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. Experiments at UC Davis, published in 2018 and 2019, suggest that cats have not only had their lives extended by days or weeks, but that there has been a real cure. "It suddenly changed the whole game," says Drew Weigner, a veterinarian and president of the Winn Feline Foundation, which funded part of UC Davis's research. "Three years ago, we told patients, 'Your cat will die.' Now we can tell them something else. 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 virus replication. They are nucleoside analogues, meaning that they mimic the nucleoside building blocks - A, U, C or G - that make up the genetic material of a virus. Specifically, they mimic block "A". When a virus is thus "cheated" and incorporates a GS-441524 molecule or a remdesivirus instead of an "A" block, its replication process gets stuck. Eventually, it will no longer be possible to add more letters and the virus will not be able to replicate. What makes the two drugs different is that remdesivir has an additional phosphate group that helps it penetrate the cell and adapt to replication. This modification is commonly used to increase the effectiveness of similar antivirals. "It's one of those clever things that really worked perfectly," says Katherine Seley-Radtke, an antivirus 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 out of 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 currently 76 years old and has devoted 50 years of his career to FIP research. Eventually, the drug seemed at hand. "I felt really good," he told me, "and I thought that was a good milestone for my career." However, the peak of my career did not materialize, at least not as he expected. Despite its success, Gilead refused to license GS-441524 for its use in the treatment of 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.
It was difficult for Pedersen to accept this explanation. "It was a blow," he said. "It strikes a lot, especially when he sees no reason to do so." He still published the studies, as academic scholars do, and the results were made 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 drugs from China was at first controversial in the FIP community. "I got a lot of hate mail for that." I lost a lot of supporters, "says Peter Cohen, the first supporter of the drug. Cohen runs ZenByCat, a non-profit organization that raises money for two FIP research funding groups, the SOCK FIP and the Bria Research Fund of the Winn Feline Foundation. Previous iterations of support groups on Facebook, such as FIP Fighters, also initially banned any discussion of drugs on the black market.
Susan Gingrich, the group's former administrator on Facebook, focused on the pressure on Gilead. Gingrich, whose brother is former "House Speaker" Newt Gingrich, is also the founder of the Bria Fund. Her cat Bria died at the FIP in 2005 and in the same year she founded a fund with the help of her brother and husband. "It would be much easier for Gilead to market the drug or allow another entity to market it," he says. Gingrich bought shares in Gilead after initial research GS-441524 proved promising. In June 2019, she wrote a letter to Gilead, as well as to President Donald Trump and her congressman and senators in Tennessee, asking the company to allow the use of the drug for animals. She says she didn't get an answer.
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 lawyer and cat breeder in New York, joined the group in February when her cat Nora turned yellow and stopped eating and her belly swelled like a balloon. Lemesh recognized the symptoms of wet FIP and knew it was a hopeless illness. She was about to call her vet for euthanasia when she came across a group while furiously seeking treatment online. She made an extraordinary request for GS-441524. "I was in contact with someone within 10 minutes," she told me. "After the next two hours, my cat received the first dose." And within a few days, Nora started eating again. She is almost at the end of 84 days of 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 these two personalities in my brain, but it's hard," Lemesh said. On the one hand, there is a cat mother who would try very hard to save her cat; on the other hand, she is a lawyer who focuses on rules and cannot believe that she has injected her cat with an unmarked medicine from a stranger. But if it was between letting Nor die and a small chance to save her, the choice was clear. Of course, Lemesh told me that she would rather go the legitimate path - if there was such a possibility. "Do you think people would like to send $ 7,000 to $ 12,000 to some weird 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 much that Chinese dealers are now approaching the group to launch their GS-441524. Sometimes they appear and then disappear. "It's hard to tell if it's companies or just dealers," says Kintz. However, the group has tried to introduce a degree of responsibility. He is trying to test several popular brands to verify the concentration and content of drugs with GS-441524. When new dealers arrive, the group requests samples to be sent to owners who cannot afford GS-441524 for their cats and who would otherwise certainly die at the FIP. "This is how we generally determine whether it will work and whether it will be okay," says Kintz. However, the group also denies full responsibility as they are unable to validate every particular drug.
Example: This January, a popular drug brand with GS-441524 appeared to be killing the cats to which it was administered. When the group noticed this, administrators began collecting data and warning of the brand's latest series. The man who sold her online disappeared and several members of the group revealed that he still owed them money. It was said that he and his wife went through a divorce; She was having brain surgery, and he tried, but failed to continue the business. Then a new brand GS-441524 appeared - allegedly made by his wife. It is impossible to verify all this from the opposite earth hemisphere. "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."
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