Efficacy and safety of the nucleoside analog GS-441524 for treatment of cats with naturally occurring feline infectious peritonitis

Pedersen, Niels C; Perron, Michel; Bannasch, Michael; Montgomery, Elizabeth; Murakami, Eisuke; Liepnieks, Molly; Liu, Hongwei

GS-441524 is the second targeted antiviral drug after GC376 to be evaluated for the treatment of cats with FIP in the past two to three years. 6, 12, 15 These two drugs inhibited viral replication in two very different manners, either by terminating viral RNA transcription or blocking viral polyprotein cleavage. Both processes are well-established targets for several viral diseases in people. 1 A key question is how treatment with a nucleoside analog compares with that of a viral protease inhibitor. The two drugs gave virtually identical results in tissue culture and experimental cat infection studies. 12, 15 However, efficacy against naturally occurring FIP appeared greater with GS-441524 than GC376. Six of 20 cats treated with GC376 remain in remission to date (Pedersen NC, unpublished data, 2018) compared with 25/31 cats treated with GS-441524. Disease relapses that did not respond to retreatment occurred in 14/20 cats with GC376 and only one cat treated with GS-441524. 6 Eight of the 14 relapses associated with GC376 were neurological in nature, 6 compared with 2/8 relapses with GS-441524. One of two neurological relapses in GS-441524-treated cats responded to retreatment at a higher dosage, whereas neurological relapses with GC376, even with increased dosage, were no longer treatable. 6 Both treatments caused similar injection site reactions. Both drugs appear to be quite safe, although GC376 interfered with the development of permanent teeth when given to younger kittens. 6 Although the results of field testing appear to favor GS-441524, some of the difference may have been influenced by how the two drugs were administered. Efficacy of GC376 may have improved if all 20 cats had been treated without interruption for 12 weeks, rather than treated for progressively longer periods starting at just 2 weeks. 6 Five of the six cats cured with GC376 were among the seven cats that were treated continuously for 12 weeks, while only one of 13 cats treated one or more times for shorter periods of time was cured. These shorter treatment times were essential for determining the 12 week period used for all cats in the present study. The GC376 field trial also involved fewer cats and was constrained by a limited supply of the drug, which made it difficult to test other dosage regimens. Therefore, GC376 should be further studied using a minimum of 12 weeks with a higher dosage and a larger number of cats before making any final comparisons. It would also be important at some time in the future to evaluate both types of drugs in combination, as done for HIV/AIDS and hepatitis C.