- Media Repost
Legal treatment for FIP still years away - P2
Biotech companies, pet owners, veterinarians plot different courses
August 22, 2019 By Lisa Wogan
Susan Gingrich adopted a lynx blue point Birman named Bria in 2004. The kitten looked like a long-haired Siamese but sometimes acted like a dog. She retrieved balls and begged at the dinner table. But at five-months-old, Bria's playful energy crashed. A series of visits to the veterinarian led to a diagnosis of feline infectious peritonitis, or FIP. Gingrich had never heard of the incurable and nearly always fatal disease.
The veterinarian put Bria on prednisone and drained fluid that had accumulated around her lungs, a sign of what is known as the "wet" form of FIP, to make her temporarily comfortable. (See sidebar for more about FIP.) Bria died before her first birthday.
"She was such a little fighter," Gingrich said. "She changed our lives." At a burial service for Bria, Gingrich promised to do something about FIP in the kitten's memory.
Every day, Gingrich said, she thinks, "What can I do to end FIP today?" Fifteen years after Bria's death, "It's still my main goal in life," she said.
A political activist in Tennessee, Gingrich founded the Bria Fund in 2005, with a donation from her brother, Newt Gingrich, former speaker of the U.S. House of Representatives. Working through the Winn Feline Foundation, a 50-year-old not-for-profit dedicated to improving feline health through research and education, the Bria Fund began in 2008 to support research into FIP. That research includes efforts to prevent transmission and to develop a diagnostic blood test, vaccine and treatments, including GS-441524 and GC376. These antiviral therapies interrupt the virus's ability to replicate, and in clinical trials have reversed FIP in some cats.
While both drugs remain experimental and have not been approved by the U.S. Food and Drug Administration, the success of the clinical trials has fueled the production in China of copycat drugs. In the past year, owners of FIP-affected cats around the world have connected with Chinese suppliers to purchase the drugs and treat their cats, with or without the assistance of a veterinarian.
This gap between an effective illegal treatment and a legal one reveals some of the challenges hampering the development of veterinary drugs. It also creates some specific ethical and legal challenges for veterinarians trying to come up with the best way to treat cats with the deadly condition.
‘A very big rift'
Gingrich was an early and active member of a Facebook group called FIP Fighters, established in 2009, which provides support and information on FIP diagnosis, care, research and more. As a group administrator, she had advocated for banning discussions of unlicensed and unapproved treatments such as GS from China. (Gingrich has since left FIP Fighters.)
She is frustrated by the black market. "It's given us stress and problems and headaches for about a year now," she said.
She said she is aware that unapproved GS and GC have been effective for some cats, but she's heard that there have been adverse reactions to the drugs.
Her concerns cover a gamut, from the fact that the drugs are not FDA-approved and proven safe to the idea that some owners forgo proper diagnosis and veterinary involvement, instead learning how to give injections from social media sites. "People are being told, ‘Don't spend your money on diagnostic tests, just buy GS, give it to your cat and if your cat gets better it means it was FIP,' " she said. Following that process, pet owners might miss a different condition that needs treatment or waste their money and inject their cats unnecessarily, she explained.
Furthermore, the drugs are expensive — reportedly running earlier this year between $10,000 and $30,000 for a full course of treatment. Gingrich frets that desperate cat owners will get into financial binds. Although competition is driving prices down, posts by members of FIP Warriors, another Facebook group, suggest that owners do struggle over the cost of treatment.
Some members say that saving a cat, or at least trying, is worth the financial pain. Others lament that they can't afford it. Some try to raise money via GoFundMe campaigns or borrow money, including, in at least one case, an owner who posted that she planned to use money from a student loan.
The Winn Feline Foundation, too, does not support the pay-or-die choice unapproved drugs currently pose. "Our goal is that that is a decision that people never have to make," said Steve Dale, a long-time board member with the Winn Feline Foundation. He calls the high prices unacceptable and unethical. "Never mind that we don't know it's going to work and that it's unregulated."
In the short term, however, owners of cats with FIP have to make choices now. Peter Cohen, a cat lover in Southern California who raises money for FIP research at his site ZenByCat, said he refers people who want to try the drugs to the FIP Warriors Facebook group. Cohen knows firsthand the power of these antivirals. His own cat, Smokey, was part of a 2016 clinical trial at the University of California, Davis, School of Veterinary Medicine. Smokey entered the trial with FIP. He exited as a healthy cat. Nearly three years later, Smokey is still going strong.
Cohen believes withholding information about the Chinese medications is unethical.
"There is still a very big rift between those who believe only regulated drugs should be used and those who feel saving FIP cats is more important than caring about legalities," he said. "My own belief is that until there is a legal path to buy these drugs, it makes sense for people to buy them online from these sources."
Further, Cohen said, the situation is changing rapidly as more and more people avail themselves of unapproved GS. He reports, for example, that the price for a full, 12-week course of GS has dropped over the past four months to between $1,000 and $5,000, depending on the weight of the cat and the type of FIP. He concedes that the price is still out of range for many people.
Cohen does worry that the talk on social media about recovered cats will lead the public to think FIP has been cured and stop funding studies. "These two drugs are just the first of what was meant to be a steady progression of better, cheaper, faster, easier-to-use drugs," he said. "The message I want to get out from ZenByCat is that we support the use of these drugs and hope people will continue to fund research for better drugs, better FIP tests, and ultimately, for a vaccine."
Fate of legal drugs in the U.S.
Legal and less expensive GS and GC could go a long way toward quenching the black market. This step is currently in the hands of two California-based companies: Gilead Sciences and Anivive Lifesciences.
Gilead, a publicly traded biomedical company that makes drugs for HIV and hepatitis C, owns the patent for GS-441524, which was more effective than GC in treating FIP in clinical trials. GS-441524 is related to a drug Gilead has developed to treat Ebola called GS-5734, or remdesivir.
A Gilead spokesperson told the VIN News Service that it is holding off on licensing GS-441524 to other parties for commercial development until remdesivir has FDA approval.
This inaction angers Gingrich, who is a Gilead shareholder. "Every single day nothing happens, cats are dying all over the world because of FIP," she said. In June, she sent a letter to Gilead chairman and CEO Daniel O'Day (with copies to her elected representatives and President Donald Trump) asking that the company do more to facilitate bringing GS to market.
"With successful GS-441524 clinical trials, all the cat world thought this amazing cure would be on its way to the market," she wrote. "After all the work and collaboration, it was devastating to learn that UC Davis licensing of this game changing drug for use in cats would not be permitted by Gilead."
Gingrich is referring to research by Dr. Niels Pedersen, whose clinical trials at UC Davis, School of Veterinary Medicine, identified GS as a safe and effective treatment for FIP.
"Your company is being spoken about in a derogatory manner widely in the cat community right now," Gingrich continued in her letter. "As a stockholder, I don't like it, but do understand their feelings. They can't comprehend why Gilead will not help their cats and more cats from dying from FIP when it's within its power."
Pedersen, too, expressed disappointment with Gilead's process.
"We have learned the hard way that these human drug companies have no great interest in veterinary products and veterinary-based research," he wrote in email responses to questions from VIN News. "Even when we successfully proved that one of their drugs could cure FIP, we ultimately failed to convince them that they should allow animal rights on the discovery and to help directly or indirectly with getting FDA approval and ultimate licensing."
A spokesperson for Gilead provided the following statement to VIN News:
"Gilead in the past has worked to make compounds with the potential to help animals available to developers with the expertise to advance medicines for veterinary use. This is why we shared GS-441524 with UC Davis to research its impact on feline infectious peritonitis (FIP).
"After we shared this compound with UC Davis, GS-441524 became an intermediate in the synthesis of remdesivir (GS-5734), which is under development for Ebola and other filoviruses. In addition, GS-441524 has been identified as a systemic metabolite of remdesivir in humans.
"At this time, we are not providing GS-441524 to other parties until remdesivir has FDA approval. This is to avoid any interference with the regulatory process, which could risk the approval of remdesivir by the FDA to treat human patients with Ebola or other filoviruses.
"We are, however, exploring options that would allow us to share GS-441524 before the FDA review is complete."
More immediate hopes are being pinned to GC376, which was developed by Drs. Kyeong-Ok Chang and Yunjeong Kim, virologists at Kansas State University College of Veterinary Medicine, and William Groutas, a medicinal chemist at Wichita State University, in collaboration with Pedersen.
The research process for GC is similar to Gilead's, according to Kim, in that the compound was developed to counter viral infections in humans, specifically MERS-coronavirus and human norovirus infections. In the Kansas State case, however, the same researchers tested them against animal viruses and found GC376 is a very strong inhibitor of the FIP virus.
Kansas State owns the patent and has licensed development of the compound to Anivive Lifesciences, a privately held biotech company.
Anivive's Chief Commercial Officer Chad Dodd said the company launched in 2015 to address the dearth of veterinary-specific medicines. He said only 15% of the diseases seen by companion animal veterinarians have approved veterinary-specific drugs. Veterinarians treat many conditions with drugs labeled for human use.
Early Anivive initiatives involve developing a vaccine for coccidioidomycosis, or Valley Fever, and a partnership with Karyopharm to launch an oral canine lymphoma treatment.
Dodd confirmed that the company is planning to shepherd GC376 through approvals and commercialization. He did not give a timeline. However, he did provide a link to a trial for FIP, which is identified as "coming soon" on the Anivive website.
"I'm thrilled Anivive is doing this," Dale of the Winn Feline Foundation said. "Some of the larger drug companies are concerned that there wouldn't be enough profit because there aren't enough cats out there. Anivive did the right thing. They just want to save kittens."
Pedersen thinks the experience with FIP drugs will have a major impact on drug research going forward. "It will definitely affect how companies focused on human health should react to situations arising from their research that might have as great, or perhaps greater, impact on animal health," he said.
"Animals, including cats, are often used to research human diseases, but here is an example where studies on human diseases have an immediate and highly sensitive impact on the health of one of our most important companion animal species," Pedersen said. "Interestingly, the fate of GC376 is assured because it was a product of veterinary researchers, while the fate of GS-441524 has been severely hampered by its origins in human research. If there was truly such a thing as ‘one health medicine' or ‘one health,' GS-441524 would have been treated the same as GC376."
One health is a global initiative to unite human and veterinary medicine to tackle interconnected problems of human, animal and environmental health.
How does the veterinarian fit in?
The situation creates ethical and legal challenges for veterinarians treating cats with FIP. In most states, veterinarians could get into trouble for purchasing and dispensing unapproved drugs.
"In all licensure laws, the licensee must follow the current standards of care. If a licensee were to recommend or utilize an unapproved drug, that would be a violation of the standard of care," said James Penrod, executive director of the American Association of Veterinary State Boards. "The Veterinary Medical Boards for each state would get involved if a complaint was made regarding a licensee recommending or using an unapproved drug, an investigation would take place, and possible disciplinary action would be determined on a case-by-case basis depending on the outcome of the actions."
Pedersen predicted that veterinarians nevertheless will feel compelled to act. "I suspect that owner pressures and the realities of the situation will drive more and more veterinarians into the black market, either directly or indirectly through owners who present them with both a sick cat and the drugs to treat it," Pedersen said.
Pet owners using GS and GC describe a range of veterinarian involvement with their cats' treatments. Some provide supportive care and diagnostics for pets being treated at home. Some teach pet owners to give injections of the medications. Some veterinarians or veterinary technicians inject the drugs at the clinic, usually after the owner signs a waiver absolving the practice of responsibility for adverse reactions to the medications. VIN News is unaware of any cases of veterinarians purchasing GS or GC themselves.
Dr. Hilary Quinn first learned about the antivirals well before it hit the black market. The Santa Barbara veterinarian provided care to Smokey, who has been in remission ever since participating in Pedersen's FIP clinical trial in 2016. "Prior to Smokey, my understanding of FIP was that it is a death sentence," Quinn said.
Now aware of black-market GS and GC, Quinn said that the next time she has an FIP case, she will discuss the drug status with affected owners. "I believe that it is important that owners receive information from their veterinarian instead of the internet," she said. (While Quinn wants to be the reliable source of information for her clients, some cat owners say it was their veterinarians who referred them to FIP Facebook groups in the first place.)
"I imagine I would have a very frank conversation with the owner about the unknowns of these black market GS and GC treatments," Quinn explained in an email to VIN News Service. "I would warn them of the risks and the potential adverse effects; and I would be certain to include detailed documentation of the conversation in my records. That being said, I would gladly counsel owners on how to administer injections at home. In addition, I would provide follow up physical exams, lab work, and management of any adverse effects."
She would draw the line at ordering the medications herself.
In Glasgow, Scotland, Dr. Diane Addie has thrown herself full-time into FIP treatment and research.
A veterinary virologist, Addie created a website called catvirus.com in 2000. At the time, she worked at the Veterinary Diagnostic Laboratory at the University of Glasgow Veterinary School and answered queries from veterinary surgeons. "I noticed a LOT of queries about FIP and thought — naively, as it turned out – that if I made the information available on a website, I could just be lazy and point people to the website," she wrote in an email to VIN News. "Turned out that I got MORE queries after starting the website!"
Today, catvirus.com provides links to some of the latest information on FIP. Addie said she also did not foresee that a site she intended for veterinarians would become a reference for pet owners. "It makes sense, though, if you have loved an animal, you'll know that feeling of doing anything to save him or her," she said.
Last autumn, she began charging for consultations with veterinarians and pet owners. She also asks for donations on the site to support her research, which is focused on fighting feline coronavirus, the pathogen that leads in some cats to the development of FIP.
When owners contact her, Addie works with their primary veterinarian before giving a second opinion. "They supply the clinical history and laboratory test results and we make a plan for the patient," she said. Because FIP is rare and many veterinarians have little experience diagnosing and treating it, she sees her role as supporting veterinarians.
"My emphasis is on correct diagnosis: one-third of the patients turn out not to have FIP, so actually have no need of anti-coronaviral drugs," she said.
Addie said she does not actively encourage people to use GC376 or GS-441542, but she will support them if they choose to. She also recommends other treatments — some of them controversial — including antifungals, immunostimulants, anti-inflammatories and feline interferon. She is concerned that these other treatments have gotten lost in the excitement over GS and GC.
That excitement and the growing demand for GS may be hitting a roadblock.
Earlier this month, members of the FIP Warriors Facebook group told VIN News that two suppliers selling versions of GS were shutting down after receiving cease-and-desist letters purportedly from Gilead. One member, who asked not to be identified because she advocates the use of compounds that are illegal in the U.S., said the closures are causing a huge supply shortage. If the letters are not from Gilead, she speculated, they could be from one GS seller hoping to deter another.
VIN News has not seen the letters, which are said to be written in Chinese, nor been able to confirm their origins. Gilead had no comment about them. These developments highlight another aspect of this precarious moment in the lives of FIP-afflicted cats and their owners: Even as a possible cure dawns on the horizon, it may disappear at any moment.
Part 1: Hope, despair fuel black market for drugs in fatal cat disease
Correction: Peter Cohen's cat Smokey was treated with 168 shots of GC376, not 186 shots of GS-441524 as originally reported.