The US Food and Drug Administration (FDA) has granted a label expansion for the antiviral remdesivir (Veklury; Gilead Sciences) to include treatment of COVID-19 in patients with mild, moderate, and severe hepatic impairment, without requiring dose adjustments, according to a news release from Gilead.
The expanded indication follows recent decisions in the US and Europe to extend the approved use of remdesivir for treatment of COVID-19 in individuals with severe renal impairment, including patients on dialysis, according to the statement. The approval of the Gilead sNDA makes remdesivir the “only approved antiviral COVID-19 treatment that can be used across all stages of liver disease,” the company stated.
“With the recent increase in levels of COVID-19 circulating in the US, the risk to vulnerable individuals persists, including for those with hepatic impairment,” Frank Duff, MD, senior vice president and head of the virology therapeutic area at Gilead Sciences, said in the statement. “This approval demonstrates Gilead’s ongoing commitment to COVID-19, including our focus on vulnerable populations.”
According to the company, remdesivir (100 mg injection) is indicated for the treatment of COVID-19 in adults and pediatric patients in the US, who are either hospitalized or who are not hospitalized, but have exhibited mild-to-moderate COVID-19 and are at high risk for progression to severe COVID-19.
The pharmacokinetics (PK) of remdesivir had not yet been evaluated in patients with hepatic impairment, said Gilead, prompting evaluation of the antiviral’s safety and PK profile in the phase 1, multicenter, open-label, single-dose GS-US-540-9014 study. Study participants had either normal hepatic function or moderate or severe hepatic impairment.
The study found “no new safety signals,” according to Gilead. Based on the findings, the FDA has revised the official prescribing information for remdesivir, indicating that no adjustments to dose are needed “across all stages of liver disease.”
Hepatic laboratory testing is still recommended, however, for all patients before treatment is started and throughout treatment as deemed clinically necessary.
Labeling also continues to recommend that discontinuation of remdesivir should be considered for patients whose alanine transaminase (ALT) levels rise to “10 times the upper limit of normal” or if symptoms of hepatic inflammation are seen concomitantly with an elevation in the liver function test results.
Noting that persons with hepatic disease are at risk for complications associated with COVID-19 infection, Douglas Dieterich, MD, director at the Institute for Liver Medicine in the Icahn School of Medicine at Mount Sinai, said “The update to the safety profile and dosing recommendations for Veklury for those living with liver disease is important to this vulnerable population…While COVID-19 is no longer a public health emergency, the virus continues to present a threat to those with underlying conditions.”
According to the statement, more than 100 million people in the US live with hepatic disease and treatment options for COVID-19 are limited.