Cat owners are resorting to the Chinese black market to buy antiviral drugs for cat coronavirus.
SARAH ZHANG
MAY 8, 2020
Original article: A Much-Hyped COVID-19 Drug Is Almost Identical to a Black-Market Cat Cure
When both Robin Kintz-Fiona and Henry kittens contracted a deadly disease last year, she received reports of a drug from the Chinese black market. The use of the drug known as GS-441524 is based on UC Davis' legitimate research, but the ways to obtain it were no longer so legitimate. It was, "If you want to save your cat, send me thousands of dollars and I'll give you some unmarked vials through DHL," he says. And she did. Robin Kintz transferred thousands of dollars, received unmarked vials from China, and then applied clear fluid to the bodies of her dying cats for months.
The first noteworthy thing about the nature of the transaction is that the drugs actually worked. Henry lived almost another year, and Fiona fully recovered. Still cupped wherever she can, she is soft and alive - a miracle when we realize that veterinarians have long thought that her disease, infectious peritonitis in cats, is incurable and one hundred percent fatal. Kintz now runs a 22,000-member Facebook group that helps cat owners use the GS-441524. Thousands of cats were reportedly cured of the FIP.
The second notable thing is that GS-441524 is almost identical to the human drug so much talked about today: remdesivir, the antiviral agent that is currently our best hope for treating COVID-19, a disease caused by a new coronavirus. Although initial data suggests that the drug shortens recovery time at best, Anthony Fauci promoted a White House remdesivir. The Food and Drug Administration has approved its emergency use. And Gilead Sciences, which makes remdesivir, is donating 1.5 million doses of the drug during the pandemic.
Gilead also developed and patented GS-441524. Its researchers have co-authored studies by UC Davis that show its effectiveness against FIP. However, the company refused to license GS-441524 for use in animals for fear that its resemblance to remdesivir could interfere with the FDA approval process for medicinal products for human use - originally intended for the treatment of Ebola. When this failed, and later came the global pandemic of the new coronavirus, the company began testing it against COVID-19. Remdesivir has a small but sophisticated modification that facilitates cell entry, but together with GS-441524 they have exactly the same mechanism of action.
FIP is also caused by a coronavirus - not one that causes COVID-19, but one that specializes in infecting cats. (Although humans may in rare cases pass COVID-19 to cats, humans cannot receive FIP from cats.) In most cats, this feline coronavirus or FCoV causes mild diarrhea or no symptoms at all. But in a small minority of cases, the virus infects white blood cells, and FIP breaks out fully in the immune system. The disease has two forms, and both are fatal: wet, when the cat's chest or abdomen is filled with fluid, or dry, which lacks effusion but the cat has fevers and eventually dies. For decades, veterinarians have been unable to offer anything but euthanasia.
Then came GS-441524. UC Davis trials published in 2018 and 2019 suggest that cats not only lived longer by days or weeks, but were actually cured. “It was a game-changer,” says Drew Weigner, a veterinarian and president of the Winn Feline Foundation, which funded part of the UC Davis research. “Three years ago, we were telling patients, ‘Your cat is going to die.’ Now we can tell them something different. It’s an interesting story.”
The story of a drug that was first tested against Ebola (where it failed), whose close cousin has become a groundbreaking treatment for fatal cat disease (but only illegally), and which was resurrected in a completely new virus pandemic, underscores drug development. While remdesivir has undergone clinical trials, GS-441524 has not been tested in humans for safety or efficacy against COVID-19. GS-441524 products on the black market are also incredibly expensive. A 12-week treatment for a cat can cost up to $ 10,000, depending on the brand, type of FIP and weight of the cat. In addition, there is no legal way to buy GS-441524 as a medicine - neither for cats nor for humans.
The drug would probably never have been tested on cats without the fact that Niels Pedersen, a longtime FIP researcher at UC Davis, had personally met a former Gilead executive. The two met 30 years ago when Gilead tested antiviral drugs for HIV in monkeys and Pedersen worked at a research center for primates. But Pedersen's real love has always been cats. He grew up surrounded by cats on a poultry farm. His colleague lovingly warned me that Pedersen was "irritable" and difficult to catch on the phone. But his voice softened as he talked about domesticating those cats in the barn and finding homes for their kittens.
Pedersen was fascinated by FIP while studying veterinary medicine in the 1960s, when it was still a mysterious disease with a mysterious cause. Over the decades, researchers discovered that FIP caused feline coronavirus, and then spent years trying again, but failed to develop a functional vaccine. Pedersen eventually devoted his entire career to researching the disease. When all the vaccines failed, he began to think about antivirals and think again about Gilead. The California company specializes in the development of antivirals, including Tamiflu, Truvada and many drugs for HIV and hepatitis C.
About five years ago, Pedersen contacted his contact at Gilead, and the company sent him 25 or 30 molecules from the large library of drug candidates that pharmaceutical companies usually maintain. Two of the molecules have been shown to be miraculously effective in FIP virus-infected cat cells: GS-441524 and GS-5734, the latter of which is better known today as remdesivir.
Both GS-441524 and remdesivir block viral replication. They are nucleoside analogs, meaning they mimic the nucleoside building blocks—A, U, C, or G—that make up the virus’s genetic material. Specifically, they mimic the “A” block. When a virus is tricked into incorporating a GS-441524 or remdesivir molecule instead of the “A” block, its replication process gets stuck. Eventually, no more letters can be added, and the virus can’t replicate. Where the two drugs differ is that remdesivir has an extra phosphate group that helps it enter cells and adapt to replicate. This modification is commonly used to boost the effectiveness of similar antivirals. “It’s one of those clever things that really worked perfectly,” says Katherine Seley-Radtke, an antiviral researcher at the University of Maryland in Baltimore County.
However, for some reason, this modification did not cause a difference in their effect in FIP-infected cat cells. Both molecules were effective, so Pedersen decided to continue the simpler one, GS-441524. He infected 10 FIP cats and gave them GS-441524. All 10 cats recovered.
“We almost fell off our chairs,” says Weigner. That is funny , he recalls. This may not work well. Wait, wait, stop, come back? What has happened? The initial study was small and under artificial conditions, but in a subsequent rigorous trial of 31 pets with naturally occurring FIP, 25 cats fully recovered at an unprecedented rate. Pedersen had previously tested another antiviral drug at Kansas State University, but only seven of the 20 cats were in remission. These results seemed impressive at the time, but GS-441524 appeared to be even better.
Pedersen is now 76 years old and has spent 50 years of his career researching FIP. Finally, a cure seemed within reach. “I felt really good,” he told me, “and I thought it was a good milestone for my career.” But the pinnacle of my career didn’t happen, at least not in the way he had hoped. Despite its success, Gilead refused to license GS-441524 for use in cats.
While Pedersen tested GS-441524 on cats, on the other side of the world, another virus raged in West Africa - the human virus: Ebola. The virus that causes Ebola is not a coronavirus, but remdesivir is an antiviral drug with a broad spectrum of action, and the first results against Ebola were promising. In fact, so promising that the company was considering FDA approval regarding remdesivirus in humans.
According to Pedersen, Gilead feared that cat research could hinder the remdesivir approval process. Because GS-441524 and remdesivir are so similar, it may be necessary to report and investigate any side effects found in cats to ensure the safety of remdesivir in humans. Gilead's best practice in generating unnecessary cat data is standard industry practice. "One of the rules when developing drugs is to never take a test that you don't have to do if the results could be problematic," says Richard Sachleben, a retired pharmaceutical researcher. Gilead declined to comment on the story.
Pedersen found the explanation difficult to accept. “It was a blow,” he said. “It hits you hard, especially when you don’t see any reason for it.” He continued to publish the studies, as academics do, and the results became public in 2018 and 2019.
Shortly afterwards, Pedersen heard from certain people in China that one company wanted to buy the drug from Gilead. She asked Pedersen to be a mediator. Although the company did not obtain a license, it still started selling the drug at FIP and its exact formula is unclear. Other companies explicitly advertise their formulations as GS-441524. China has a large pharmaceutical production base and the synthesis of crude GS-441524 is not particularly demanding. FIP is also a growing problem in the country as cats - especially purebred cats, which are more susceptible to the disease - are becoming increasingly popular in China. A black market emerged that filled the vacuum left by Gilead.
The use of the Chinese drug was initially controversial in the FIP community. “I got a lot of hate mail for it. I lost a lot of supporters,” says Peter Cohen, an early supporter of the drug. Cohen runs ZenByCat, a nonprofit that raises money for two groups that fund FIP research, SOCK FIP and the Winn Feline Foundation’s Bria Fund for FIP Research. Previous iterations of Facebook support groups, such as FIP Fighters, also initially banned any discussion of black-market drugs.
Susan Gingrich, a former administrator of the Facebook group, has focused her efforts on pressuring Gilead. Gingrich, whose brother is former House Speaker Newt Gingrich, is also the founder of the Bria Fund. Her cat, Bria, died of FIP in 2005, and she started the fund that same year with the help of her brother and her husband. “It would have been a lot easier if Gilead had marketed the drug or allowed someone else to market it,” she says. Gingrich bought Gilead stock after early research on GS-441524 showed promise. In June 2019, she wrote a letter to Gilead, as well as to President Donald Trump and her Tennessee congressman and senator, imploring the company to approve the drug for use in animals. She says she has not received a response.
When Kintz tried to save Fiona and Henry, she asked about GS-441524 in one of those Facebook groups that banned the discussion about the drug. Her contribution to the group led nowhere, but two women privately sent her advice. Kintz eventually formed a new group, now called FIP Warriors, so that its members could exchange tips and feedback on various brands of drugs. The group has grown to 22,000 members on Facebook - as well as 25 administrators and 26 moderators. It has satellite groups in various countries and languages around the world. "We sometimes feel like a global company," says Kintz, a design consultant in New York State. If he is offline, say six hours, he will notify his fellow administrators and moderators. Facebook has become a non-stop international organization.
FIP Warriors also has a network of emergency group chats for each state. Because transportation from China can take a long time and because the sooner GS-441524 treatment begins, the better, the emergency huts connect the new members with those who have free injection vials with GS-441524.
Zina Lemesh, a New York City lawyer and cat breeder, joined the group in February when her cat, Nora, turned yellow and stopped eating, her belly swelling like a balloon. Lemesh recognized the symptoms of wet FIP and knew it was a hopeless disease. She was about to call her vet about euthanasia when she came across the group while frantically searching online for a treatment. She filed an emergency request for GS-441524. “I was in touch with someone within 10 minutes,” she told me. “Within two hours, my cat had received its first dose.” And within a few days, Nora was eating again. She’s almost at the end of her 84-day treatment. Her swollen belly is completely gone.
“This is a cat mom and a lawyer talking at the same time, and I’m trying to balance those two personalities in my brain, but it’s hard,” Lemesh said. On one side is the cat mom who would be very keen to save her cat; on the other side is the lawyer who is focused on the rules and can’t believe she injected her cat with an unlabeled drug from a stranger. But if it was between letting Nora die and the slim chance of saving her, the choice was clear. Of course, Lemesh told me she would rather go the legitimate route — if there was such an option. “Do you think people would want to send $7,000 to $12,000 to some strange entity?” she said. “Or would they rather pay their vet?”
The availability of GS-441524 on the black market makes it harder for veterinarians. They cannot prescribe the drug or buy it legally for cat owners. Some agree to help owners with injections that can be difficult and painful for a cat. But others do not want anything to do with an unapproved drug. Linda Pendergrass-Nethery, who lives in Chattanooga, Tennessee, told me she had to change her vet. According to her, her first veterinarian refused to help. The other prescribed sedative gabapentin to cure his cat Sundance with injections. So every afternoon, a few hours before the daily Sundance injection, Pendergrass-Nethery and her husband gave him a dose of gabapentin. When the time came, they wrapped him in a white towel - "like a mummy," she said - and stabbed him with GS-441524. It's definitely a job for two people.
Meanwhile, FIP Warriors has grown so large that Chinese vendors are now approaching the group to market their GS-441524. Sometimes they appear and then disappear. “It’s hard to tell if they’re companies or just dealers,” Kintz says. But the group has tried to establish some level of accountability. It’s trying to test a few popular brands to verify the concentration and content of the drugs with GS-441524. When new vendors come forward, the group asks for samples to send to owners who can’t afford GS-441524 for their cats, who would otherwise surely die of FIP. “That’s how we generally determine whether it’s going to work and whether it’s going to be okay,” Kintz says. But the group also declines full responsibility, since it can’t verify every specific drug.
Case in point: This January, a popular brand of GS-441524 medication seemed to be killing cats given it. When the group noticed, the administrators began collecting data and warning about the brand’s latest batch. The man selling it online disappeared, and several members of the group posted that he still owed them money. It was said that he and his wife had gone through a tumultuous divorce; she was the brains of the operation, and he tried but failed to keep the business going. Then a new brand of GS-441524 appeared—supposedly made by his wife. It’s impossible to verify all of this from the other side of the world. “It’s really like the Wild West,” says Kintz.
The recent increase in interest in remdesivir could change some of this momentum. After studies with Ebola proved to be of little use, remdesivir became a cure for another (human) disease. If remdesivirus is properly FDA approved beyond the emergency use for COVID-19, and if it is common to prescribe and distribute it through a pharmacy, veterinarians could legally use it for cats. "It may be five years since COVID may be a distant memory, and then it may be able to be used for FIP," says Weigner. At least for now, there is a lack of data on remedivirus for cats.
Kintz hopes that GS-441524 may one day be legally available to cats. At the same time, he says: "No one would need me anymore, but that's okay."
We want to hear what you think about this article. Write to the editor or write to letters@theatlantic.com.
EN 
SK