Remdesivir receives FDA approval for COVID-19
The US Food and Drug Administration (FDA) has given full approval to the first drug to treat COVID-19. The antiviral Veklury (remdesivir, Gilead Sciences) received approval on 22 October to treat older children and adults who are hospitalized with COVID-19.Veklury had previously received an emergency use authorization EUA on 1 May 2020 for a broader population that also included hospitalized pediatric patients weighing 3.5 kg or more.
"The FDA is committed to expediting the development and availability of COVID-19 treatments during this unprecedented public health emergency," said FDA Commissioner Stephen M. Hahn, MD, in a press release announcing the approval. "Today's approval is supported by data from multiple clinical trials that the agency has rigorously assessed and represents an important scientific milestone in the COVID-19 pandemic.
Gilead’s Veklury application was given fast track and priority review designations, as well as a Material Threat Medical Countermeasure Policy Review Voucher.
Three randomized controlled trials formed the basis for Veklury’s approval, said the agency, which released a summary of its review of the data. A double-blind, placebo-controlled trial led by the National Institute of Allergy and Infectious Diseases enrolled 1,062 hospitalized patients and randomized them 1:1 to receive Veklury or placebo in addition to standard of care. In this trial, dubbed ACTT-1, disease severity ranged from mild to severe in the study population. Patients recovered – that is, were either discharged or did not require oxygen if still hospitalized – at a median 10 days if they received Veklury, compared with 15 days if they received placebo. Improvement at day 15 was also statistically more likely for the Veklury group.
The second trial was randomized and multi-center, but open-label. It enrolled hospitalized adults with moderate COVID-19 disease. Nearly 600 patients were randomized 1:1:1 to receive Veklury for either 5 or 10 days, or placebo. In this trial, patients who received 5 days of Veklury had a significantly better chance of improving by study day 11 compared with the standard of care group; those who received Veklury for 10 days did numerically better, though the difference was not statistically significant.
Another open-label randomized multi-center trial enrolled 397 patients and randomized them 1:1 to receive 5 or 10 days of Veklury, assessing their clinical status on study day 14. In this study, treatment duration did not make a significant difference in clinical improvement, recovery or mortality.
“As part of the FDA's Coronavirus Treatment Acceleration Program, the agency will continue to help move new medical products to patients as soon as possible, while at the same time determining whether they are effective and if their benefits outweigh their risks," said Hahn. The FDA’s announcement also details Veklury’s potential side effects, which include elevated liver enzymes and liver injury, as well as allergic reactions.
More information is still needed about the risk of these serious adverse events as well as safety in pediatric and other vulnerable populations, noted FDA in its summary review of Veklury data. ”These limitations result, in part, from the important public health priority of expediting the review of a safe and effective therapeutic in the setting of an unmet medical need and will be addressed post-approval,” noted the officials.
“Post marketing requirements (PMRs) will be issued for the conduct of clinical trials in pediatric patients and in patients with renal or hepatic impairment. PMRs will also be issued for the conduct of a [drug-drug interaction] trial with rifampin and a dedicated QT trial,” to assess the risk of arrhythmias caused by prolongation of the electrocardiographic QT interval, according to the FDA summary. Postmarketing commitments will also be issued to accrue pharmacokinetic data in pregnant patients.
FDA