FOSTER CITY, Calif.–(BUSINESS WIRE)–Oct. 8, 2020– 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 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.
Please see below for important warnings and information about the authorized use of Veklury in the United States. In the United States, Veklury is an investigational drug that has not been approved by the FDA, and the safety and efficacy of Veklury for the treatment of COVID-19 have not been established.
About the ACTT-1 Trial
The Adaptive COVID-19 Treatment Trial (ACTT-1) is an international, randomized, placebo-controlled Phase 3 trial that evaluated a 10-day course of Veklury plus standard of care in more than 1,000 hospitalized adult patients with mild/moderate to severe symptoms of COVID-19, including those who were critically ill and required mechanical ventilation at screening. The trial was conducted by the National Institute of Allergy and Infectious Diseases, with input from and study drug donated by Gilead.
Veklury (remdesivir) is an investigational nucleotide analog invented by Gilead, building on more than a decade of the company’s antiviral research. Veklury has broad-spectrum antiviral activity both in vitro and in vivo in animal models against multiple emerging viral pathogens, including Ebola, SARS, Marburg, MERS and SARS-CoV-2, the virus that causes COVID-19.
Multiple ongoing international Phase 3 clinical trials are evaluating the safety and efficacy of Veklury for the treatment of COVID-19, in different patient populations, formulations, and in combination with other therapies. Based on available data from these studies, Veklury has been approved or authorized for temporary use as a COVID-19 treatment in approximately 50 countries worldwide.
As announced on October 1, 2020, Gilead is now meeting real-time demand for Veklury in the United States and anticipates meeting global demand for Veklury in October, even in the event of potential future surges of COVID-19.
Important Information about Veklury in the United States
In the United States, Veklury (remdesivir) is authorized for use under an Emergency Use Authorization (EUA) only for the treatment of hospitalized adult and pediatric patients with suspected or laboratory-confirmed COVID-19. Veklury must be administered via intravenous (IV) infusion and is supplied two ways: Veklury (remdesivir) for injection, 100 mg, lyophilized powder, or Veklury (remdesivir) injection, 100 mg/20 mL (5 mg/mL), concentrated solution.
Veklury is an investigational drug that has not been approved by the FDA for any use, and the safety and efficacy of Veklury for the treatment of COVID-19 have not been established. This authorization is temporary and may be revoked, and it does not take the place of the formal new drug application submission, review and approval process. For information about the authorized use of Veklury and mandatory requirements of the EUA in the U.S., please review the Fact Sheets and FDA Letter of Authorization available at www.gilead.com/remdesivir.
Serious and unexpected adverse events may occur that have not been previously reported with Veklury use. Hypersensitivity reactions, including infusion-related and anaphylactic reactions, have been observed during and following administration of Veklury. The use of Veklury is contraindicated in patients with known hypersensitivity to Veklury. Transaminase elevations have been observed in healthy volunteers and patients with COVID-19 in clinical trials who received Veklury. Patients should have appropriate clinical and laboratory monitoring to aid in early detection of any potential adverse events. Monitor renal and hepatic function prior to initiating and daily during therapy with Veklury; additionally monitor serum chemistries and hematology daily during therapy. Do not initiate Veklury in patients with ALT ≥5x ULN or with an eGFR <30 mL/min. The decision to continue or discontinue Veklury therapy after development of an adverse event should be made based on the clinical risk/benefit assessment for the individual patient.
Due to a risk of reduced antiviral activity, coadministration of Veklury and chloroquine phosphate or hydroxychloroquine sulfate is not recommended.
Healthcare providers and/or their designee are responsible for mandatory FDA MedWatch reporting of all medication errors and serious adverse events or deaths occurring during Veklury treatment and considered to be potentially attributable to Veklury. These events must be reported within 7 calendar days from the onset of the event. MedWatch adverse event reports can be submitted to FDA online at www.fda.gov/medwatch or by calling 1-800-FDA-1088.
About Gilead Sciences
Gilead Sciences, Inc. is a research-based biopharmaceutical company that discovers, develops and commercializes innovative medicines in areas of unmet medical need. The company strives to transform and simplify care for people with life-threatening illnesses around the world. Gilead has operations in more than 35 countries worldwide, with headquarters in Foster City, California.
For more information on Gilead’s response to the coronavirus outbreak please visit the company’s dedicated page: https://www.gilead.com/purpose/advancing-global-health/covid-19.
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors. Veklury is an investigational drug that has not been approved by the FDA for any use, and it is not yet known if Veklury is safe or effective for the treatment of COVID-19. There is the possibility of unfavorable results from ongoing and additional clinical trials involving Veklury and the possibility that Gilead and other parties may be unable to complete one or more of such trials in the currently anticipated timelines or at all. Further, it is possible that Gilead may make a strategic decision to discontinue development of Veklury or that FDA and other regulatory agencies may not approve Veklury, and any marketing approvals, if granted, may have significant limitations on its use. As a result, Veklury may never be successfully commercialized. In addition, there is also the risk that Gilead may be unable to effectively manage the global supply and distribution of Veklury. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2020, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.
Source: Gilead Sciences, Inc.
Posted: October 2020
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