Guest post by Ingrid R Niesman, MS PhD
Despite the intrusion from COVID-19, or perhaps because of the pandemic, more and more Feline Infectious Peritonitis (FIP) infected cats are surviving and thriving in 2022. Just a few short years ago, all FIP positive cats died.
I attended the inaugural FIP symposium in November, 2019 sponsored by the Winn Feline Foundation, now EveryCAT Health Foundation. Honestly, at the time, I had no idea of the extent of this disease, the desperation of cat parents and the lack of money for research. But more importantly, I came away understanding the real tangible hope that owners, veterinarians and scientists experienced for the first time in over 60 years.
What is FIP?
FIP is still a mysterious coronavirus disease. Easily transmitted between cats, equally as easily cleared by most, but sadly in a small subset of cats, the virus changes from a non-pathogenic form to one that aggressively infects intestinal macrophages. As moderators of the innate immunity branch, macrophages kickstart a cyclic inflammatory storm we now understand as FIP.
FIP exists in several variant forms, making a definitive diagnosis problematic. However, markers, such as serum amyloid A (SAA) elevation are being investigated as possible diagnostic keys for early detection. Currently, tedious microscopic examinations of tissue effusions remains the most accurate tests for a full diagnosis. As I have learned, early diagnosis and treatment can be the difference between life and death for stricken cats.
History of FIP therapies and prevention
Coronaviruses are among the most complex and difficult to treat viruses. Acquired immunity can wane quickly and antivirals are proving difficult to discover and easily overcome by viral resistance. Historically, coronavirus vaccines for common animal diseases have short durations of protection and due to genetic variants must be administered frequently and in mass procedures to control disease.
The first real breakthroughs in finding effective antiviral drugs for FIP came in 2016. Dr. Niels Pederson published the first of several studies demonstrating effective treatment, and remarkably, probable cures, for two drugs, Gilead Sciences’s GS-441524 and a Kansas State developed drug now acquired by Anivive Lifesciences, Inc. GC-376. Many of the original cats that survived those trials are still living today.
Anivive Lifesciences, Inc. is well on their way towards FDA approval for GC-376. Gilead Sciences is an entirely different story. Whether it was just greed or a belief that treating human and concurrently cats with essentially the same drug would complicate human US FDA approval or accelerate viral resistance, they have chosen to pull animal use of GS-441524 for FIP within the US. The irony is that remdesivir, the human version, did win restricted FDA approval for COVID-19 and is available worldwide for treating high risk and hospitalized patients, even though the efficacy of this treatment is under evaluation. Yet, Gilead remains steadfast in their resistance to saving cat lives.
With the US FDA approval for animal use of GS-441524 is highly unlikely in the US, other countries have taken a different route. Remdesivir is approved for veterinary use and clinics can legally prescribe the drug for FIP in the United Kingdom and Australia. As Gilead licensed foreign manufacturers, but not US ones, the rest of the world has access to remdesivir for FIP. Since 2020, clinicians in Australia have treated cats with cat-specific remdesivir formulations for IV or subcutaneous injections. Recently the UK compounding manufacturer BOVA has begun distribution within the UK as well.
What are some new avenues of investigation for novel therapies?
Paxlovid, marketed by Pfizer and conditionally approved for human use by the FDA, is a combination of a modified version of GC-373 (the prodrug for GC-376) and an HIV antiviral. This combo has shown some promise in the treatment for FIP. Unfortunately, there are circulating reports that in humans, COVID-19 relapses are occurring with committal increases in disease severity following Paxlovid treatment.
Merck & Co. has entered the field by modifying an old drug to increase oral absorption. EIDD-2801, also known as molnupiravir, has demonstrated efficacy in FIPV cell-based experiments. The FDA has given emergency use human approval but not animal approval. In an unpublished global trial, there was a 100% survival of FIP cats, some within 6 weeks of treatment. Given this information, the availability of oral administration and the potential for use in GS-441524 resistant cats, there is already a crowdsourcing market for this drug developing. Perhaps Merck will do the compassionate thing and seek animal approval as quicky as possible, allowing cats immediate access to this potentially lifesaving therapy.
Overcoming panic – start treatment today
Despite the legal implications and fear of using untested vials of liquid or generic white pills, cat parents worldwide are placing trust in themselves rather than our medical and veterinary community. In an unprecedented fashion, fired up individuals have worked under the radar to provide GS-441524 for panicked clients, usually within 24 hours or less. Medical chemists are working unregulated to synthesize quality drugs for an increasing demand. Untrained people are learning to calculate dosages, how to inject cats with a painful drug daily and treat and comfort their sick cats.
All of this is not cheap. People are paying on average around $5000 to save their pets. The question we should all be asking is why a company would not cater to this obviously lucrative market?
To better understand this unique situation, researchers have studied how effective unlicensed drugs and untrained people are for FIP cat survival. Published in 2021, this survey based study reveals that an ad hoc system can work (Jones, Novicoff, Nadeau, Evans 2021). From a pool of 393 respondents, a remarkable 96.7% of the treated cats were alive.
“Everyone wants to know if unlicensed drugs are effective, but the compelling part of this survey is how non-vet professionals are figuring out how to inject their cats for 84 days successfully and still be effective,” explains author Wendy Novicoff, Ph.D. “Since we used social media to find our respondents, there probably was some enthusiasm bias. However, in prospective studies we are currently conducting, we are still seeing an 85-90% cure rate. You can’t beat that.”
Random citizens taking control has shaken the veterinary world
The full story of this underground movement sounds like a work of fiction. Indeed, when reason and rationality prevails over poor business decisions, we all win or in this case, our cats do. Desperate people found a way to save cats lives outside of mainstream medicine and are doing so without supervision. Only 9% of the survey parents received any significant veterinary help.
Clinicians are wary of any involvement with an illegal drug. According to the information presented during the symposium, performing the diagnostic follow through testing and supportive care during treatment is not a violation. Helping during treatment will allow for more serious data collection and analysis in the future. Too many clinicians have no idea what is happening.
“Without random citizens stepping up to fill a void, there would be no FIP Warriors or other support groups,” according to Dr. Novicoff. “nearly 50,000 cats worldwide would be dead today.”
As I’ve written about previously, the loss of a cat to FIP remains an open wound, frequently for decades. For Dr. Novicoff, her grief turned to action, “not to start a movement, but to amplify it.”
Why FIP research matters, now and in the future
If we as humans have learned anything from the past two and half years, it should be that microbes can defeat us all. Viruses easily mutate. Bacteria can live in expanding ecological niches. There are unknown or undisturbed reservoirs of potential pathogens spread worldwide. All life is interconnected and helping one species helps us all.
Research and drug discovery for antivirals was a much lower priority for human medicine for decades. Interest waxed and waned as each new scary virus surfaced; SARS, MERS, Ebola. Little attention was paid towards viral infections in our companion animals. Nevertheless, without the groundbreaking work of devoted feline virus scientists, our understanding of human coronaviruses would still be in the dark ages. Companies like Gilead Sciences owe feline medicine researchers for their dedication and preliminary work. There is no way that we could have moved so quickly on COVID-19 vaccination or treatment without the work of animal virologists.
Ingrid R. Niesman MS PhD is the Director of the SDSU Electron Microscope Imaging Facility at San Diego State University. She graduated from Utah State University and received her MS from the University of Illinois-Urbana-Champaign. After 30 years of technical electron microscopy, cell biology, neuroscience and infectious disease research, Dr. Niesman completed her PhD in the UK at the University of Sunderland. Her work experience includes time at LSU Medical School, Washington University, UAMS in Little Rock, UCSD, TSRI and a postdoctoral year at CALIBR in La Jolla, CA. She has worked for at least two National Academy of Science members and is credited with over 50 publications. She can be reached at firstname.lastname@example.org