Clinical Testing of GS-441524 for Cats with FIP [AN UPDATE]

1. Introduction

Feline infectious peritonitis (FIP) is a viral disease caused by feline coronavirus (FCoV). This virus is a mutant of feline enteric coronavirus (FeCV) which cannot be easily defeated through a cat's natural immune response. FCoV will infect white blood cells and spread through the cat’s body. The disease is progressive and can be fatal if left unattended. It is estimated that this disease can kill 1.4% of cats around the world.

FIP can be divided into two categories, the effusive (wet) form and the non-effusive (dry) form. Common symptoms of FIP include loss of appetite, fever, depression, and weight loss. Cats can evolve from one FIP form into another form from time to time.

Nucleoside analogue has been found promising in treating both effusive and non-effusive FIP. Professor Pederson and his colleagues discovered that a nucleoside analogue, GS-441524, is effective in treating FIP.[1] Their research published in February 2019 demonstrated that 26 out of 31 cats were recovered from FIP, regardless of the form and age. Additionally, another study by Dickinson and his co-workers has proved that GS-441524 can be used to cure 3 out of 4 cats with neurological FIP.[2]

In our clinical trial, we aimed to reproduce and improve upon the clinical results published by Dr. Pedersen’s research group. Twelve cats participated in our clinical trial. Dosages between 5-10mg/kg of cat’s body weight were given based on the gravity of FIP infection. 11 cats were given our 15mg/ml solution. 1 cat was given our 17mg/ml solution.

1 cat, code F2003W showed progress during the treatment as he gained weight from 2.9kg to 3.5kg. However due to severe liver damage, he was euthanized on doctor’s recommendation.

2 cats code F2001N and F2002N exhibited neurological symptoms prior to the treatment. They began treatment on our 15mg/ml GS-441524, but changed to another brand of GS with higher concentration of 17mg/ml after 20 days. The reason for this decision according to cat’s owners was that the daily injection volume using the 15mg/ml was too high for cats with severe neurological FIP symptoms. We created 17mg/ml solution shortly after learning of their experience.

2 cats F2006O and F2004DN began treatment in late June and have completed only 10 days of treatment as of the time of this report. F2006O exhibited ocular symptoms and F2004DN exhibited neurological symptoms that affected cat’s mobility. Both cats showed noticeable improvements within the first 10 days of treatment using our GS-441524. F2006O gained weight after 2 injections and the infected eye began clearing up. F2004DN mobility improved after 5 injections.

2 cats, news participants are both relapse cases from another brand. They will be begin FIP treatment with our our 17mg/ml GS-441524 starting next week.

5 cats have completed 60 days of treatment. Their progresses are described in details below.

2. Methods

These five FIPV infected cats were of ages range from 0.5 to 96 months. Two of the cats had non-effusive (Dry) FIP (F2010D and F2011D) while the remaining three cats had effusive disease (F2007W, F2008W and F2009W). Among these, F2007W, F2009W and F2011D are of British ShortHair bred while F2008W and F2010D are of European ShortHair Bred. The treatment was conducted at a dosage of 5.0 mg/kg q24h for 12 weeks. Initial blood test was done on cat F2008W, F2010D and F2011D. Another blood test was carried out with F2011D after 25 days of injection. Body weight and temperature were selected as two major indicators of FIPV treatment efficacy using GS-441524 solution.

3. Results and Discussion

3.1. Complete Blood Count (CBC)

Table 1. Blood test results of selected FIPV infected cats.

Table 1 shows that a low A/G ratio is one of the indicators of FIPV infection. As presented, all the cats tested had an initial A/G ratio lower than 0.57 before our GS-441524 treatment. This is attributed to the low serum albumin level and high serum globulin level presented in cats with FIP.[1] After treatment, the A/G ratio increased back to normal range as expected.

Another signal of FIPV infection was higher than normal total protein concentration. Cat F2008W and F2011D were diagnosed with a high total protein concentration of 90 g/L and 94 g/L, respectively. This is slightly higher than the upper limit of normal range. The total protein concentration was dropped back to normal after 25 days of treatment. The decrease in total protein is attributed to the decrease in monocytes and neutrophils concentration, which signals the recovery from FIP.

The blood test results of F2011D indicated that FIP could accelerate the catabolism of red blood cells. This was evidenced by a lower than normal haemoglobin concentration and significantly higher total bilirubin level (hyperbilirubinemia) before treatment. After treatment, both the haemoglobin and total bilirubin levels of F2011D returned and fell within normal range. The haemoglobin level was increased by 31.6% to 125 g/L while total bilirubin level was decreased by 44.4% to 5 μmol/L after 25 days of treatment.

3.2. Weight Change

Figure 1. Weight change of wet FIP cats during treatment.

Figure 2. Weight change of dry FIP cats during treatment.

During the course of treatment, weight gain was observed in both wet and dry FIP cats (Figure 1 and Figure 2). This is due to the regaining of appetite which was lost upon infection. According to study, the cats started to gain weight as early as 5 days. However, as demonstrated by cat F2008W, it was shown that weight gain can be delayed to after 7 days of treatment. Smaller extent of weight gain was also observed in the pregnant cat after labour. The weight of cat F2007W decreased sharply after day 10 due to the birth of kittens. After that, the cat’s weight began to rise and return to 4.9 kg and maintained thereafter.

Comparison between the weight change in wet and dry FIP cats leads to the conclusion that dry FIP cats tend to experience greater extent of weight gain than their wet counterparts.

3.3. Body Temperature

Figure 3

Figure 3. Body temperature of dry FIP cats for the first 28 days of treatment. Normal body temperature of a cat is between 37.7 – 39.1 °C.

The body temperature of the dry FIP cats were monitored to evaluate the effectiveness of GS-441524 treatment. Figure 3 demonstrated that both of the dry FIP infected cats observed were having a higher temperature that close to having a fever. After the beginning of treatment, the body temperature of elder cat F2010D (2 years old) gradually decreases to the normal range and fluctuates within this range. No fever was detected in this cat for the 28 days monitoring period.

In contrast, cat F2011D had lesser fluctuation than the F2010D. Its body temperature remained at the higher end and eventually got a fever between day 8 to day 16. After 15 days of treatment, the cat began to respond to the treatment and its body temperature gradually fell back to normal range in the next few days. The temperature of this cat remains in the normal range for the rest of the monitoring period. This indicates that our GS-441524 solution is effective in treating FIP and resolves fever.

4. Conclusion

In conclusion, the results of five cats that have completed 60 days of our clinical trial demonstrated that our GS-441524 solution is effective in treating effusive (wet) and non-effusive (dry) FIP. Although the participating cats responded at different rates and extent, the medicine proved effective in treating FIP as indicated by an increasing A/G ratio, decreasing total protein to normal range, increasing haemoglobin concentration to normal level, and resolving hyperbilirubinemia and fever in infected cats. Eventually, the recovering cats experienced weight gain due to regaining appetite.

The results of the 7 remaining cats will be published upon the completion of their treatments in an updated version of this report.

5. References

[1] Niels C. Pedersen, Michel Perron, Michael Bannasch, Elizabeth Montgomery, Eisuke Murakami, Molly Liepnieks, and Hongwei Liu, Efficacy and safety of the nucleoside analog GS-441524 for treatment of cats with naturally occurring feline infectious peritonitis, J. Feline Med. Surg. 2019; 271–281.

[2]Peter J. Dickinson, Michael Bannasch, Sara M. Thomasy, Vishal D. Murthy, Karen M. Vernau, Molly Liepnieks, Elizabeth Montgomery, Kelly E. Knickelbein, Brian Murphy, Niels C. Pedersen, Antiviral treatment using the adenosine nucleoside analogue GS ‐441524 in cats with clinically diagnosed neurological feline infectious peritonitis, J. Vet. Intern. Med. 2020; 1-7.

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