FIP research: New hope for cats (and maybe humans)

By Emily Singler, VMD - 11/14/2022

Editor’s note: This is a new monthly column for NEWStat about One Health and the human-animal bond. Catch up on last month here.

As veterinary professionals in 2022, few of us would have imagined that we would be diagnosing a fatal disease in young cats and telling our clients we know of a treatment but that we can’t administer, sell, or prescribe it—then suggesting they visit a Facebook page to purchase unmarked vials of a drug from China for thousands of dollars. But that is precisely the scenario in which we find ourselves in the diagnosis and treatment of feline infectious peritonitis (FIP) in the United States.

How did we get to a point where our only option is to suggest that our clients meet up with strangers from the internet with no veterinary training in parking lots to buy an unapproved medication to inject into their dying cats?

A brief history on the seemingly miraculous, unapproved treatment for FIP

Gilead Sciences, a US-based global pharmaceutical company, had been studying various anti-viral drugs for years with the goal of finding a treatment for the deadly Ebola virus in humans. Among the drugs they created and patented were GS-441524 and GS-5734—neither of which proved to be successful in treating Ebola.

Meanwhile, Davis Niels Pedersen, DVM, PhD, a professor emeritus of medicine and epidemiology at the University of California Davis, was fervently studying and trying to find a cure for FIP. He reached out to a friend, who was chief medical officer of Gilead Sciences at the time, to inquire about antiviral drugs that might help.

He received about 25 different drugs from their library to try, and two of them showed very promising results: GS-5734, now known as remdesivir, and GS-441524, which is metabolized to remdesivir in the body.

The results were incredible. They saw unheard-of cure rates in both artificially infected and naturally infected cats (between 80% and 100%). It seemed like the problem had been solved. Unfortunately, Gilead Sciences reportedly refused to license GS-441524, the simpler of the two molecules, for use in cats, and they later pursued remdesivir as a treatment for severely ill COVID-19 patients.

The fear was that performing the studies to secure FDA approval for GS-441524 in cats might hamper efforts to approve GS-5734 (now remdesivir) in humans because if studies using GS-441524 to treat cats had any adverse effects or undesirable results, this could influence the analysis of remdesivir for human use.

Remdesivir is now conditionally approved for emergency use in humans to treat severe COVID-19 infections, but without full FDA approval, it can’t legally be used off-label by veterinarians. GS-441524 is not approved at all, so it cannot legally be used either.

As a result, desperate cat owners are left with no choice but to reach out to FIP Warriors, a global network made up of cat lovers, breeders, and rescuers—many of whom have been through treatment with their own cats. They help owners of sick cats get vials quickly, share notes on the best “brands” to purchase, and teach owners how to give daily subcutaneous injections to their cats.

These are all tasks that would normally be performed by veterinary professionals. The other missing part to the current scenario is the drug safety, efficacy, and oversight piece. There are reportedly significant variations in the safety and success rates of products from different manufacturers, with one version even being blamed for killing cats in January 2021.

Promising new research

Researchers at the University of California Davis, where Pederson first discovered the success of those two molecules in treating FIP in cats, are taking up the charge.

Krystle Reagan, PhD, DVM, Dip. ACVIM, assistant professor of medicine and epidemiology, is leading several studies to find a treatment that is “readily accessible to treat cats diagnosed with FIP.”

In collaboration with a team at the University of California San Diego, she is using CRISPR technology to develop a rapid test that detects viral genetic material. This study is still ongoing, but researchers hope it will yield a more definitive and rapid test that could replace the diagnosis by circumstantial evidence and exclusion that is currently the norm.

Reagan is also the principal investigator on a clinical trial evaluating the use of GS-441524 and remdesivir in oral formulations to treat FIP. She reports that the efficacy of the oral formulations of both drugs appears to be good, and that this can provide an alternative to the daily GS-441524 injections, which are known to be painful to cats.

Reagan’s colleague, Amir Kol, DVM, PhD, Dip ACVP (Clinical Pathology), associate professor of pathology, microbiology, and immunology, is leading a clinical trial of his own involving the use of mesenchymal stem cells (MSCs) along with GS-441524 in the treatment of FIP.

Regarding the mechanism of action of MSCs in the treatment of FIP, Kol stated, “We still do not know if MSC treatment is effective in FIP. … Nonetheless, based on previous data, we expected MSC treatment to benefit cats with FIP by promoting three critical pathways that: 1) Decrease inflammation; 2) Rejuvenate exhausted T cells; and 3) Regenerate lymphoid tissue post infection.”

This trial may add to our treatment arsenal for a rare, but serious, complication in human children as well. Kol draws parallels between FIP, with its “massive inflammatory response in conjunction … with an exhausted antiviral specific immune response” and MIS-C, multisystem inflammatory syndrome in children, which can be a severe complication of COVID-19 infection.

MIS-C, he notes, is characterized by “1) Coronavirus-induced systemic hyperinflammatory disease; 2) Young age; and 3) T cell exhaustion.” He hopes that FIP in cats will serve as a good model for MIS-C in children, and that the findings from this study will benefit the treatment of both species. If success is seen in cats, MSCs are easily sourced for clinical trials in humans in the future, marking an “immediate translatable impact on children’s health.”

Seeking FDA approval for cats and humans

While none of these studies guarantee that a drug will be approved for veterinary use, we can hope that, with the preponderance of evidence for the efficacy and safety of GS-441524 and remdesivir in cats, one or both drugs can become licensed and FDA-approved for use in cats.

Even full approval for use in humans would open doors to legal extra-label use in veterinary medicine. The more we learn about these disease models in cats and humans, the better we can refine the treatment and enhance the response rates in both species.

While this story started with treatment needs in animals taking a back seat to treatment needs in humans, the next chapter can include cats, cat owners, and veterinarians finally getting access to lifesaving options for FIP, and better treatments for severe disease in both species.

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FIP research: New hope for cats (and maybe humans)

A brief history on the seemingly miraculous, unapproved treatment for FIP

Promising new research

Seeking FDA approval for cats and humans

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