Summary of GS 441524 treatment for FIP 

Summary of GS 441524 treatment for FIP


Niels C. Pedersen, DVM PhD, Distinguished Professor Emeritus  

Center for Companion Animal Health  

School of Veterinary Medicine, UC Davis  


We use the same criteria for monitoring treatment as described in the JFMS field trial paper.  Owners are asked to keep track of temperature, weight, activity, appetite, clinical signs of original  disease at daily or weekly intervals. Blood tests including at a minimum CBC (hemogram) and serum  chemistry panel (including serum protein values -total protein, albumin, globulin, A:G ratio) at onset  of treatment and every 4 weeks thereafter. It is always helpful when these values, along with  weight, are updated in a graph form. The goal is to have a health, alert and active cat at the end of  12 weeks of treatment and with normal blood test values, especially for hematocrit, total protein,  globulin, albumin and A:G ratio. A significant weight gain is also a good sign and some young or  particularly wasted cats can more than double their weight during their treatment. Of course, this is  an idealized treatment, and one must expect that dosage may need to be adjusted upward if  response is slow or if complications such as ocular or neurological involvement should manifest  during treatment.


Supportive (symptomatic) care may be needed to stabilize cats that are critically ill at the time of  diagnosis or during the first few days of GS-441524 (GS) treatment. Abdominal effusion should not  be removed unless it is compressing the chest and interfering with breathing, as it will just be  rapidly replaced at the expense of the rest of the body. However, thoracic effusions are usually  associated with varying degrees of dyspnea and should be removed. Thoracic effusions are much  slower to recur. Symptomatic care also frequently includes fluids and electrolytes to counteract  dehydration, antibiotics when a secondary bacterial infection is suspected, and anti-inflammatories  (usually systemic corticosteroids), and rarely blood transfusion. Topical medications may also be  needed to counteract severe inflammation and increased intraocular pressure (glaucoma) in some  of the cats with ocular involvement.  


Corticosteroids such as prednisolone should only be used for the first few days of GS treatment and  then discontinued as rapid improvement in health occurs. Long-term use of corticosteroids with GS  is strongly discouraged as it can mask improvement signs caused by the GS, especially in cats with  neurological FIP, it has no curative power, and may interfere with the development of a protective  immune response to the FIP virus. It is possible that this immune response plays a major role in the  ultimate cure. If cats are on chronic steroid treatment, there is no need in cats to taper the dosage  as there is no evidence that severe adrenal atrophy, such as occurs in humans on long-term steroid  treatment, occurs in cats. Many owners, GS treatment advisors, and veterinarians will use various  supplements advertised to improve liver, kidney or immune system health as well as vitamins such  as B12. These substances have no proven efficacy and I consider them a waste of money. 


The treatment with the injection form of GS, which is most common, can also be complicated by  injection site sores. The treatment is also hard on both owners and cats, as injections can be  painful. There is also a problem in some cats, especially those with neurological involvement, with development of partial drug resistance, which requires an increasing dosage. Response to  treatment is usually within 24-72h and most cats are back to normal or near normal within 2-4  weeks, which is a good sign. We feel that the cure rate for FIP with GS-441424 is over 80%, with  treatment failures due to misdiagnosis of FIP, inadequate dosage, complicating disease conditions,  and drug resistance. Young cats are easier to treat and have a higher cure rate than old cats >7  years of age, cats with wet or dry FIP not complicated by neurological or ocular disease are easier to  cure than cats with neurological FIP.  


The starting dosage for cats with wet or dry FIP and no ocular or neurological disease signs is 4-6  mg/kg daily for 12 weeks, with the younger and wet cases tending to go toward the lower end and  the dry cases toward the higher end. Cats with ocular lesions and no neurological signs start at 8  mg/kg daily for 12 weeks. Cats with neurological signs start at 10 mg/kg, daily for 12 weeks. If cats  with wet or dry FIP at the beginning develop ocular or neurological signs they go to the appropriate  ocular or neurological dosage. There is an oral form of GS available from at least two sources out of  China (Aura, Mutian) and I do not use it so am not familiar with the comparable dosage. However, I  do not recommend it when the injectable dosage goes above 10 mg/kg daily, as the efficiency of  oral absorption goes down at these high dosages.  


I recommend that the dosage be adjusted with weekly weight checks. Weight gain can be  tremendous in many of these cats, either because they are so wasted at the start or that they are  growing, and/or both. If there is some weight loss at first of treatment, I stay at the original dosage  and do not lower it. Failure to gain a good amount of weight during treatment is considered a bad  sign. I do not raise a dosage unless there are significant reasons to do so, such as failure or blood  tests to improve, slow improvement, poor activity levels, failure of original clinical signs to  disappear, or change in disease form to include ocular or neurological signs. This is where the art  comes into play, because you do not want to get stuck on single blood values that are not quite  normal and neglect the overall health status of the cat. For example, the globulin may still be a little  high, but other critical blood test values and health status are good. If there is significant reason to  increase the dosage, it should always be from +2 to +5 mg/kg daily and for a minimum of 4 weeks. If  4 weeks extends the 12-week treatment time, the treatment time is extended to accommodate.  One should expect a positive response to any increase in the dosage and a failure to see  improvement indicates that the dosage is still not high enough, drug resistance is occurring, the  brand of GS is not what it should be, the cat does not have FIP, or there are other diseases  confusing the treatment.  


One of the most difficult decisions is to determine when to stop treatment. Although some cats,  often younger ones with wet FIP, can be cured in as little as 8 weeks and possibly sooner, the usual  treatment time is 12 weeks. Some cats may even require dosage adjustments and even longer  treatment periods. Critical blood values such as hematocrit, total protein, albumin and globulin  levels, and total WBC and absolute lymphocyte counts usually normalize in cats destined for cures  at 8-10 weeks, at which time there is often an unanticipated increase in activity levels. It is believed,  but not proven, that 8-10 weeks in when the cat’s own immunity to the infection occurs. This is a  situation that occurs with hepatitis C treatment in people, which is also a chronic RNA virus  infection that often requires up to 12 weeks or more of antiviral drug treatment. 


Unfortunately, there is no simple test that will determine when a cure has occurred and the fear of  relapse often drives owners, treatment advisors, and veterinarians to extend treatments beyond 84  days. Fear of relapses will also cause those people involved in the decision process to be overly  cautious about single blood values that are a little abnormal (e.g., slightly high globulin or slightly  low A:G ratio), or terminal ultrasound findings suggesting suspiciously enlarged abdominal lymph  nodes, small amounts of abdominal fluid, or vague irregularities in organs such as the kidneys,  spleen, pancreas, or intestines. It must be remembered that a normal range for a blood value  covers most animals, but that it is a bell-shaped curve and that there will be a few exceptional  patients that will have values on the margins of these curves. Ultrasonographers need to consider  the degree of pathology that can occur in a FIP diseased abdomen and how scarring and other  residual effects can alter normal appearances in successfully treated cats. In situations where such  questions arise, it is best to look more closely at the total picture and not just one small part. The  most important result of treatment is the return to normal health, which has two components – outward signs of health and inward signs of health. Outward signs of health include a return to  normal levels of activity, appetite, appropriate weight gain and/or growth, and quality of the coat.  The latter is often one of the best measures of health for a cat. Inward signs of health are  manifested by a return to normal of certain critical values based on periodic complete blood counts  (CBC) and serum chemistry profiles. The most important values in the CBC are the hematocrit and  the relative and absolute total white blood cell, neutrophil and lymphocyte counts. The most  important values in the serum chemistry panel (or serum electrophoresis panel) are the levels of  total protein, globulin, albumin, and the A:G ratio. Bilirubin is often elevated in cats with effusive  FIP and can be useful in monitoring the severity and duration of the inflammation. There are many  other values in a CBC and serum chemistry panels, and it is not unusual for some of them to be a  little higher or lower than normal, and it is best to ignore these values unless they are significantly  elevated and associated with clinical signs. For instance, a high BUN and Creatinine that is also  associated with increased water consumption, excess urination, and abnormalities in the urinalysis.  Platelet counts by machine are notoriously low in cats due to trauma from blood collection and  platelet clumping and should always be verified by manual examination of the blood smears. The  final decision to stop or extend treatment when confronted with vague doubts from various test  procedures should always be based on the outward manifestations of health more than any single  test result.  


Various modifications in the treatment have been created by different FIP treatment groups. Some  groups will treat with an exceedingly high dosage of GS from the onset rather than escalating the  dosage only when indicated, or cap off the treatment during the last two weeks or in an added two  weeks with a higher dosage of GS on the hope that it may reduce treatment time or the chances of  relapse. Some advocate the use of interferon omega or non-specific immunostimulants to further  stimulate the immune system, and some employ even different modifications. There is no evidence  that capping the treatment with an extra high dosage will improve cure rates. Likewise, interferon  omega and non-specific immunostimulants have no proven beneficial effects on FIP when given as  sole treatments or as supplements to GS. The practice of adding another antiviral drug, GC376 viral  protease inhibitor, to GS treatment in cats developing GS resistance is also emerging and needs  research. Finally, it is common for owners, treatment groups, and veterinarians to add in many  supplements, tonics, or injections (e.g., B12) to bolster blood levels or prevent liver or kidney  disease. Such supplements are rarely necessary in cats with pure FIP disease. 


Relapses of FIP during the 12-week post-treatment observation period do occur, and there is no  simple blood test to predict when a cure has occurred or if a relapse will occur. Relapses usually  involve infections that have escaped to the central nervous system (brain, spine, eyes) during  treatment for wet or dry FIP not accompanied by neurological or ocular signs. The dosage of GS 441524 used to treat these forms of FIP are often insufficient to effectively overcome the blood-to brain or blood-to-eye barriers. The blood-to-brain barrier is even more effective than the blood-to eye barrier, which explains why eye lesions can be more easily cured than brain and/or spinal  infections. Relapses that occur in the post treatment period, and that involve, eyes, brain or spine  are usually retreated for at least 8 weeks at a starting daily dosage at least 5 mg/kg higher that the  dosage used during the primary treatment (e.g., 10, 12, 15 mg/kg daily). It is recommended that  oral forms of GS not be used when the dosage exceeds 10 mg/kg daily of the injectable form, as the  efficiency of gut absorption is diminished at high oral concentrations. Cats that cannot be cured of  infection at dosages of as high as 15 mg/kg daily are likely to have developed varying degrees of  resistance to GS-441524. Partial resistance may allow for control of disease signs, but not a cure,  while total resistance is manifested by varying severity of clinical signs in the face of treatment.  


Resistance to GS-441524 can exist at the time of diagnosis, but this is uncommon. Rather, it tends  to occur during treatment and is often partial at first and necessitates a higher dosage to  accommodate for it. It can become total in some cats. Resistance is the biggest problem in cats with  neurological disease, especially those that present with neurological disease or develop brain  infections during treatment or during a relapse after what appears to have been a successful  treatment. Many cats with partial drug resistance can be treated for their disease signs but will  relapse as soon as the treatment is stopped. There have been cats “treated” for FIP for over a year  with no cure, but ultimately resistance becomes worse, or the owner runs out of money.  GS-441524 treatment is amazingly free of systemic side effects. It can cause minor kidney damage  in some cats, but this does not progress to overt renal disease. Systemic drug reactions of the  vasculitis type have been seen in a few cats and can be confused with injection site reactions.  However, these drug reactions are at non-injection sites and are often self-limiting or respond well  to a short-term low dose of steroids. The major side-effect of GS treatment is pain at the injection  sites, which varies from cat to cat and according to the injection prowess of the person doing the  treatment (usually the owner). Injection site sores are a problem with some owners and usually  occur when the injection site is not moved around the body (stay away from between the  shoulders) and not given into the muscle and nerve layers below the subcutis. I recommend  selecting sites starting an inch behind the shoulder blades, down the back to 1-2 inches before the  tailhead, and one third to one-half of the way down the chest and abdomen. Many people use  gabapentin before injections to help ease the pain. Injection site sores are cleared of surrounding  hair and gently cleaned 4 or more times a day with sterile cotton balls soaked in 1:5 dilution of  household hydrogen peroxide. They usually do not require any more sophisticated treatment and  heal within 2 weeks or so.  


The current hope is that a legal form of GS-441524 will be soon available. A drug named Remdesivir  is the best current hope, because Remdsivir it is immediately broken down to GS when  administered intravenously in humans, mice, primates and cats. Remdesivir has been given full  approval by the US FDA and similar approval will probably follow in other countries. If so, it can be  prescribed by any licensed human physician, and by default, by veterinarians. However, the use of  Remdesivir in the US has been still limited to a specific subset of Covid-19 patients and only under controlled conditions and with continued data collection. Until all restrictions are lifted, it will not  be readily available for even human use. I have no experience with treating cats with Remdesivir  instead of GS-441524. However, groups in Australia and some Asian countries are starting to use it  and report identical results to GS-441524. The dosage of Remdesivir on a molar basis is theoretically  the same as GS-441524. The free base form of GS-441524 has a molecular weight of 291.3 g/M,  while Remdesivir is 602.6 g/M. Therefore, it would take twice as much Remdesivir  (602.6/291.3=2.07 mg) to yield 1 mg of GS-441524. The diluent for Remdesivir is significantly  different than the diluent used for GS-441524 and designed for IV use in humans. How diluted  Remdesivir will behave when injected subcutaneously over 12 or more weeks of daily treatment is  not known. Finally, mild signs of both liver and kidney toxicity have been seen with Remdesivir in  humans. GS-441524 causes mild and non-progressive renal toxicity in cats but with no apparent  liver toxicity. It is uncertain whether the renal toxicity seen in humans given Remdesivir is due to its  active ingredient (i.e., GS-441524) or to the chemical additions meant to enhance antiviral activity.  GC376 approval for cats (and humans) is in progress by Anivive but is still two or more years away.  GC376 is a viral protease inhibitor and works downstream from GS-441524, which inhibits the  earliest stage of viral RNA replication. Therefore, it is unlikely to have a significant synergistic viral  inhibitory effect and will be much more important in inhibiting drug resistance when used in  combination (such as in combination antiviral therapy for HIV/AIDS.


Revised – 11.10.2021



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