery and reduced disease progression.

The results, published in The New England Journal of Medicine, are from the National Institute of Allergy and Infectious Diseases’ double-blind, placebo-controlled, phase 3 trial. In the preliminary day 15 results published in May, remdesivir plus standard of care was found to shorten the time to recovery by 4 days compared with the placebo plus standard of care.

The study met its primary endpoint of time to clinical recovery through day 29, demonstrating that remdesivir was superior in shortening the time to recovery. In the final results, 541 patients treated with remdesivir achieved a median time to recovery of 10 days compared with 15 days in patients given a placebo, and a 29% increased recovery rate.

In an open letter, Gilead Chairman and CEO Daniel O’Day, MBA, said that patients with severe disease recovered 7 days faster on average. These patients with severe disease comprised 85% of the total study population, according to the letter.

“For patients who are hospitalized with COVID-19, the importance of speeding up recovery by 5 to 7 days cannot be underestimated,” O’Day said in the letter. “Aside from the physical challenges, every day with the disease brings an emotional toll on patients and their families dealing with the separation and the worry.”

The study also met its secondary study endpoint of clinical status at day 15, with patients in the remdesivir arm 50% more likely to have improved by day 15 compared with those receiving the placebo and the effect was maintained through day 29. The benefit of remdesivir was greater when given within 10 days of symptom onset, although the authors said benefits were observed across most ranges of symptom duration.

Investigators observed a trend toward reduced mortality in the overall study population at day 15 and day 29 in patients treated with remdesivir. In a post-hoc analysis with no adjustment for multiple testing, researchers found that patients requiring low-flow oxygen at baseline who received remdesivir achieved a 72% reduction in mortality at day 15 and a 70% reduction in mortality at day 29. The difference in mortality in other subgroups based on baseline clinical status was not statistically significant, according to the press release.

Finally, the study also met other secondary endpoints, including time to discharge, oxygen use, and incidence and duration of new oxygen use or other respiratory support. Patients receiving remdesivir had a shorter time to discharge compared with those receiving the placebo, with a median time of 8 days with remdesivir and 12 days with the placebo. They also had a significantly lower incidence of new ventilation compared with those on the placebo.

“In addition to the direct impact on patients, these outcomes represent clear benefit and value to health care systems,” O’Day wrote. “Remdesivir could help to lower the use of health care resources and reduce the number of days that patients are in the hospital.”

The incidence of adverse events (AEs) associated with remdesivir was similar to the placebo, with no new safety signals identified compared with the interim analysis. The rates of serious AEs were numerically higher in the placebo group with treatment discontinuation, all cause grade 3 and 4 AEs, and laboratory abnormalities similar across both groups. 

In the open letter, O’Day said Gilead has also increased supplies of the drug, with enough remdesivir on-hand in the United States to treat all hospitalized patients, even in the event of a future spike. He said they expect to meet global demand in October and signed an agreement with the European Commission that enabled 37 participating countries in the European Union and European Economic Area, as well as the United Kingdom, to purchase remdesivir for real-time demand and stockpiling needs.

Finally, he said ongoing studies are investigating intravenous treatment in the outpatient setting and an inhaled solution that could potentially be administered earlier in the course of the disease. Other studies are using remdesivir as the backbone in a combination treatment, offering new clinical data in the ongoing COVID-19 research.

“Our journey with remdesivir has entered a new phase, with the potential to make an even greater impact on the pandemic,” O’Day said. “We have rich new data to show how it might best be used to benefit patients and, with the increase in supply, many more patients can now access remdesivir worldwide. At the same time, we continue to explore its potential.”

REFERENCES
  1. Final Results of National Institute of Allergy and Infectious Diseases’ ACTT-1 Trial Published in New England Journal of Medicine Expand Clinical Benefits of Vaklury (remdesivir) for the Treatment of COVID-19 [news release]. Gilead; October 8, 2020. https://www.gilead.com/news-and-press/press-room/press-releases/2020/10/final-results-of-national-institute-of-allergy-and-infectious-diseases-actt-1-trial-published-in-new-england-journal-of-medicine-expand-clinical-bene. Accessed October 9, 2020.
  2. An Open Letter from Daniel O’Day, Chairman & CEO, Gilead Sciences [news release]. Gilead, October 8, 2020. https://stories.gilead.com/articles/an-open-letter-from-our-chairman-and-ceo-oct-8. Accessed October 9, 2020.