Efficacy of Oral Remdesivir Compared to GS-441524 for Treatment of Cats with Naturally Occurring Effusive Feline Infectious Peritonitis: A Blinded, Non-Inferiority Study

Abstract

Nucleoside analogs GS-441524 and remdesivir (GS-5734) are effective in treating cats with feline infectious peritonitis (FIP). However, no studies have compared the efficacy between antiviral medications. The objective of this study was to evaluate the efficacy of orally administered GS-442514 (12.5-15 mg/kg) compared to orally administered remdesivir (25-30 mg/kg) in a double-blinded non-inferiority trial. Eighteen cats with effusive FIP were prospectively enrolled and randomly assigned to receive either GS-442514 or remdesivir. Cats were treated daily for 12 weeks and evaluated at week 0, 12, and 16. Survival and disease remission at week 16 were compared between groups. Five of 9 (55%) cats treated GS-441524 and 7/9 (77%) cats treated with remdesivir survived, with no difference in survival rate (p = 0.2). Remdesivir fulfilled the criteria for non-inferiority with a difference in survival of 22% (90% CI; -13.5-57.5%). Three of the 18 cats died within 48 h of enrollment. Excluding these cats, 5/6 (83%) of the cats treated with GS-441524 and 7/9 (77%) of the cats treated with remdesivir survived. These findings suggest that both orally administered GS-441524 and remdesivir are safe and effective anti-viral medications for the treatment of effusive FIP. Further optimization of the first 48 h of treatment is needed.

Keywords: FIPV; antiviral; coronavirus; feline coronavirus; nucleoside analog; therapy.

Figure 1

Study timeline indicating timing of evaluation and study drug administration. Weight was recorded weekly for the study duration. (Figure made with Biorender).

Figure 2

Consort diagram describing study screening, exclusions, intention to treat animals that were allocated to the antiviral treatment group, and cats that were excluded from the final analysis. (Image made with Biorender).

Figure 3

Treatment difference. The difference in survival rate of remdesivir minus GS-441524 (black dot) displayed with the 95% confidence interval of the difference in survival. A solid vertical line is placed at 0% difference in survival and a dotted vertical line represents the 15% non-inferiority limit.

Figure 4

Survival curves: (a) survival curve that displays all-cause mortality; and (b) survival curve with cats that succumbed to disease within the first 48 h of therapy censored from analysis. Cats treated with GS-441524 are represented by the blue line and cats treated with remdesivir are represented by the red line.

Figure 5

(a) Lymph node exhibiting minimal positive IHC coronaviral antigen; (b) lymph node histopathology consistent with pyogranulomatous inflammation; and (c) liver histopathology exhibiting inflammation of the capsule (capsulitis).

Figure 6

Weight (kg) measured weekly for individual study cats. Truncated lines represent non-surviving cats. Cats in the GS-441524 treatment group are represented by blue lines and cats in the remdesivir treatment group are represented by red lines.

Figure 7

Clinicopathologic features throughout the study period including: (a) hematocrit; (b) neutrophil count; (c) lymphocyte count; (d) serum albumin concentration; (e) serum albumin:globulin ratio; and (f) serum globulin concentrations. Cats treated with GS-441524 are represented by blue circles and cats treated with remdesivir with red triangles. The median value represented with a horizonal black line.

Figure 8

Feline coronavirus antibody serology at study week 16, presented as a reciprocal endpoint titer. Specimens were not tested at dilutions higher than 1:20,480. Cats in the GS-441524 treatment group are in represented by blue dots, and cats in the remdesivir treatment group are represented by red triangles. The black horizontal line represents the median antibody titer.