Research redux: Renewed hope for FIP

The surge in exotic diseases such as Ebola and SARS in people is proving to be a boon for cats.

Both diseases have prompted intensive research into drugs that will cure or inhibit them. One of the most promising is Remdesiver (GS-5734), which, in studies, has proven effective in preventing Ebola in rhesus monkeys and inhibiting coronaviruses in infection models of mice.

These findings inspired longtime feline infectious peritonitis (FIP) researcher Niels Pederson, DVM, PhD, to get the old gang back together for one last job.

Pederson, professor emeritus of medicine and epidemiology at the University of California, Davis (UC Davis), led a groundbreaking 2016 study that showed the antiviral drug GC376 could be effective in treating FIP—the first real hope that FIP, usually considered a fatal diagnosis, could be cured through drug therapy. Not content with that triumph, he and colleagues from UC Davis and Kansas State University decided to launch their own study of GS-5734, which included a field trial in cats with naturally occurring FIP.

Those results, published this month in the Journal of Feline Medicine and Surgery, showed that a less-chemically complex variant of GS-5734 (called GS-441524) was highly effective in treating FIP.

FIP is one of a number of chronic viral infections of cats that resemble those in people—others include feline leukemia and feline herpesvirus. The researchers write: “The infectious agent [in FIP] is a mutant coronavirus (FIPV) that is notoriously difficult to control: the parent enteric coronavirus is present in virtually all catteries and shelters and is shed by 60% or more of pet cats from multicat households, and vaccines are ineffective.”

The researchers enrolled 31 cats in the study; 26 completed it.

Clinical response in those 26 cats to GS-442524 was dramatic: fever usually resolved within 12 to 36 hours, along with a marked improvement in appetite, activity levels, and weight gain. More impressively, cats with noneffusive (dry) FIP and older cats responded just as well to the drug treatments as younger cats and cats with effusive (wet) FIP.

Currently, 24 of the 26 cats remain healthy, with 1 having succumbed to FIP disease and 1 to unrelated heart disease. Eighteen of these cats underwent just one round of treatment; the remaining eight suffered disease relapses, but these were successfully treated with a second round of treatment. Two of the cats required a third treatment.

NEWStat contacted Pedersen to find out more about this revolutionary research.

NEWStat: How does your new study on treating FIP with GS-441524 tie in with your 2016 study on GC376? How does the efficacy of the two drugs compare?

Niels Pederson: The present research studies on GS-441524 are exact parallels of our earlier studies with GC376. The major differences were that GC376 was a protease inhibitor while GS-441524 was a nucleoside analog (RNA chain terminator).GC376 was discovered by veterinary researchers at Kansas State University interested in animal disease, while GS-441524 was discovered by scientists at Gilead Sciences interested in human diseases. We were blessed by great collaborations with both groups. Both drug studies started with basic research into the behavior of each drug in tissue culture and in laboratory cats. These studies provided the necessary knowledge to take them into field trials where they were tested against owned cats with naturally occurring FIP. The efficacy of both drugs in laboratory cats and in owned cats was similar, although our studies with GS-441524 had the benefits of all the knowledge on dosage regimens that we discovered with GC376.

NEWStatIt sounds as if the field of FIP treatment is cracking wide open.

NP: Yes, these were both major discoveries because they were one of the first times we were able to apply what has been learned from RNA virus diseases (e.g., HIV/AIDS, Hepatitis C, Ebola, MERS, SARS) of humans to an RNA virus disease (e.g. FIP) of cats.

NEWStat: What’s changed since the days when a diagnosis of FIP was essentially a death sentence for cats?

NP: The [idea] of using small molecules to inhibit specific proteins involved in RNA virus replication. Although you can’t always use the exact same type of drugs for both humans and cats, [the concepts behind developing those drugs] are the same.

NEWStat: Do you see a time when FIP will be a non-dire condition that’s easily manageable through drug therapy?

NP: We feel that antiviral drugs like GS-441524 and GC376—either used alone or in combination—will become the bulwark of curing cats of FIP within the next decade. . . . It is also our hope that these studies will open the door for the application of modern antiviral drug therapy for a number of other serious viral infections of our animal companions.

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