COVID-19: Remdesivir wins US FDA nod for severe renal impairment

Remdesivir can be used in COVID-19 patients with severe renal impairment, including those on dialysis, according to recent US FDA approval of its expanded indication based on results of the REDPINE trial.

“Renal disease is a major risk factor for COVID-19 mortality,” said Dr Jose Santos of Hospital Universitari Germans Trias i Pujol, Badalona, Spain, at the 33^rd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2023). “However, no antiviral treatments were available for hospitalized COVID-19 patients with severely reduced renal function.”

REDPINE, a phase III, randomized, double-blind, placebo-controlled, multicentre trial, evaluated the efficacy, safety, and pharmacokinetics of remdesivir in hospitalized COVID-19 patients with estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m² (n=243; mean age, 69 years; male, 57 percent). Patients were randomized 2:1 to receive intravenous remdesivir (200 mg on day 1, followed by 100 mg QD on days 2–5) or matching placebo, in addition to standard of care. [Santos JR, et al, ECCMID 2023, poster 2635; Veklury US Prescribing Information]

The trial included patients with end-stage renal disease (ESRD; eGFR <15 mL/min/1.73 m²; 37 percent) requiring dialysis, acute kidney injury (AKI; 37 percent), and chronic kidney disease (CKD; eGFR <30 mL/min/1.73 m²; 26 percent). Most patients (58 percent) were on low-flow oxygen, 22 percent were on room air, and 19 percent were on high-flow oxygen. None were on invasive mechanical ventilation.

“REDPINE was underpowered to assess efficacy because of lower-than-expected enrolment, which was due to loss of clinical equipoise with patients often receiving remdesivir outside of the trial’s scope,” reported Santos.

“Remdesivir was generally safe and well tolerated [in patients with severe renal impairment],” pointed out Santos. The most common treatment-emergent adverse events (TEAEs) by preferred terms were hypotension (11 percent vs 5 percent for remdesivir vs placebo), respiratory failure (6 percent vs 13 percent), and constipation (7 percent vs 9 percent). TEAEs related to the study drug (any grades) were reported in 13 patients (8 percent) in the remdesivir group and 3 patients (4 percent) in the placebo group, while no patients experienced serious TEAEs related to the study drug. Similar proportions of patients in each group developed stage 2 or 3 AKI, required renal replacement therapy or died by day 29, irrespective of baseline AKI (33 percent vs 40 percent for remdesivir vs placebo; p=0.32) or CKD (34 percent vs 30 percent; p=0.81) status.

“No new safety signals were identified with increasing plasma exposures to remdesivir’s predominant metabolite [GS-441524] and excipient [sulfobutylether-β-cyclodextrin sodium (SBECD)],” highlighted Santos. “No dose adjustment is recommended for patients with eGFR <30 mL/min/1.73 m², regardless of the need for dialysis.”

Results of REDPINE, together with those of a phase I pharmacokinetic study (GS-US-540-9015), led to the US FDA’s approval in July 2023 of remdesivir’s expanded indication for COVID-19 treatment in patients with severe renal impairment, including those requiring dialysis. This makes remdesivir the first and only COVID-19 antiviral approved for use across all stages of renal disease. According to its updated prescribing information, dose adjustment is not required for patients with renal impairment, and eGFR testing is no longer required before or during treatment with remdesivir. [www.gilead.com/news-and-press/press-room/press-releases/2023/7/fda-approves-veklury-remdesivir-for-covid19-treatment-in-patients-with-severe-renal-impairment-including-those-on-dialysis; Veklury US Prescribing Information; Nirmatrelvir/Ritonavir Prescribing Information; Molnupiravir Prescribing Information]